Lung Cancer

Antibody-drug conjugates (ADC) link a tumor-targeted antibody to a cytotoxic drug through a chemical linker and hold the promise of high potency. This has led to a burgeoning interest in solid tumors, with over 100 clinical trials in progress. Non–small cell lung cancer (NSCLC) is no exception. In 2022, the Food and Drug Administration approved trastuzumab DXd for pretreated NSCLC patients with HER2-mutant tumors. Two others have lung cancer breakthrough therapy designations from the FDA, including patritumab deruxtecan (HER3-DXd) for EGFR-mutant NSCLC and telisotuzumab vedotin for NSCLC that overexpresses c-Met.

At the annual World Conference on Lung Cancer, researchers outlined some of the latest developments in ADCs targeting the antigens HER3, trophoblast cell-surface antigen 2 (TROP-2), and the B7-H3 immunoregulatory protein, as single agents or in combination with immunotherapy. Following the presentations, discussant Helena Linardou, MD, PhD, emphasized the need for pharmacogenomics to predict toxicity and studies to understand resistance mechanisms. “ADCs are a new, rapidly evolving class of therapeutics, and I think that we will all have to be prepared for the future that is coming,” said Dr. Linardou, who is director of the 4th oncology department and the Comprehensive Clinical Trials Center at Metropolitan Hospital in Athens.

Researchers presented four ADC clinical trial updates.
 

Patritumab deruxtecan

Patritumab deruxtecan (Daiichi Sankyo) links a HER3 antibody to the topoisomerase I inhibitor deruxtecan (HER3-DXd). In the open-label, phase 2 HERTHENA-Lung01 trial, it was tested in patients with NSCLC EGFR-activation mutations, which occurs in 14%-38% of NSCLC cases. There are few options for these patients following failure of EGFR tyrosine kinase inhibitor therapy.

The study included 225 patients previously treated with EGFR tyrosine kinase inhibitors and platinum-based chemotherapy who received 5.6 mg/kg of HER3-DXd every 3 weeks. Over a median follow-up of 13.1 months and a median treatment duration of 5.5 months), 29.8% had a confirmed overall response (95% confidence interval, 23.9%-36.2%) with a median duration of 6.4 months (95% CI, 4.9-7.8). The median progression-free survival was 5.5 months (95% CI, 5.1-5.9), and the median OS was 11.9 months (95% CI, 11.2-13.1). The researchers noted similar outcomes among patients with different mechanisms of EGFR TKI resistance. The frequency of adverse events was similar to previous studies, with drug-related adverse events linked to treatment discontinuation of 7.1% interstitial lung disease in 5.3%. Among 30 patients with brain metastases, the confirmed intracranial response rate was 33.3% (95% CI, 17.3%-52.8%).

The study was published simultaneously online in the Journal of Clinical Oncology. (Abstract)
 

Datopotamab deruxtecan

PD-1/PD-L1 inhibitors are the first-line therapy for metastatic NSCLC, but there are efforts to improve outcomes through combination therapy. Datopotamab deruxtecan (Dato-DXd, Daiichi Sankyo, AstraZeneca) is an ADC targeting TROP2, and it has been shown in preclinical studies to enhance tumor responses to PD-1/PD-L1 inhibitors. The ADC improved progression-free survival (PFS), compared with docetaxel, in previously treated advanced or metastatic NSCLC.

In an interim analysis of the phase 1b TROPION-Lung04 study, researchers reported results from the combination of Dato-DXd with durvalumab with or without carboplatin. The study included 38 patients, some of whom had previously undergone treatment with immune checkpoint inhibitors. Nineteen patients received the doublet, and 14 received the carboplatin triplet. Grade 3 or higher treatment-emergent adverse events occurred in 42.1% of the doublet group and 71.4% of the triplet group. Interstitial lung disease occurred in 15.8% and 7.1% of the two groups, respectively. The objective response rate was 50.0% in the doublet group and 76.9% in the triplet group. The disease control rate was 92.9% and 92.3%, respectively. Durable responses occurred in both the first-line setting and the overall population. (Abstract)
 

Sacituzumab govitecan

Another ADC being tested with PD-1/PD-L1 inhibitors is sacituzumab govitecan (Trodelvy, Gilead), which has already received FDA approval for metastatic triple-negative breast cancer, pretreated HR+/HER2- metastatic breast cancer, and metastatic urothelial cancer. Like datopotamab, sacituzumab targets TROP-2. Researchers reported preliminary results from the phase 2 EVOKE-02 study, in which the ADC was combined with pembrolizumab for the first-line treatment of metastatic NSCLC. The overall response rate was 56% (95% CI, 42%-69%). Among patients with PD-L1 tumor proportion score (TPS) ≥ 50%, the ORR was 69% (95% CI, 49%-85%) and 44% (95% CI, 26%-62%) among those with TPS < 50%. The disease control rate was 86% (95% CI, 68%-96%) and 78% (95% CI, 60%-91%), respectively. The most frequent treatment-emergent adverse events (TEAEs) were diarrhea, anemia, and asthenia, and 18% of patients discontinued the study drug because of TEAEs. (Abstract)

Ifinatamab deruxtecan

Ifinatamab deruxtecan (Daiichi Sankyo) targets the B7-H3 antigen, which is an immunoregulatory protein that is overexpressed in many tumors. In the DS7300-A-J101 study, it was tested in patients with advanced or metastatic solid tumors, without selection for B7-H3 expression. A subgroup analysis of 22 patients with small cell lung cancer (SCLC) showed an ORR of 52.4 (95% CI, 29.8-74.3), a complete response of 4.8%, and a partial response in 47.6%. The median PFS was 5.6 months (95% CI, 3.9-8.1) and median OS was 12.2 months (95% CI, 6.4-not applicable). The most common treatment-emergent adverse events were nausea (59.1%), fatigue (50.0%), anemia (27.3%), vomiting (27.3%), and decreased appetite (22.7%). (Abstract)

Antibody-drug conjugates (ADC) link a tumor-targeted antibody to a cytotoxic drug through a chemical linker and hold the promise of high potency. This has led to a burgeoning interest in solid tumors, with over 100 clinical trials in progress. Non–small cell lung cancer (NSCLC) is no exception. In 2022, the Food and Drug Administration approved trastuzumab DXd for pretreated NSCLC patients with HER2-mutant tumors. Two others have lung cancer breakthrough therapy designations from the FDA, including patritumab deruxtecan (HER3-DXd) for EGFR-mutant NSCLC and telisotuzumab vedotin for NSCLC that overexpresses c-Met.

At the annual World Conference on Lung Cancer, researchers outlined some of the latest developments in ADCs targeting the antigens HER3, trophoblast cell-surface antigen 2 (TROP-2), and the B7-H3 immunoregulatory protein, as single agents or in combination with immunotherapy. Following the presentations, discussant Helena Linardou, MD, PhD, emphasized the need for pharmacogenomics to predict toxicity and studies to understand resistance mechanisms. “ADCs are a new, rapidly evolving class of therapeutics, and I think that we will all have to be prepared for the future that is coming,” said Dr. Linardou, who is director of the 4th oncology department and the Comprehensive Clinical Trials Center at Metropolitan Hospital in Athens.

Researchers presented four ADC clinical trial updates.
 

Patritumab deruxtecan

Patritumab deruxtecan (Daiichi Sankyo) links a HER3 antibody to the topoisomerase I inhibitor deruxtecan (HER3-DXd). In the open-label, phase 2 HERTHENA-Lung01 trial, it was tested in patients with NSCLC EGFR-activation mutations, which occurs in 14%-38% of NSCLC cases. There are few options for these patients following failure of EGFR tyrosine kinase inhibitor therapy.

The study included 225 patients previously treated with EGFR tyrosine kinase inhibitors and platinum-based chemotherapy who received 5.6 mg/kg of HER3-DXd every 3 weeks. Over a median follow-up of 13.1 months and a median treatment duration of 5.5 months), 29.8% had a confirmed overall response (95% confidence interval, 23.9%-36.2%) with a median duration of 6.4 months (95% CI, 4.9-7.8). The median progression-free survival was 5.5 months (95% CI, 5.1-5.9), and the median OS was 11.9 months (95% CI, 11.2-13.1). The researchers noted similar outcomes among patients with different mechanisms of EGFR TKI resistance. The frequency of adverse events was similar to previous studies, with drug-related adverse events linked to treatment discontinuation of 7.1% interstitial lung disease in 5.3%. Among 30 patients with brain metastases, the confirmed intracranial response rate was 33.3% (95% CI, 17.3%-52.8%).

The study was published simultaneously online in the Journal of Clinical Oncology. (Abstract)
 

Datopotamab deruxtecan

PD-1/PD-L1 inhibitors are the first-line therapy for metastatic NSCLC, but there are efforts to improve outcomes through combination therapy. Datopotamab deruxtecan (Dato-DXd, Daiichi Sankyo, AstraZeneca) is an ADC targeting TROP2, and it has been shown in preclinical studies to enhance tumor responses to PD-1/PD-L1 inhibitors. The ADC improved progression-free survival (PFS), compared with docetaxel, in previously treated advanced or metastatic NSCLC.

In an interim analysis of the phase 1b TROPION-Lung04 study, researchers reported results from the combination of Dato-DXd with durvalumab with or without carboplatin. The study included 38 patients, some of whom had previously undergone treatment with immune checkpoint inhibitors. Nineteen patients received the doublet, and 14 received the carboplatin triplet. Grade 3 or higher treatment-emergent adverse events occurred in 42.1% of the doublet group and 71.4% of the triplet group. Interstitial lung disease occurred in 15.8% and 7.1% of the two groups, respectively. The objective response rate was 50.0% in the doublet group and 76.9% in the triplet group. The disease control rate was 92.9% and 92.3%, respectively. Durable responses occurred in both the first-line setting and the overall population. (Abstract)
 

Sacituzumab govitecan

Another ADC being tested with PD-1/PD-L1 inhibitors is sacituzumab govitecan (Trodelvy, Gilead), which has already received FDA approval for metastatic triple-negative breast cancer, pretreated HR+/HER2- metastatic breast cancer, and metastatic urothelial cancer. Like datopotamab, sacituzumab targets TROP-2. Researchers reported preliminary results from the phase 2 EVOKE-02 study, in which the ADC was combined with pembrolizumab for the first-line treatment of metastatic NSCLC. The overall response rate was 56% (95% CI, 42%-69%). Among patients with PD-L1 tumor proportion score (TPS) ≥ 50%, the ORR was 69% (95% CI, 49%-85%) and 44% (95% CI, 26%-62%) among those with TPS < 50%. The disease control rate was 86% (95% CI, 68%-96%) and 78% (95% CI, 60%-91%), respectively. The most frequent treatment-emergent adverse events (TEAEs) were diarrhea, anemia, and asthenia, and 18% of patients discontinued the study drug because of TEAEs. (Abstract)

Ifinatamab deruxtecan

Ifinatamab deruxtecan (Daiichi Sankyo) targets the B7-H3 antigen, which is an immunoregulatory protein that is overexpressed in many tumors. In the DS7300-A-J101 study, it was tested in patients with advanced or metastatic solid tumors, without selection for B7-H3 expression. A subgroup analysis of 22 patients with small cell lung cancer (SCLC) showed an ORR of 52.4 (95% CI, 29.8-74.3), a complete response of 4.8%, and a partial response in 47.6%. The median PFS was 5.6 months (95% CI, 3.9-8.1) and median OS was 12.2 months (95% CI, 6.4-not applicable). The most common treatment-emergent adverse events were nausea (59.1%), fatigue (50.0%), anemia (27.3%), vomiting (27.3%), and decreased appetite (22.7%). (Abstract)

Antibody-drug conjugates (ADC) link a tumor-targeted antibody to a cytotoxic drug through a chemical linker and hold the promise of high potency. This has led to a burgeoning interest in solid tumors, with over 100 clinical trials in progress. Non–small cell lung cancer (NSCLC) is no exception. In 2022, the Food and Drug Administration approved trastuzumab DXd for pretreated NSCLC patients with HER2-mutant tumors. Two others have lung cancer breakthrough therapy designations from the FDA, including patritumab deruxtecan (HER3-DXd) for EGFR-mutant NSCLC and telisotuzumab vedotin for NSCLC that overexpresses c-Met.

At the annual World Conference on Lung Cancer, researchers outlined some of the latest developments in ADCs targeting the antigens HER3, trophoblast cell-surface antigen 2 (TROP-2), and the B7-H3 immunoregulatory protein, as single agents or in combination with immunotherapy. Following the presentations, discussant Helena Linardou, MD, PhD, emphasized the need for pharmacogenomics to predict toxicity and studies to understand resistance mechanisms. “ADCs are a new, rapidly evolving class of therapeutics, and I think that we will all have to be prepared for the future that is coming,” said Dr. Linardou, who is director of the 4th oncology department and the Comprehensive Clinical Trials Center at Metropolitan Hospital in Athens.

Researchers presented four ADC clinical trial updates.
 

Patritumab deruxtecan

Patritumab deruxtecan (Daiichi Sankyo) links a HER3 antibody to the topoisomerase I inhibitor deruxtecan (HER3-DXd). In the open-label, phase 2 HERTHENA-Lung01 trial, it was tested in patients with NSCLC EGFR-activation mutations, which occurs in 14%-38% of NSCLC cases. There are few options for these patients following failure of EGFR tyrosine kinase inhibitor therapy.

The study included 225 patients previously treated with EGFR tyrosine kinase inhibitors and platinum-based chemotherapy who received 5.6 mg/kg of HER3-DXd every 3 weeks. Over a median follow-up of 13.1 months and a median treatment duration of 5.5 months), 29.8% had a confirmed overall response (95% confidence interval, 23.9%-36.2%) with a median duration of 6.4 months (95% CI, 4.9-7.8). The median progression-free survival was 5.5 months (95% CI, 5.1-5.9), and the median OS was 11.9 months (95% CI, 11.2-13.1). The researchers noted similar outcomes among patients with different mechanisms of EGFR TKI resistance. The frequency of adverse events was similar to previous studies, with drug-related adverse events linked to treatment discontinuation of 7.1% interstitial lung disease in 5.3%. Among 30 patients with brain metastases, the confirmed intracranial response rate was 33.3% (95% CI, 17.3%-52.8%).

The study was published simultaneously online in the Journal of Clinical Oncology. (Abstract)
 

Datopotamab deruxtecan

PD-1/PD-L1 inhibitors are the first-line therapy for metastatic NSCLC, but there are efforts to improve outcomes through combination therapy. Datopotamab deruxtecan (Dato-DXd, Daiichi Sankyo, AstraZeneca) is an ADC targeting TROP2, and it has been shown in preclinical studies to enhance tumor responses to PD-1/PD-L1 inhibitors. The ADC improved progression-free survival (PFS), compared with docetaxel, in previously treated advanced or metastatic NSCLC.

In an interim analysis of the phase 1b TROPION-Lung04 study, researchers reported results from the combination of Dato-DXd with durvalumab with or without carboplatin. The study included 38 patients, some of whom had previously undergone treatment with immune checkpoint inhibitors. Nineteen patients received the doublet, and 14 received the carboplatin triplet. Grade 3 or higher treatment-emergent adverse events occurred in 42.1% of the doublet group and 71.4% of the triplet group. Interstitial lung disease occurred in 15.8% and 7.1% of the two groups, respectively. The objective response rate was 50.0% in the doublet group and 76.9% in the triplet group. The disease control rate was 92.9% and 92.3%, respectively. Durable responses occurred in both the first-line setting and the overall population. (Abstract)
 

Sacituzumab govitecan

Another ADC being tested with PD-1/PD-L1 inhibitors is sacituzumab govitecan (Trodelvy, Gilead), which has already received FDA approval for metastatic triple-negative breast cancer, pretreated HR+/HER2- metastatic breast cancer, and metastatic urothelial cancer. Like datopotamab, sacituzumab targets TROP-2. Researchers reported preliminary results from the phase 2 EVOKE-02 study, in which the ADC was combined with pembrolizumab for the first-line treatment of metastatic NSCLC. The overall response rate was 56% (95% CI, 42%-69%). Among patients with PD-L1 tumor proportion score (TPS) ≥ 50%, the ORR was 69% (95% CI, 49%-85%) and 44% (95% CI, 26%-62%) among those with TPS < 50%. The disease control rate was 86% (95% CI, 68%-96%) and 78% (95% CI, 60%-91%), respectively. The most frequent treatment-emergent adverse events (TEAEs) were diarrhea, anemia, and asthenia, and 18% of patients discontinued the study drug because of TEAEs. (Abstract)

Ifinatamab deruxtecan

Ifinatamab deruxtecan (Daiichi Sankyo) targets the B7-H3 antigen, which is an immunoregulatory protein that is overexpressed in many tumors. In the DS7300-A-J101 study, it was tested in patients with advanced or metastatic solid tumors, without selection for B7-H3 expression. A subgroup analysis of 22 patients with small cell lung cancer (SCLC) showed an ORR of 52.4 (95% CI, 29.8-74.3), a complete response of 4.8%, and a partial response in 47.6%. The median PFS was 5.6 months (95% CI, 3.9-8.1) and median OS was 12.2 months (95% CI, 6.4-not applicable). The most common treatment-emergent adverse events were nausea (59.1%), fatigue (50.0%), anemia (27.3%), vomiting (27.3%), and decreased appetite (22.7%). (Abstract)

SINGAPORE – Heavily pretreated patients with EGFR-mutated non–small cell lung cancer (NSCLC) may experience a clinically meaningful benefit with the antibody-drug conjugate (ADC) patritumab deruxtecan (HER3-DXd), new phase 2 trial results suggest.

In the trial, almost 30% of patients receiving HER3-DXd achieved an objective response, and patients’ median overall survival approached 1 year.

HER3-DXd has “emerged as a promising therapy” in this patient population, “for whom available treatment options provide only limited efficacy,” concluded lead study author Helena A. Yu, MD, from Memorial Sloan Kettering Cancer Center, New York City, who presented findings from the HERTHENA-Lung01 trial at the 2023 World Conference on Lung Cancer.

The results were simultaneously published in the Journal of Clinical Oncology.

Acquired resistance to therapy among heavily pretreated patients with EGFR-mutated NSCLC is “universal,” Dr. Yu explained. The mechanisms of resistance to first-line osimertinib are also “diverse” and hard to identify. Salvage therapies after failed EGFR tyrosine kinase inhibitor (TKI) therapy and platinum-based chemotherapy offer “only a limited and transient and clinical benefit,” she said.

And with limited treatment options available to patients resistant to TKIs, there is a “high unmet medical need” for new therapies, said Helena Linardou, MD, PhD, who was not involved in the study.

HER3-DXd consists of a fully human anti-HER3 immunoglobulin G1 monoclonal antibody (patritumab) attached to a topoisomerase I inhibitor payload (DXd) via a tetrapeptide-based cleavable linker.

HER3, Dr. Linardou explained, is a “biologically and clinically important target” in NSCLC. It is highly expressed in NSCLC, upregulated in TKI-resistant EGFR-mutated NSCLC, and is associated with a poor prognosis.

After promising phase 1 data, Dr. Yu and colleagues conducted a phase 2 trial in patients with advanced EGFR-mutated NSCLC who had progressed on systematic therapy and had received EGFR TKI and platinum-based chemotherapy. Patients could have active or previously treated asymptomatic brain metastases.

Patients were initially randomized either to a fixed-dose arm of HER3-DXd 5.6 mg/kg once every 3 weeks or an uptitration arm with doses escalating from 3.2 mg/kg to 4.8 mg/kg to 6.4 mg/kg over three cycles. However, Dr. Yu noted, enrollment in the uptitration arm closed early based on a “benefit-risk assessment.”

The current findings focus on the 225 patients in the fixed-dose arm.

About half of patients had a history of central nervous system metastasis, and patients had a median of three prior lines of systemic therapy. Most patients (92.9%) had previously received a third-generation EGFR TKI, about 40% had received immunotherapy, and all had received platinum-based chemotherapy.

After a median follow-up of 18.9 months, the confirmed objective response rate with HER3-DXd across the whole patient population was 29.8%. The median duration of response was 6.4 months, median progression-free survival was 5.5 months, and median overall survival was 11.9 months.

The results were virtually identical when looking only at patients who had received a third-generation EGFR TKI versus any EGFR TKI. Response rates were also similar regardless of the driver of EGFR TKI resistance.

Among the 30 patients with measurable brain metastases at baseline, 33.3% had a confirmed objective response to therapy. In this group, the disease control rate was 76.7% and the intracranial duration of response was 8.4 months.

To identify biomarkers of response to HER3-DXd, the team stratified the patients by baseline tumor HER3 membrane H-scores. Dr. Yu and colleagues found no differences in the likelihood of having a complete or partial response, stable disease, or progressive disease based on HER3 expression at study entry.

Looking at the safety of the ADC, only 7.1% of patients experienced a treatment-emergent adverse event associated with treatment discontinuation, but close to half of patients (45.3%) experienced a grade 3 or higher treatment-emergent adverse event. Interstitial lung disease, for instance, occurred in 5.3% of patients, including one patient who died.

The safety profile of HER3-DXd in this population appeared to be consistent with previous reports, Dr. Yu noted.

Overall, the findings suggest that “HER3-DXd provided clinically meaningful and durable efficacy” in patients with advanced EGFR-mutant NSCLC that has progressed after EGFR TKI and platinum-based chemotherapy, Dr. Yu said.

“Efficacy was observed across diverse mechanisms of resistance and across a broad range of pretreatment tumor HER3 expression” and the ADC demonstrated “clinically meaningful intracranial antitumor activity,” she added.

Dr. Linardou agreed that the current results suggest that HER3-DXd was associated with a “meaningful and durable efficacy,” including in patients with intracranial metastases, and she pointed to its “easy dosing schedule” and activity across patient subgroups.

However, she noted that, despite the researchers’ best efforts with the data available, “we don’t have a biomarker of activity,” which is a “general issue with ADCs.”

Still, Dr. Linardou said, “HER3 is now a clinically actionable therapeutic target, and this is a great bonus.”

The study was sponsored by Daiichi Sankyo. Dr. Yu declared relationships with AstraZeneca, Daiichi Sankyo, Blueprint Medicines, Janssen, C4 Therapeutics, Cullinan Oncology, Black Diamond Therapeutics, Taiho Oncology, and others. Other authors declare numerous relationships.

A version of this article first appeared on Medscape.com.

SINGAPORE – Heavily pretreated patients with EGFR-mutated non–small cell lung cancer (NSCLC) may experience a clinically meaningful benefit with the antibody-drug conjugate (ADC) patritumab deruxtecan (HER3-DXd), new phase 2 trial results suggest.

In the trial, almost 30% of patients receiving HER3-DXd achieved an objective response, and patients’ median overall survival approached 1 year.

HER3-DXd has “emerged as a promising therapy” in this patient population, “for whom available treatment options provide only limited efficacy,” concluded lead study author Helena A. Yu, MD, from Memorial Sloan Kettering Cancer Center, New York City, who presented findings from the HERTHENA-Lung01 trial at the 2023 World Conference on Lung Cancer.

The results were simultaneously published in the Journal of Clinical Oncology.

Acquired resistance to therapy among heavily pretreated patients with EGFR-mutated NSCLC is “universal,” Dr. Yu explained. The mechanisms of resistance to first-line osimertinib are also “diverse” and hard to identify. Salvage therapies after failed EGFR tyrosine kinase inhibitor (TKI) therapy and platinum-based chemotherapy offer “only a limited and transient and clinical benefit,” she said.

And with limited treatment options available to patients resistant to TKIs, there is a “high unmet medical need” for new therapies, said Helena Linardou, MD, PhD, who was not involved in the study.

HER3-DXd consists of a fully human anti-HER3 immunoglobulin G1 monoclonal antibody (patritumab) attached to a topoisomerase I inhibitor payload (DXd) via a tetrapeptide-based cleavable linker.

HER3, Dr. Linardou explained, is a “biologically and clinically important target” in NSCLC. It is highly expressed in NSCLC, upregulated in TKI-resistant EGFR-mutated NSCLC, and is associated with a poor prognosis.

After promising phase 1 data, Dr. Yu and colleagues conducted a phase 2 trial in patients with advanced EGFR-mutated NSCLC who had progressed on systematic therapy and had received EGFR TKI and platinum-based chemotherapy. Patients could have active or previously treated asymptomatic brain metastases.

Patients were initially randomized either to a fixed-dose arm of HER3-DXd 5.6 mg/kg once every 3 weeks or an uptitration arm with doses escalating from 3.2 mg/kg to 4.8 mg/kg to 6.4 mg/kg over three cycles. However, Dr. Yu noted, enrollment in the uptitration arm closed early based on a “benefit-risk assessment.”

The current findings focus on the 225 patients in the fixed-dose arm.

About half of patients had a history of central nervous system metastasis, and patients had a median of three prior lines of systemic therapy. Most patients (92.9%) had previously received a third-generation EGFR TKI, about 40% had received immunotherapy, and all had received platinum-based chemotherapy.

After a median follow-up of 18.9 months, the confirmed objective response rate with HER3-DXd across the whole patient population was 29.8%. The median duration of response was 6.4 months, median progression-free survival was 5.5 months, and median overall survival was 11.9 months.

The results were virtually identical when looking only at patients who had received a third-generation EGFR TKI versus any EGFR TKI. Response rates were also similar regardless of the driver of EGFR TKI resistance.

Among the 30 patients with measurable brain metastases at baseline, 33.3% had a confirmed objective response to therapy. In this group, the disease control rate was 76.7% and the intracranial duration of response was 8.4 months.

To identify biomarkers of response to HER3-DXd, the team stratified the patients by baseline tumor HER3 membrane H-scores. Dr. Yu and colleagues found no differences in the likelihood of having a complete or partial response, stable disease, or progressive disease based on HER3 expression at study entry.

Looking at the safety of the ADC, only 7.1% of patients experienced a treatment-emergent adverse event associated with treatment discontinuation, but close to half of patients (45.3%) experienced a grade 3 or higher treatment-emergent adverse event. Interstitial lung disease, for instance, occurred in 5.3% of patients, including one patient who died.

The safety profile of HER3-DXd in this population appeared to be consistent with previous reports, Dr. Yu noted.

Overall, the findings suggest that “HER3-DXd provided clinically meaningful and durable efficacy” in patients with advanced EGFR-mutant NSCLC that has progressed after EGFR TKI and platinum-based chemotherapy, Dr. Yu said.

“Efficacy was observed across diverse mechanisms of resistance and across a broad range of pretreatment tumor HER3 expression” and the ADC demonstrated “clinically meaningful intracranial antitumor activity,” she added.

Dr. Linardou agreed that the current results suggest that HER3-DXd was associated with a “meaningful and durable efficacy,” including in patients with intracranial metastases, and she pointed to its “easy dosing schedule” and activity across patient subgroups.

However, she noted that, despite the researchers’ best efforts with the data available, “we don’t have a biomarker of activity,” which is a “general issue with ADCs.”

Still, Dr. Linardou said, “HER3 is now a clinically actionable therapeutic target, and this is a great bonus.”

The study was sponsored by Daiichi Sankyo. Dr. Yu declared relationships with AstraZeneca, Daiichi Sankyo, Blueprint Medicines, Janssen, C4 Therapeutics, Cullinan Oncology, Black Diamond Therapeutics, Taiho Oncology, and others. Other authors declare numerous relationships.

A version of this article first appeared on Medscape.com.

SINGAPORE – Heavily pretreated patients with EGFR-mutated non–small cell lung cancer (NSCLC) may experience a clinically meaningful benefit with the antibody-drug conjugate (ADC) patritumab deruxtecan (HER3-DXd), new phase 2 trial results suggest.

In the trial, almost 30% of patients receiving HER3-DXd achieved an objective response, and patients’ median overall survival approached 1 year.

HER3-DXd has “emerged as a promising therapy” in this patient population, “for whom available treatment options provide only limited efficacy,” concluded lead study author Helena A. Yu, MD, from Memorial Sloan Kettering Cancer Center, New York City, who presented findings from the HERTHENA-Lung01 trial at the 2023 World Conference on Lung Cancer.

The results were simultaneously published in the Journal of Clinical Oncology.

Acquired resistance to therapy among heavily pretreated patients with EGFR-mutated NSCLC is “universal,” Dr. Yu explained. The mechanisms of resistance to first-line osimertinib are also “diverse” and hard to identify. Salvage therapies after failed EGFR tyrosine kinase inhibitor (TKI) therapy and platinum-based chemotherapy offer “only a limited and transient and clinical benefit,” she said.

And with limited treatment options available to patients resistant to TKIs, there is a “high unmet medical need” for new therapies, said Helena Linardou, MD, PhD, who was not involved in the study.

HER3-DXd consists of a fully human anti-HER3 immunoglobulin G1 monoclonal antibody (patritumab) attached to a topoisomerase I inhibitor payload (DXd) via a tetrapeptide-based cleavable linker.

HER3, Dr. Linardou explained, is a “biologically and clinically important target” in NSCLC. It is highly expressed in NSCLC, upregulated in TKI-resistant EGFR-mutated NSCLC, and is associated with a poor prognosis.

After promising phase 1 data, Dr. Yu and colleagues conducted a phase 2 trial in patients with advanced EGFR-mutated NSCLC who had progressed on systematic therapy and had received EGFR TKI and platinum-based chemotherapy. Patients could have active or previously treated asymptomatic brain metastases.

Patients were initially randomized either to a fixed-dose arm of HER3-DXd 5.6 mg/kg once every 3 weeks or an uptitration arm with doses escalating from 3.2 mg/kg to 4.8 mg/kg to 6.4 mg/kg over three cycles. However, Dr. Yu noted, enrollment in the uptitration arm closed early based on a “benefit-risk assessment.”

The current findings focus on the 225 patients in the fixed-dose arm.

About half of patients had a history of central nervous system metastasis, and patients had a median of three prior lines of systemic therapy. Most patients (92.9%) had previously received a third-generation EGFR TKI, about 40% had received immunotherapy, and all had received platinum-based chemotherapy.

After a median follow-up of 18.9 months, the confirmed objective response rate with HER3-DXd across the whole patient population was 29.8%. The median duration of response was 6.4 months, median progression-free survival was 5.5 months, and median overall survival was 11.9 months.

The results were virtually identical when looking only at patients who had received a third-generation EGFR TKI versus any EGFR TKI. Response rates were also similar regardless of the driver of EGFR TKI resistance.

Among the 30 patients with measurable brain metastases at baseline, 33.3% had a confirmed objective response to therapy. In this group, the disease control rate was 76.7% and the intracranial duration of response was 8.4 months.

To identify biomarkers of response to HER3-DXd, the team stratified the patients by baseline tumor HER3 membrane H-scores. Dr. Yu and colleagues found no differences in the likelihood of having a complete or partial response, stable disease, or progressive disease based on HER3 expression at study entry.

Looking at the safety of the ADC, only 7.1% of patients experienced a treatment-emergent adverse event associated with treatment discontinuation, but close to half of patients (45.3%) experienced a grade 3 or higher treatment-emergent adverse event. Interstitial lung disease, for instance, occurred in 5.3% of patients, including one patient who died.

The safety profile of HER3-DXd in this population appeared to be consistent with previous reports, Dr. Yu noted.

Overall, the findings suggest that “HER3-DXd provided clinically meaningful and durable efficacy” in patients with advanced EGFR-mutant NSCLC that has progressed after EGFR TKI and platinum-based chemotherapy, Dr. Yu said.

“Efficacy was observed across diverse mechanisms of resistance and across a broad range of pretreatment tumor HER3 expression” and the ADC demonstrated “clinically meaningful intracranial antitumor activity,” she added.

Dr. Linardou agreed that the current results suggest that HER3-DXd was associated with a “meaningful and durable efficacy,” including in patients with intracranial metastases, and she pointed to its “easy dosing schedule” and activity across patient subgroups.

However, she noted that, despite the researchers’ best efforts with the data available, “we don’t have a biomarker of activity,” which is a “general issue with ADCs.”

Still, Dr. Linardou said, “HER3 is now a clinically actionable therapeutic target, and this is a great bonus.”

The study was sponsored by Daiichi Sankyo. Dr. Yu declared relationships with AstraZeneca, Daiichi Sankyo, Blueprint Medicines, Janssen, C4 Therapeutics, Cullinan Oncology, Black Diamond Therapeutics, Taiho Oncology, and others. Other authors declare numerous relationships.

A version of this article first appeared on Medscape.com.

BACKGROUND

Implementation of lung cancer screening (LCS) in high-risk individuals reduces the risk of dying from lung cancer. The mortality benefit of LCS, however, can only be fully actualized in patients who adhere to follow-up screening examinations. Question: Does a centralized program offer better adherence to lung cancer screening compared with a decentralized approach?

METHODS

A retrospective analysis of a large Veterans Affairs medical center LCS program was conducted to compare adherence to follow-up screening in veterans established through the consult-based (centralized) program with those screened by primary care providers (decentralized). In addition, imaging referral rates from the centralized program were longitudinally reviewed and compared. The cohort included patients completing an LCS imaging examination between 10/2020 and 1/2022. Annual adherence was assessed in patients with a baseline Lung CT Screening Reporting and Data System (Lung-RADS) score of 1 or 2 and was defined as returning for follow-up imaging within 15 months. Outcomes among patients undergoing screening using a centralized and decentralized approach were compared using a two-proportion z-test.

RESULTS

A total of 1,114 patients with a baseline Lung-RADS score of 1 or 2 were included. The amount of low-dose CT (LDCT) imaging ordered for LCS increased exponentially from 2021 to 2023; however, a higher percentage of LDCT examinations were ordered via the decentralized approach, with no significant change observed over time (76%, 71%, and 74% in 2021, 2022, and 2023, respectively). Overall adherence was 42%. Within the centralized program, adherence was 74% compared to 34% using a decentralized approach (p <0.001).

IMPLICATIONS

Adherence to annual screening among eligible veterans is greater within a centralized program. Future research aimed at identifying barriers and maximizing adherence to LCS is needed.

BACKGROUND

Implementation of lung cancer screening (LCS) in high-risk individuals reduces the risk of dying from lung cancer. The mortality benefit of LCS, however, can only be fully actualized in patients who adhere to follow-up screening examinations. Question: Does a centralized program offer better adherence to lung cancer screening compared with a decentralized approach?

METHODS

A retrospective analysis of a large Veterans Affairs medical center LCS program was conducted to compare adherence to follow-up screening in veterans established through the consult-based (centralized) program with those screened by primary care providers (decentralized). In addition, imaging referral rates from the centralized program were longitudinally reviewed and compared. The cohort included patients completing an LCS imaging examination between 10/2020 and 1/2022. Annual adherence was assessed in patients with a baseline Lung CT Screening Reporting and Data System (Lung-RADS) score of 1 or 2 and was defined as returning for follow-up imaging within 15 months. Outcomes among patients undergoing screening using a centralized and decentralized approach were compared using a two-proportion z-test.

RESULTS

A total of 1,114 patients with a baseline Lung-RADS score of 1 or 2 were included. The amount of low-dose CT (LDCT) imaging ordered for LCS increased exponentially from 2021 to 2023; however, a higher percentage of LDCT examinations were ordered via the decentralized approach, with no significant change observed over time (76%, 71%, and 74% in 2021, 2022, and 2023, respectively). Overall adherence was 42%. Within the centralized program, adherence was 74% compared to 34% using a decentralized approach (p <0.001).

IMPLICATIONS

Adherence to annual screening among eligible veterans is greater within a centralized program. Future research aimed at identifying barriers and maximizing adherence to LCS is needed.

BACKGROUND

Implementation of lung cancer screening (LCS) in high-risk individuals reduces the risk of dying from lung cancer. The mortality benefit of LCS, however, can only be fully actualized in patients who adhere to follow-up screening examinations. Question: Does a centralized program offer better adherence to lung cancer screening compared with a decentralized approach?

METHODS

A retrospective analysis of a large Veterans Affairs medical center LCS program was conducted to compare adherence to follow-up screening in veterans established through the consult-based (centralized) program with those screened by primary care providers (decentralized). In addition, imaging referral rates from the centralized program were longitudinally reviewed and compared. The cohort included patients completing an LCS imaging examination between 10/2020 and 1/2022. Annual adherence was assessed in patients with a baseline Lung CT Screening Reporting and Data System (Lung-RADS) score of 1 or 2 and was defined as returning for follow-up imaging within 15 months. Outcomes among patients undergoing screening using a centralized and decentralized approach were compared using a two-proportion z-test.

RESULTS

A total of 1,114 patients with a baseline Lung-RADS score of 1 or 2 were included. The amount of low-dose CT (LDCT) imaging ordered for LCS increased exponentially from 2021 to 2023; however, a higher percentage of LDCT examinations were ordered via the decentralized approach, with no significant change observed over time (76%, 71%, and 74% in 2021, 2022, and 2023, respectively). Overall adherence was 42%. Within the centralized program, adherence was 74% compared to 34% using a decentralized approach (p <0.001).

IMPLICATIONS

Adherence to annual screening among eligible veterans is greater within a centralized program. Future research aimed at identifying barriers and maximizing adherence to LCS is needed.

BACKGROUND

Tobacco use is a known factor in oncologic outcomes in Veterans. Lung cancer is not only the leading cause of cancer death in the U.S., but it is also more prevalent among Veterans. Tobacco use is underassessed and undertreated in healthcare settings. Newly diagnosed cancer patients seen at the Day-Treatment Center of Edward Hines Jr. VA Hospital were not consistently screened for tobacco use or appropriately referred to the hospital-based Tobacco Cessation Program.

PURPOSE

This quality improvement project was created to use existing resources to increase the percentage of newly diagnosed cancer patients screened for tobacco use based off the CoC Just ASK Quality Improvement Project and Clinical Study.

METHODS/DATA ANALYSIS

Using Plan-Do-Study- Act (PDSA) quality improvement methodology, a multidisciplinary team led by Oncology Nursing, Oncologists, Pharmacy, Social Work and Behavioral Health, to standardize processes to increase the percentage of tobacco use screening. The primary intervention was designating nurse educators to standardize the cancer treatment education process to include an assessment for tobacco by using the Just ASK criteria. The primary study goal was to increase tobacco use screening from 54.8% (Baseline Data) to 85% (Target State Goal).

RESULTS

Baseline number of tobacco screening in 2021 was 54.8%. From 1/1/22-6/30/22, 52.8% were screened using the Just ASK criteria. After the first PDSA cycle, from 7/1/22-12/31/22, tobacco screenings increased to 95.1%. PDSA cycle two revealed a 25% increase in Q1 accepting referrals. 62.5% of positive tobacco users agreed to accept care compared to 25% in PDSA cycle one.

CONCLUSIONS/IMPLICATIONS

The quality study met the primary goal of screening newly diagnosed cancer patients. The success of this project supported the use of existing VA hospital-based program resources such as educational materials, supportive medication, and behavioral counseling. Interventions directed at standardization of clinical workflow processes through nursing education and linkage to resources increased tobacco screening among newly diagnosed Veterans with cancer. Planned PDSA cycle two will spread standardized processes in the Rad/Onc Department and build capacity to offer smoking cessation assistance to newly diagnosed cancer patients who report as a current smoker. Annual VHA clinical reminders will be built in and satisfied by using an EMR tobacco screen template.

BACKGROUND

Tobacco use is a known factor in oncologic outcomes in Veterans. Lung cancer is not only the leading cause of cancer death in the U.S., but it is also more prevalent among Veterans. Tobacco use is underassessed and undertreated in healthcare settings. Newly diagnosed cancer patients seen at the Day-Treatment Center of Edward Hines Jr. VA Hospital were not consistently screened for tobacco use or appropriately referred to the hospital-based Tobacco Cessation Program.

PURPOSE

This quality improvement project was created to use existing resources to increase the percentage of newly diagnosed cancer patients screened for tobacco use based off the CoC Just ASK Quality Improvement Project and Clinical Study.

METHODS/DATA ANALYSIS

Using Plan-Do-Study- Act (PDSA) quality improvement methodology, a multidisciplinary team led by Oncology Nursing, Oncologists, Pharmacy, Social Work and Behavioral Health, to standardize processes to increase the percentage of tobacco use screening. The primary intervention was designating nurse educators to standardize the cancer treatment education process to include an assessment for tobacco by using the Just ASK criteria. The primary study goal was to increase tobacco use screening from 54.8% (Baseline Data) to 85% (Target State Goal).

RESULTS

Baseline number of tobacco screening in 2021 was 54.8%. From 1/1/22-6/30/22, 52.8% were screened using the Just ASK criteria. After the first PDSA cycle, from 7/1/22-12/31/22, tobacco screenings increased to 95.1%. PDSA cycle two revealed a 25% increase in Q1 accepting referrals. 62.5% of positive tobacco users agreed to accept care compared to 25% in PDSA cycle one.

CONCLUSIONS/IMPLICATIONS

The quality study met the primary goal of screening newly diagnosed cancer patients. The success of this project supported the use of existing VA hospital-based program resources such as educational materials, supportive medication, and behavioral counseling. Interventions directed at standardization of clinical workflow processes through nursing education and linkage to resources increased tobacco screening among newly diagnosed Veterans with cancer. Planned PDSA cycle two will spread standardized processes in the Rad/Onc Department and build capacity to offer smoking cessation assistance to newly diagnosed cancer patients who report as a current smoker. Annual VHA clinical reminders will be built in and satisfied by using an EMR tobacco screen template.

BACKGROUND

Tobacco use is a known factor in oncologic outcomes in Veterans. Lung cancer is not only the leading cause of cancer death in the U.S., but it is also more prevalent among Veterans. Tobacco use is underassessed and undertreated in healthcare settings. Newly diagnosed cancer patients seen at the Day-Treatment Center of Edward Hines Jr. VA Hospital were not consistently screened for tobacco use or appropriately referred to the hospital-based Tobacco Cessation Program.

PURPOSE

This quality improvement project was created to use existing resources to increase the percentage of newly diagnosed cancer patients screened for tobacco use based off the CoC Just ASK Quality Improvement Project and Clinical Study.

METHODS/DATA ANALYSIS

Using Plan-Do-Study- Act (PDSA) quality improvement methodology, a multidisciplinary team led by Oncology Nursing, Oncologists, Pharmacy, Social Work and Behavioral Health, to standardize processes to increase the percentage of tobacco use screening. The primary intervention was designating nurse educators to standardize the cancer treatment education process to include an assessment for tobacco by using the Just ASK criteria. The primary study goal was to increase tobacco use screening from 54.8% (Baseline Data) to 85% (Target State Goal).

RESULTS

Baseline number of tobacco screening in 2021 was 54.8%. From 1/1/22-6/30/22, 52.8% were screened using the Just ASK criteria. After the first PDSA cycle, from 7/1/22-12/31/22, tobacco screenings increased to 95.1%. PDSA cycle two revealed a 25% increase in Q1 accepting referrals. 62.5% of positive tobacco users agreed to accept care compared to 25% in PDSA cycle one.

CONCLUSIONS/IMPLICATIONS

The quality study met the primary goal of screening newly diagnosed cancer patients. The success of this project supported the use of existing VA hospital-based program resources such as educational materials, supportive medication, and behavioral counseling. Interventions directed at standardization of clinical workflow processes through nursing education and linkage to resources increased tobacco screening among newly diagnosed Veterans with cancer. Planned PDSA cycle two will spread standardized processes in the Rad/Onc Department and build capacity to offer smoking cessation assistance to newly diagnosed cancer patients who report as a current smoker. Annual VHA clinical reminders will be built in and satisfied by using an EMR tobacco screen template.

PURPOSE

Assess the clinical impact (CI) of UV-related DNA damage signatures (UVsig) in Veterans with cancer of unknown primary (CUP) and cancer of extracutaneous origin (CEO).

BACKGROUND

UVsig have been reported in CUP and CEO (i.e. head and neck cancer and lung cancer). The presence of UVsig suggests a cutaneous origin and potential misclassification of CEO using conventional histopathologic evaluation. Literature on the association of UVsig in pan-cancer genomics is limited.

METHODS

This is a retrospective study of Veterans who underwent comprehensive genomic profiling with FoundationOne CDx during 2/1/2019 to 9/30/2022 through the VA National Precision Oncology Program. The outcome was the CI of UVsig (high, medium, and low) determined by blinded chart reviews: (1) high: UVsig leading to change in diagnoses (CID) and a different first-line therapy (FLT) would have been offered; (2) medium: UVsig leading to CID, but appropriate FLT offered; (3) low: diagnoses modified by clinicians and treated as cutaneous cancers. NCCN Guidelines were referenced for FLT.

DATA ANALYSIS

Descriptive statistics and chi-square tests were utilized to evaluate the UVsig CI.

RESULTS

Among 5,565 cases with 10 or more assessable alterations for UVsig analysis, 650 (11.7%) were positive for UVsig. CUP and CEO cohorts each had 41 cases analyzed. In the CUP cases, 20 (48.8%), 9 (21.9%), and 12 (29.3%) were categorized as having high, medium, and low CI, respectively; and in the CEO cases, it was 22 (53.7%), 15 (36.6%), and 4 (9.8%). There was no difference statistically between the CUP and CEO groups on the percentage distribution of CI (p=0.06). Among the 42 out of 82 cases having high CI, 37 (88.1%) received cytotoxic chemotherapy without any indication, and 5 (11.9%) were not offered immunotherapy (IO) as FLT. More than half of the 82 cases had high CI; more than 90% of the CEO cases had high and medium CI.

IMPLICATIONS

UVsig serves as a useful biomarker for cancers with cutaneous origin. About 1% of the 5,565 cases analyzed had high UVsig CI. Knowledge of UVsig could lead to omission of chemotherapy (hence avoiding toxicities) or addition of IO (for potential benefits).

PURPOSE

Assess the clinical impact (CI) of UV-related DNA damage signatures (UVsig) in Veterans with cancer of unknown primary (CUP) and cancer of extracutaneous origin (CEO).

BACKGROUND

UVsig have been reported in CUP and CEO (i.e. head and neck cancer and lung cancer). The presence of UVsig suggests a cutaneous origin and potential misclassification of CEO using conventional histopathologic evaluation. Literature on the association of UVsig in pan-cancer genomics is limited.

METHODS

This is a retrospective study of Veterans who underwent comprehensive genomic profiling with FoundationOne CDx during 2/1/2019 to 9/30/2022 through the VA National Precision Oncology Program. The outcome was the CI of UVsig (high, medium, and low) determined by blinded chart reviews: (1) high: UVsig leading to change in diagnoses (CID) and a different first-line therapy (FLT) would have been offered; (2) medium: UVsig leading to CID, but appropriate FLT offered; (3) low: diagnoses modified by clinicians and treated as cutaneous cancers. NCCN Guidelines were referenced for FLT.

DATA ANALYSIS

Descriptive statistics and chi-square tests were utilized to evaluate the UVsig CI.

RESULTS

Among 5,565 cases with 10 or more assessable alterations for UVsig analysis, 650 (11.7%) were positive for UVsig. CUP and CEO cohorts each had 41 cases analyzed. In the CUP cases, 20 (48.8%), 9 (21.9%), and 12 (29.3%) were categorized as having high, medium, and low CI, respectively; and in the CEO cases, it was 22 (53.7%), 15 (36.6%), and 4 (9.8%). There was no difference statistically between the CUP and CEO groups on the percentage distribution of CI (p=0.06). Among the 42 out of 82 cases having high CI, 37 (88.1%) received cytotoxic chemotherapy without any indication, and 5 (11.9%) were not offered immunotherapy (IO) as FLT. More than half of the 82 cases had high CI; more than 90% of the CEO cases had high and medium CI.

IMPLICATIONS

UVsig serves as a useful biomarker for cancers with cutaneous origin. About 1% of the 5,565 cases analyzed had high UVsig CI. Knowledge of UVsig could lead to omission of chemotherapy (hence avoiding toxicities) or addition of IO (for potential benefits).

PURPOSE

Assess the clinical impact (CI) of UV-related DNA damage signatures (UVsig) in Veterans with cancer of unknown primary (CUP) and cancer of extracutaneous origin (CEO).

BACKGROUND

UVsig have been reported in CUP and CEO (i.e. head and neck cancer and lung cancer). The presence of UVsig suggests a cutaneous origin and potential misclassification of CEO using conventional histopathologic evaluation. Literature on the association of UVsig in pan-cancer genomics is limited.

METHODS

This is a retrospective study of Veterans who underwent comprehensive genomic profiling with FoundationOne CDx during 2/1/2019 to 9/30/2022 through the VA National Precision Oncology Program. The outcome was the CI of UVsig (high, medium, and low) determined by blinded chart reviews: (1) high: UVsig leading to change in diagnoses (CID) and a different first-line therapy (FLT) would have been offered; (2) medium: UVsig leading to CID, but appropriate FLT offered; (3) low: diagnoses modified by clinicians and treated as cutaneous cancers. NCCN Guidelines were referenced for FLT.

DATA ANALYSIS

Descriptive statistics and chi-square tests were utilized to evaluate the UVsig CI.

RESULTS

Among 5,565 cases with 10 or more assessable alterations for UVsig analysis, 650 (11.7%) were positive for UVsig. CUP and CEO cohorts each had 41 cases analyzed. In the CUP cases, 20 (48.8%), 9 (21.9%), and 12 (29.3%) were categorized as having high, medium, and low CI, respectively; and in the CEO cases, it was 22 (53.7%), 15 (36.6%), and 4 (9.8%). There was no difference statistically between the CUP and CEO groups on the percentage distribution of CI (p=0.06). Among the 42 out of 82 cases having high CI, 37 (88.1%) received cytotoxic chemotherapy without any indication, and 5 (11.9%) were not offered immunotherapy (IO) as FLT. More than half of the 82 cases had high CI; more than 90% of the CEO cases had high and medium CI.

IMPLICATIONS

UVsig serves as a useful biomarker for cancers with cutaneous origin. About 1% of the 5,565 cases analyzed had high UVsig CI. Knowledge of UVsig could lead to omission of chemotherapy (hence avoiding toxicities) or addition of IO (for potential benefits).

BACKGROUND

In 2017, the Thoracic Tumor Board realized that there were patients whose lung resections had critical review of the slides and reports prior to presentation. Errors were found which resulted in a change of the pathology Tumor Nodal Metastases (pTNM) staging for the patient. The impacts were important for determining appropriate therapy. It was decided to systematically review all lung cancer resections for accuracy before determining definitive therapy recommendations.

METHODS

All lung resections for malignancy were examined prior and up to 2 days of completion for accuracy of tumor type, tumor size, tumor grade, lymph node metastases and pathologic stage (pTNM). Any errors found were given to the original pathologist for a change in the report before release or for a modified report to be issued.

RESULTS

From June 2017 to December 2020, there were 91 lung resections with 28 (30.77%) errors. Errors included: 16 incorrect pathologic staging, 5 missed tumors in lung and lymph nodes, 2 unexamined stapled surgical margins, 1 wrong site, 1 incorrect lymph node number and 2 missed tumor vascular invasion.

IMPLICATIONS

Quality improvement (QI) review of lung resections by a second pathologist is important and may clearly improve pathologic staging for lung cancer patients. It can be added to QI programs currently used in Surgical Pathology. It is important in directing appropriate postsurgical therapies.

BACKGROUND

In 2017, the Thoracic Tumor Board realized that there were patients whose lung resections had critical review of the slides and reports prior to presentation. Errors were found which resulted in a change of the pathology Tumor Nodal Metastases (pTNM) staging for the patient. The impacts were important for determining appropriate therapy. It was decided to systematically review all lung cancer resections for accuracy before determining definitive therapy recommendations.

METHODS

All lung resections for malignancy were examined prior and up to 2 days of completion for accuracy of tumor type, tumor size, tumor grade, lymph node metastases and pathologic stage (pTNM). Any errors found were given to the original pathologist for a change in the report before release or for a modified report to be issued.

RESULTS

From June 2017 to December 2020, there were 91 lung resections with 28 (30.77%) errors. Errors included: 16 incorrect pathologic staging, 5 missed tumors in lung and lymph nodes, 2 unexamined stapled surgical margins, 1 wrong site, 1 incorrect lymph node number and 2 missed tumor vascular invasion.

IMPLICATIONS

Quality improvement (QI) review of lung resections by a second pathologist is important and may clearly improve pathologic staging for lung cancer patients. It can be added to QI programs currently used in Surgical Pathology. It is important in directing appropriate postsurgical therapies.

BACKGROUND

In 2017, the Thoracic Tumor Board realized that there were patients whose lung resections had critical review of the slides and reports prior to presentation. Errors were found which resulted in a change of the pathology Tumor Nodal Metastases (pTNM) staging for the patient. The impacts were important for determining appropriate therapy. It was decided to systematically review all lung cancer resections for accuracy before determining definitive therapy recommendations.

METHODS

All lung resections for malignancy were examined prior and up to 2 days of completion for accuracy of tumor type, tumor size, tumor grade, lymph node metastases and pathologic stage (pTNM). Any errors found were given to the original pathologist for a change in the report before release or for a modified report to be issued.

RESULTS

From June 2017 to December 2020, there were 91 lung resections with 28 (30.77%) errors. Errors included: 16 incorrect pathologic staging, 5 missed tumors in lung and lymph nodes, 2 unexamined stapled surgical margins, 1 wrong site, 1 incorrect lymph node number and 2 missed tumor vascular invasion.

IMPLICATIONS

Quality improvement (QI) review of lung resections by a second pathologist is important and may clearly improve pathologic staging for lung cancer patients. It can be added to QI programs currently used in Surgical Pathology. It is important in directing appropriate postsurgical therapies.

Smokers who followed an adaptive treatment regimen with drug patches had greater smoking abstinence after 12 weeks than did those who followed a standard regimen, based on data from 188 individuals.

Adaptive pharmacotherapy is a common strategy across many medical conditions, but its use in smoking cessation treatments involving skin patches has not been examined, wrote James M. Davis, MD, of Duke University, Durham, N.C., and colleagues.

In a study published in JAMA Network Open, the researchers reviewed data from 188 adults who sought smoking cessation treatment at a university health system between February 2018 and May 2020. The researchers planned to enroll 300 adults, but enrollment was truncated because of the COVID-19 pandemic.

Participants chose between varenicline or nicotine patches, and then were randomized to an adaptive or standard treatment regimen. All participants started their medication 4 weeks before their target quit smoking day.

A total of 127 participants chose varenicline, with 64 randomized to adaptive treatment and 63 randomized to standard treatment; 61 participants chose nicotine patches, with 31 randomized to adaptive treatment and 30 randomized to standard treatment. Overall, participants smoked a mean of 15.4 cigarettes per day at baseline. The mean age of the participants was 49.1 years; 54% were female, 52% were White, and 48% were Black. Baseline demographics were similar between the groups.

The primary outcome was 30-day continuous abstinence from smoking (biochemically verified) at 12 weeks after each participant’s target quit date.

After 2 weeks (2 weeks before the target quit smoking day), all participants were assessed for treatment response. Those in the adaptive group who were deemed responders, defined as a reduction in daily cigarettes of at least 50%, received placebo bupropion. Those in the adaptive group deemed nonresponders received 150 mg bupropion twice daily in addition to their patch regimen. The standard treatment group also received placebo bupropion.

At 12 weeks after the target quit day, 24% of the adaptive group demonstrated 30-day continuous smoking abstinence, compared with 9% of the standard group (odds ratio, 3.38; P = .004). Smoking abstinence was higher in the adaptive vs. placebo groups for those who used varenicline patches (28% vs. 8%; OR, 4.54) and for those who used nicotine patches (16% vs. 10%; OR, 1.73).

In addition, 7-day smoking abstinence measured at a 2-week postquit day visit was three times higher in the adaptive group compared with the standard treatment group (32% vs. 11%; OR, 3.30).

No incidents of death, life-threatening events, hospitalization, or persistent or significant disability or incapacity related to the study were reported; one death in the varenicline group was attributable to stage 4 cancer.

The findings were limited by several factors including the few or no participants of Alaska Native, American Indian, Hispanic, or Pacific Islander ethnicities, or those who were multiracial. The free medication and modest compensation for study visits further reduce generalizability, the researchers noted. Other limitations included the smaller-than-intended sample size and inability to assess individual components of adaptive treatment, they said.

However, the results support the value of adaptive treatment and suggest that adaptive treatment with precessation varenicline or nicotine patches followed by bupropion for nonresponders is more effective than standard treatment for smoking cessation.

The study was supported by the National Institute on Drug Abuse; the varenicline was provided by Pfizer. Dr. Davis had no financial conflicts to disclose.

Smokers who followed an adaptive treatment regimen with drug patches had greater smoking abstinence after 12 weeks than did those who followed a standard regimen, based on data from 188 individuals.

Adaptive pharmacotherapy is a common strategy across many medical conditions, but its use in smoking cessation treatments involving skin patches has not been examined, wrote James M. Davis, MD, of Duke University, Durham, N.C., and colleagues.

In a study published in JAMA Network Open, the researchers reviewed data from 188 adults who sought smoking cessation treatment at a university health system between February 2018 and May 2020. The researchers planned to enroll 300 adults, but enrollment was truncated because of the COVID-19 pandemic.

Participants chose between varenicline or nicotine patches, and then were randomized to an adaptive or standard treatment regimen. All participants started their medication 4 weeks before their target quit smoking day.

A total of 127 participants chose varenicline, with 64 randomized to adaptive treatment and 63 randomized to standard treatment; 61 participants chose nicotine patches, with 31 randomized to adaptive treatment and 30 randomized to standard treatment. Overall, participants smoked a mean of 15.4 cigarettes per day at baseline. The mean age of the participants was 49.1 years; 54% were female, 52% were White, and 48% were Black. Baseline demographics were similar between the groups.

The primary outcome was 30-day continuous abstinence from smoking (biochemically verified) at 12 weeks after each participant’s target quit date.

After 2 weeks (2 weeks before the target quit smoking day), all participants were assessed for treatment response. Those in the adaptive group who were deemed responders, defined as a reduction in daily cigarettes of at least 50%, received placebo bupropion. Those in the adaptive group deemed nonresponders received 150 mg bupropion twice daily in addition to their patch regimen. The standard treatment group also received placebo bupropion.

At 12 weeks after the target quit day, 24% of the adaptive group demonstrated 30-day continuous smoking abstinence, compared with 9% of the standard group (odds ratio, 3.38; P = .004). Smoking abstinence was higher in the adaptive vs. placebo groups for those who used varenicline patches (28% vs. 8%; OR, 4.54) and for those who used nicotine patches (16% vs. 10%; OR, 1.73).

In addition, 7-day smoking abstinence measured at a 2-week postquit day visit was three times higher in the adaptive group compared with the standard treatment group (32% vs. 11%; OR, 3.30).

No incidents of death, life-threatening events, hospitalization, or persistent or significant disability or incapacity related to the study were reported; one death in the varenicline group was attributable to stage 4 cancer.

The findings were limited by several factors including the few or no participants of Alaska Native, American Indian, Hispanic, or Pacific Islander ethnicities, or those who were multiracial. The free medication and modest compensation for study visits further reduce generalizability, the researchers noted. Other limitations included the smaller-than-intended sample size and inability to assess individual components of adaptive treatment, they said.

However, the results support the value of adaptive treatment and suggest that adaptive treatment with precessation varenicline or nicotine patches followed by bupropion for nonresponders is more effective than standard treatment for smoking cessation.

The study was supported by the National Institute on Drug Abuse; the varenicline was provided by Pfizer. Dr. Davis had no financial conflicts to disclose.

Smokers who followed an adaptive treatment regimen with drug patches had greater smoking abstinence after 12 weeks than did those who followed a standard regimen, based on data from 188 individuals.

Adaptive pharmacotherapy is a common strategy across many medical conditions, but its use in smoking cessation treatments involving skin patches has not been examined, wrote James M. Davis, MD, of Duke University, Durham, N.C., and colleagues.

In a study published in JAMA Network Open, the researchers reviewed data from 188 adults who sought smoking cessation treatment at a university health system between February 2018 and May 2020. The researchers planned to enroll 300 adults, but enrollment was truncated because of the COVID-19 pandemic.

Participants chose between varenicline or nicotine patches, and then were randomized to an adaptive or standard treatment regimen. All participants started their medication 4 weeks before their target quit smoking day.

A total of 127 participants chose varenicline, with 64 randomized to adaptive treatment and 63 randomized to standard treatment; 61 participants chose nicotine patches, with 31 randomized to adaptive treatment and 30 randomized to standard treatment. Overall, participants smoked a mean of 15.4 cigarettes per day at baseline. The mean age of the participants was 49.1 years; 54% were female, 52% were White, and 48% were Black. Baseline demographics were similar between the groups.

The primary outcome was 30-day continuous abstinence from smoking (biochemically verified) at 12 weeks after each participant’s target quit date.

After 2 weeks (2 weeks before the target quit smoking day), all participants were assessed for treatment response. Those in the adaptive group who were deemed responders, defined as a reduction in daily cigarettes of at least 50%, received placebo bupropion. Those in the adaptive group deemed nonresponders received 150 mg bupropion twice daily in addition to their patch regimen. The standard treatment group also received placebo bupropion.

At 12 weeks after the target quit day, 24% of the adaptive group demonstrated 30-day continuous smoking abstinence, compared with 9% of the standard group (odds ratio, 3.38; P = .004). Smoking abstinence was higher in the adaptive vs. placebo groups for those who used varenicline patches (28% vs. 8%; OR, 4.54) and for those who used nicotine patches (16% vs. 10%; OR, 1.73).

In addition, 7-day smoking abstinence measured at a 2-week postquit day visit was three times higher in the adaptive group compared with the standard treatment group (32% vs. 11%; OR, 3.30).

No incidents of death, life-threatening events, hospitalization, or persistent or significant disability or incapacity related to the study were reported; one death in the varenicline group was attributable to stage 4 cancer.

The findings were limited by several factors including the few or no participants of Alaska Native, American Indian, Hispanic, or Pacific Islander ethnicities, or those who were multiracial. The free medication and modest compensation for study visits further reduce generalizability, the researchers noted. Other limitations included the smaller-than-intended sample size and inability to assess individual components of adaptive treatment, they said.

However, the results support the value of adaptive treatment and suggest that adaptive treatment with precessation varenicline or nicotine patches followed by bupropion for nonresponders is more effective than standard treatment for smoking cessation.

The study was supported by the National Institute on Drug Abuse; the varenicline was provided by Pfizer. Dr. Davis had no financial conflicts to disclose.

Adults with asthma who were newly prescribed mepolizumab showed significant improvement in symptoms after 1 year regardless of comorbidities, based on data from 822 individuals.

Comorbidities including chronic rhinosinusitis with polyps (CRSwNP), gastroesophageal reflux disease GERD), anxiety and depression, and chronic obstructive pulmonary disorder (COPD) are common in patients with severe asthma and add to the disease burden, wrote Mark C. Liu, MD, of Johns Hopkins University, Baltimore, and colleagues.

“Some comorbidities, such as CRSwNP, share pathophysiological mechanisms with severe asthma, with interleukin-5 (IL-5),” and treatments targeting IL-5 could improve outcomes, they said.

In the real-world REALITI-A study, mepolizumab, a humanized monoclonal antibody that targets IL-5, significantly reduced asthma exacerbation and oral corticosteroid use in severe asthma patients, they said.

To assess the impact of mepolizumab on patients with comorbidities, the researchers conducted a post hoc analysis of 822 adults with severe asthma, including 321 with CRSwNP, 309 with GERD, 203 with depression/anxiety, and 81 with COPD. The findings were published in the Journal of Allergy and Clinical Immunology: In Practice.

The main outcomes were the rate of clinically significant asthma exacerbations (CSEs) between the 12 months before and after mepolizumab initiation, and the changes from baseline in the daily maintenance use of oral corticosteroids (OCS).

Across all comorbidities, the rate of CSEs decreased significantly from the pretreatment period to the follow-up period, from 4.28 events per year to 1.23 events per year.

“A numerically greater reduction in the rate of CSEs was reported for patients with versus without CRSwNP, whereas the reverse was reported for patients with versus without COPD and depression/anxiety, although the confidence intervals were large for the with COPD subgroup,” the researchers wrote.

The median maintenance dose of oral corticosteroids decreased by at least 50% across all comorbidities after mepolizumab treatment; patients with CRSwNP had the greatest reduction (83%).

In addition, scores on the Asthma Control Questionnaire–5 decreased by at least 0.63 points, and least squared (LS) mean changes in forced expiratory volume per second (FEV₁) increased from baseline across all comorbidities after mepolizumab treatment by at least 74 mL.

Although patients with versus without CRSwNP had greater improvements, patients without GERD, depression/anxiety, and COPD had greater improvements than did those without the respective conditions with the exception of greater FEV₁ improvement in patients with vs. without COPD.

“Patients with severe asthma and comorbid CRSwNP are recognized as having a high disease burden, as demonstrated by more frequent exacerbations,” the researchers wrote in their discussion. “Mepolizumab may serve to reduce the disease burden of this high-risk group by targeting the common pathophysiological pathway of IL-5 and eosinophilic-driven inflammation because it has proven clinical benefits in treating asthma and CRSwNP separately and together,” and the current study findings support the use of mepolizumab for this population in particular, they said.

The findings were limited by several factors including the incomplete data for voluntary assessments, the post hoc design and relatively small numbers of patients in various subgroups, notably COPD, and the potential inaccurate diagnosis of COPD, the researchers noted.

“Nevertheless, because the amount of improvement in each outcome following mepolizumab treatment differed depending on the comorbidity in question, our findings highlight the impact that comorbidities and their prevalence and severity have on outcomes,” and the overall success of mepolizumab across clinical characteristics and comorbidities supports the generalizability of the findings to the larger population of adults with severe asthma, they concluded.

The study was supported by GlaxoSmithKline. Dr. Liu disclosed research funding from GSK, Boehringer Ingelheim, and Gossamer Bio, and participation on advisory boards for AstraZeneca, GSK, and Gossamer Bio.

Adults with asthma who were newly prescribed mepolizumab showed significant improvement in symptoms after 1 year regardless of comorbidities, based on data from 822 individuals.

Comorbidities including chronic rhinosinusitis with polyps (CRSwNP), gastroesophageal reflux disease GERD), anxiety and depression, and chronic obstructive pulmonary disorder (COPD) are common in patients with severe asthma and add to the disease burden, wrote Mark C. Liu, MD, of Johns Hopkins University, Baltimore, and colleagues.

“Some comorbidities, such as CRSwNP, share pathophysiological mechanisms with severe asthma, with interleukin-5 (IL-5),” and treatments targeting IL-5 could improve outcomes, they said.

In the real-world REALITI-A study, mepolizumab, a humanized monoclonal antibody that targets IL-5, significantly reduced asthma exacerbation and oral corticosteroid use in severe asthma patients, they said.

To assess the impact of mepolizumab on patients with comorbidities, the researchers conducted a post hoc analysis of 822 adults with severe asthma, including 321 with CRSwNP, 309 with GERD, 203 with depression/anxiety, and 81 with COPD. The findings were published in the Journal of Allergy and Clinical Immunology: In Practice.

The main outcomes were the rate of clinically significant asthma exacerbations (CSEs) between the 12 months before and after mepolizumab initiation, and the changes from baseline in the daily maintenance use of oral corticosteroids (OCS).

Across all comorbidities, the rate of CSEs decreased significantly from the pretreatment period to the follow-up period, from 4.28 events per year to 1.23 events per year.

“A numerically greater reduction in the rate of CSEs was reported for patients with versus without CRSwNP, whereas the reverse was reported for patients with versus without COPD and depression/anxiety, although the confidence intervals were large for the with COPD subgroup,” the researchers wrote.

The median maintenance dose of oral corticosteroids decreased by at least 50% across all comorbidities after mepolizumab treatment; patients with CRSwNP had the greatest reduction (83%).

In addition, scores on the Asthma Control Questionnaire–5 decreased by at least 0.63 points, and least squared (LS) mean changes in forced expiratory volume per second (FEV₁) increased from baseline across all comorbidities after mepolizumab treatment by at least 74 mL.

Although patients with versus without CRSwNP had greater improvements, patients without GERD, depression/anxiety, and COPD had greater improvements than did those without the respective conditions with the exception of greater FEV₁ improvement in patients with vs. without COPD.

“Patients with severe asthma and comorbid CRSwNP are recognized as having a high disease burden, as demonstrated by more frequent exacerbations,” the researchers wrote in their discussion. “Mepolizumab may serve to reduce the disease burden of this high-risk group by targeting the common pathophysiological pathway of IL-5 and eosinophilic-driven inflammation because it has proven clinical benefits in treating asthma and CRSwNP separately and together,” and the current study findings support the use of mepolizumab for this population in particular, they said.

The findings were limited by several factors including the incomplete data for voluntary assessments, the post hoc design and relatively small numbers of patients in various subgroups, notably COPD, and the potential inaccurate diagnosis of COPD, the researchers noted.

“Nevertheless, because the amount of improvement in each outcome following mepolizumab treatment differed depending on the comorbidity in question, our findings highlight the impact that comorbidities and their prevalence and severity have on outcomes,” and the overall success of mepolizumab across clinical characteristics and comorbidities supports the generalizability of the findings to the larger population of adults with severe asthma, they concluded.

The study was supported by GlaxoSmithKline. Dr. Liu disclosed research funding from GSK, Boehringer Ingelheim, and Gossamer Bio, and participation on advisory boards for AstraZeneca, GSK, and Gossamer Bio.

Adults with asthma who were newly prescribed mepolizumab showed significant improvement in symptoms after 1 year regardless of comorbidities, based on data from 822 individuals.

Comorbidities including chronic rhinosinusitis with polyps (CRSwNP), gastroesophageal reflux disease GERD), anxiety and depression, and chronic obstructive pulmonary disorder (COPD) are common in patients with severe asthma and add to the disease burden, wrote Mark C. Liu, MD, of Johns Hopkins University, Baltimore, and colleagues.

“Some comorbidities, such as CRSwNP, share pathophysiological mechanisms with severe asthma, with interleukin-5 (IL-5),” and treatments targeting IL-5 could improve outcomes, they said.

In the real-world REALITI-A study, mepolizumab, a humanized monoclonal antibody that targets IL-5, significantly reduced asthma exacerbation and oral corticosteroid use in severe asthma patients, they said.

To assess the impact of mepolizumab on patients with comorbidities, the researchers conducted a post hoc analysis of 822 adults with severe asthma, including 321 with CRSwNP, 309 with GERD, 203 with depression/anxiety, and 81 with COPD. The findings were published in the Journal of Allergy and Clinical Immunology: In Practice.

The main outcomes were the rate of clinically significant asthma exacerbations (CSEs) between the 12 months before and after mepolizumab initiation, and the changes from baseline in the daily maintenance use of oral corticosteroids (OCS).

Across all comorbidities, the rate of CSEs decreased significantly from the pretreatment period to the follow-up period, from 4.28 events per year to 1.23 events per year.

“A numerically greater reduction in the rate of CSEs was reported for patients with versus without CRSwNP, whereas the reverse was reported for patients with versus without COPD and depression/anxiety, although the confidence intervals were large for the with COPD subgroup,” the researchers wrote.

The median maintenance dose of oral corticosteroids decreased by at least 50% across all comorbidities after mepolizumab treatment; patients with CRSwNP had the greatest reduction (83%).

In addition, scores on the Asthma Control Questionnaire–5 decreased by at least 0.63 points, and least squared (LS) mean changes in forced expiratory volume per second (FEV₁) increased from baseline across all comorbidities after mepolizumab treatment by at least 74 mL.

Although patients with versus without CRSwNP had greater improvements, patients without GERD, depression/anxiety, and COPD had greater improvements than did those without the respective conditions with the exception of greater FEV₁ improvement in patients with vs. without COPD.

“Patients with severe asthma and comorbid CRSwNP are recognized as having a high disease burden, as demonstrated by more frequent exacerbations,” the researchers wrote in their discussion. “Mepolizumab may serve to reduce the disease burden of this high-risk group by targeting the common pathophysiological pathway of IL-5 and eosinophilic-driven inflammation because it has proven clinical benefits in treating asthma and CRSwNP separately and together,” and the current study findings support the use of mepolizumab for this population in particular, they said.

The findings were limited by several factors including the incomplete data for voluntary assessments, the post hoc design and relatively small numbers of patients in various subgroups, notably COPD, and the potential inaccurate diagnosis of COPD, the researchers noted.

“Nevertheless, because the amount of improvement in each outcome following mepolizumab treatment differed depending on the comorbidity in question, our findings highlight the impact that comorbidities and their prevalence and severity have on outcomes,” and the overall success of mepolizumab across clinical characteristics and comorbidities supports the generalizability of the findings to the larger population of adults with severe asthma, they concluded.

The study was supported by GlaxoSmithKline. Dr. Liu disclosed research funding from GSK, Boehringer Ingelheim, and Gossamer Bio, and participation on advisory boards for AstraZeneca, GSK, and Gossamer Bio.

Artificial intelligence chatbots can give accurate information to common questions about cancer but not so much when it comes to providing evidence-based cancer treatment recommendations, two new studies suggest.

AI chatbots, such as ChatGPT (OpenAI), are becoming go-to sources for health information. However, no studies have rigorously evaluated the quality of their medical advice, especially for cancer.

Two new studies published in JAMA Oncology did just that.

One, which looked at common cancer-related Google searches, found that AI chatbots generally provide accurate information to consumers, but the information’s usefulness may be limited by its complexity.

The other, which assessed cancer treatment recommendations, found that AI chatbots overall missed the mark on providing recommendations for breast, prostate, and lung cancers in line with national treatment guidelines.

The medical world is becoming “enamored with our newest potential helper, large language models (LLMs) and in particular chatbots, such as ChatGPT,” Atul Butte, MD, PhD, who heads the Bakar Computational Health Sciences Institute, University of California, San Francisco, wrote in an editorial accompanying the studies. “But maybe our core belief in GPT technology as a clinical partner has not sufficiently been earned yet.”

The first study by Alexander Pan of the State University of New York, Brooklyn, and colleagues analyzed the quality of responses to the top five most searched questions on skin, lung, breast, colorectal, and prostate cancer provided by four AI chatbots: ChatGPT-3.5, Perplexity (Perplexity.AI), Chatsonic (Writesonic), and Bing AI (Microsoft).

Questions included what is skin cancer and what are symptoms of prostate, lung, or breast cancer? The team rated the responses for quality, clarity, actionability, misinformation, and readability.

The researchers found that the four chatbots generated “high-quality” responses about the five cancers and did not appear to spread misinformation. Three of the four chatbots cited reputable sources, such as the American Cancer Society, Mayo Clinic, and Centers for Disease Controls and Prevention, which is “reassuring,” the researchers said.

However, the team also found that the usefulness of the information was “limited” because responses were often written at a college reading level. Another limitation: AI chatbots provided concise answers with no visual aids, which may not be sufficient to explain more complex ideas to consumers.

“These limitations suggest that AI chatbots should be used [supplementally] and not as a primary source for medical information,” the authors said, adding that the chatbots “typically acknowledged their limitations in providing individualized advice and encouraged users to seek medical attention.”

A related study in the journal highlighted the ability of AI chatbots to generate appropriate cancer treatment recommendations.

In this analysis, Shan Chen, MS, with the AI in Medicine Program, Mass General Brigham, Harvard Medical School, Boston, and colleagues benchmarked cancer treatment recommendations made by ChatGPT-3.5 against 2021 National Comprehensive Cancer Network guidelines.

The team created 104 prompts designed to elicit basic treatment strategies for various types of cancer, including breast, prostate, and lung cancer. Questions included “What is the treatment for stage I breast cancer?” Several oncologists then assessed the level of concordance between the chatbot responses and NCCN guidelines.

In 62% of the prompts and answers, all the recommended treatments aligned with the oncologists’ views.

The chatbot provided at least one guideline-concordant treatment for 98% of prompts. However, for 34% of prompts, the chatbot also recommended at least one nonconcordant treatment.

And about 13% of recommended treatments were “hallucinated,” that is, not part of any recommended treatment. Hallucinations were primarily recommendations for localized treatment of advanced disease, targeted therapy, or immunotherapy.

Based on the findings, the team recommended that clinicians advise patients that AI chatbots are not a reliable source of cancer treatment information.

“The chatbot did not perform well at providing accurate cancer treatment recommendations,” the authors said. “The chatbot was most likely to mix in incorrect recommendations among correct ones, an error difficult even for experts to detect.”

In his editorial, Dr. Butte highlighted several caveats, including that the teams evaluated “off the shelf” chatbots, which likely had no specific medical training, and the prompts

designed in both studies were very basic, which may have limited their specificity or actionability. Newer LLMs with specific health care training are being released, he explained.

Despite the mixed study findings, Dr. Butte remains optimistic about the future of AI in medicine.

“Today, the reality is that the highest-quality care is concentrated within a few premier medical systems like the NCI Comprehensive Cancer Centers, accessible only to a small fraction of the global population,” Dr. Butte explained. “However, AI has the potential to change this.”

How can we make this happen?

AI algorithms would need to be trained with “data from the best medical systems globally” and “the latest guidelines from NCCN and elsewhere.” Digital health platforms powered by AI could then be designed to provide resources and advice to patients around the globe, Dr. Butte said.

Although “these algorithms will need to be carefully monitored as they are brought into health systems,” Dr. Butte said, it does not change their potential to “improve care for both the haves and have-nots of health care.”

The study by Mr. Pan and colleagues had no specific funding; one author, Stacy Loeb, MD, MSc, PhD, reported a disclosure; no other disclosures were reported. The study by Shan Chen and colleagues was supported by the Woods Foundation; several authors reported disclosures outside the submitted work. Dr. Butte disclosed relationships with several pharmaceutical companies.

A version of this article first appeared on Medscape.com.

Artificial intelligence chatbots can give accurate information to common questions about cancer but not so much when it comes to providing evidence-based cancer treatment recommendations, two new studies suggest.

AI chatbots, such as ChatGPT (OpenAI), are becoming go-to sources for health information. However, no studies have rigorously evaluated the quality of their medical advice, especially for cancer.

Two new studies published in JAMA Oncology did just that.

One, which looked at common cancer-related Google searches, found that AI chatbots generally provide accurate information to consumers, but the information’s usefulness may be limited by its complexity.

The other, which assessed cancer treatment recommendations, found that AI chatbots overall missed the mark on providing recommendations for breast, prostate, and lung cancers in line with national treatment guidelines.

The medical world is becoming “enamored with our newest potential helper, large language models (LLMs) and in particular chatbots, such as ChatGPT,” Atul Butte, MD, PhD, who heads the Bakar Computational Health Sciences Institute, University of California, San Francisco, wrote in an editorial accompanying the studies. “But maybe our core belief in GPT technology as a clinical partner has not sufficiently been earned yet.”

The first study by Alexander Pan of the State University of New York, Brooklyn, and colleagues analyzed the quality of responses to the top five most searched questions on skin, lung, breast, colorectal, and prostate cancer provided by four AI chatbots: ChatGPT-3.5, Perplexity (Perplexity.AI), Chatsonic (Writesonic), and Bing AI (Microsoft).

Questions included what is skin cancer and what are symptoms of prostate, lung, or breast cancer? The team rated the responses for quality, clarity, actionability, misinformation, and readability.

The researchers found that the four chatbots generated “high-quality” responses about the five cancers and did not appear to spread misinformation. Three of the four chatbots cited reputable sources, such as the American Cancer Society, Mayo Clinic, and Centers for Disease Controls and Prevention, which is “reassuring,” the researchers said.

However, the team also found that the usefulness of the information was “limited” because responses were often written at a college reading level. Another limitation: AI chatbots provided concise answers with no visual aids, which may not be sufficient to explain more complex ideas to consumers.

“These limitations suggest that AI chatbots should be used [supplementally] and not as a primary source for medical information,” the authors said, adding that the chatbots “typically acknowledged their limitations in providing individualized advice and encouraged users to seek medical attention.”

A related study in the journal highlighted the ability of AI chatbots to generate appropriate cancer treatment recommendations.

In this analysis, Shan Chen, MS, with the AI in Medicine Program, Mass General Brigham, Harvard Medical School, Boston, and colleagues benchmarked cancer treatment recommendations made by ChatGPT-3.5 against 2021 National Comprehensive Cancer Network guidelines.

The team created 104 prompts designed to elicit basic treatment strategies for various types of cancer, including breast, prostate, and lung cancer. Questions included “What is the treatment for stage I breast cancer?” Several oncologists then assessed the level of concordance between the chatbot responses and NCCN guidelines.

In 62% of the prompts and answers, all the recommended treatments aligned with the oncologists’ views.

The chatbot provided at least one guideline-concordant treatment for 98% of prompts. However, for 34% of prompts, the chatbot also recommended at least one nonconcordant treatment.

And about 13% of recommended treatments were “hallucinated,” that is, not part of any recommended treatment. Hallucinations were primarily recommendations for localized treatment of advanced disease, targeted therapy, or immunotherapy.

Based on the findings, the team recommended that clinicians advise patients that AI chatbots are not a reliable source of cancer treatment information.

“The chatbot did not perform well at providing accurate cancer treatment recommendations,” the authors said. “The chatbot was most likely to mix in incorrect recommendations among correct ones, an error difficult even for experts to detect.”

In his editorial, Dr. Butte highlighted several caveats, including that the teams evaluated “off the shelf” chatbots, which likely had no specific medical training, and the prompts

designed in both studies were very basic, which may have limited their specificity or actionability. Newer LLMs with specific health care training are being released, he explained.

Despite the mixed study findings, Dr. Butte remains optimistic about the future of AI in medicine.

“Today, the reality is that the highest-quality care is concentrated within a few premier medical systems like the NCI Comprehensive Cancer Centers, accessible only to a small fraction of the global population,” Dr. Butte explained. “However, AI has the potential to change this.”

How can we make this happen?

AI algorithms would need to be trained with “data from the best medical systems globally” and “the latest guidelines from NCCN and elsewhere.” Digital health platforms powered by AI could then be designed to provide resources and advice to patients around the globe, Dr. Butte said.

Although “these algorithms will need to be carefully monitored as they are brought into health systems,” Dr. Butte said, it does not change their potential to “improve care for both the haves and have-nots of health care.”

The study by Mr. Pan and colleagues had no specific funding; one author, Stacy Loeb, MD, MSc, PhD, reported a disclosure; no other disclosures were reported. The study by Shan Chen and colleagues was supported by the Woods Foundation; several authors reported disclosures outside the submitted work. Dr. Butte disclosed relationships with several pharmaceutical companies.

A version of this article first appeared on Medscape.com.

Artificial intelligence chatbots can give accurate information to common questions about cancer but not so much when it comes to providing evidence-based cancer treatment recommendations, two new studies suggest.

AI chatbots, such as ChatGPT (OpenAI), are becoming go-to sources for health information. However, no studies have rigorously evaluated the quality of their medical advice, especially for cancer.

Two new studies published in JAMA Oncology did just that.

One, which looked at common cancer-related Google searches, found that AI chatbots generally provide accurate information to consumers, but the information’s usefulness may be limited by its complexity.

The other, which assessed cancer treatment recommendations, found that AI chatbots overall missed the mark on providing recommendations for breast, prostate, and lung cancers in line with national treatment guidelines.

The medical world is becoming “enamored with our newest potential helper, large language models (LLMs) and in particular chatbots, such as ChatGPT,” Atul Butte, MD, PhD, who heads the Bakar Computational Health Sciences Institute, University of California, San Francisco, wrote in an editorial accompanying the studies. “But maybe our core belief in GPT technology as a clinical partner has not sufficiently been earned yet.”

The first study by Alexander Pan of the State University of New York, Brooklyn, and colleagues analyzed the quality of responses to the top five most searched questions on skin, lung, breast, colorectal, and prostate cancer provided by four AI chatbots: ChatGPT-3.5, Perplexity (Perplexity.AI), Chatsonic (Writesonic), and Bing AI (Microsoft).

Questions included what is skin cancer and what are symptoms of prostate, lung, or breast cancer? The team rated the responses for quality, clarity, actionability, misinformation, and readability.

The researchers found that the four chatbots generated “high-quality” responses about the five cancers and did not appear to spread misinformation. Three of the four chatbots cited reputable sources, such as the American Cancer Society, Mayo Clinic, and Centers for Disease Controls and Prevention, which is “reassuring,” the researchers said.

However, the team also found that the usefulness of the information was “limited” because responses were often written at a college reading level. Another limitation: AI chatbots provided concise answers with no visual aids, which may not be sufficient to explain more complex ideas to consumers.

“These limitations suggest that AI chatbots should be used [supplementally] and not as a primary source for medical information,” the authors said, adding that the chatbots “typically acknowledged their limitations in providing individualized advice and encouraged users to seek medical attention.”

A related study in the journal highlighted the ability of AI chatbots to generate appropriate cancer treatment recommendations.

In this analysis, Shan Chen, MS, with the AI in Medicine Program, Mass General Brigham, Harvard Medical School, Boston, and colleagues benchmarked cancer treatment recommendations made by ChatGPT-3.5 against 2021 National Comprehensive Cancer Network guidelines.

The team created 104 prompts designed to elicit basic treatment strategies for various types of cancer, including breast, prostate, and lung cancer. Questions included “What is the treatment for stage I breast cancer?” Several oncologists then assessed the level of concordance between the chatbot responses and NCCN guidelines.

In 62% of the prompts and answers, all the recommended treatments aligned with the oncologists’ views.

The chatbot provided at least one guideline-concordant treatment for 98% of prompts. However, for 34% of prompts, the chatbot also recommended at least one nonconcordant treatment.

And about 13% of recommended treatments were “hallucinated,” that is, not part of any recommended treatment. Hallucinations were primarily recommendations for localized treatment of advanced disease, targeted therapy, or immunotherapy.

Based on the findings, the team recommended that clinicians advise patients that AI chatbots are not a reliable source of cancer treatment information.

“The chatbot did not perform well at providing accurate cancer treatment recommendations,” the authors said. “The chatbot was most likely to mix in incorrect recommendations among correct ones, an error difficult even for experts to detect.”

In his editorial, Dr. Butte highlighted several caveats, including that the teams evaluated “off the shelf” chatbots, which likely had no specific medical training, and the prompts

designed in both studies were very basic, which may have limited their specificity or actionability. Newer LLMs with specific health care training are being released, he explained.

Despite the mixed study findings, Dr. Butte remains optimistic about the future of AI in medicine.

“Today, the reality is that the highest-quality care is concentrated within a few premier medical systems like the NCI Comprehensive Cancer Centers, accessible only to a small fraction of the global population,” Dr. Butte explained. “However, AI has the potential to change this.”

How can we make this happen?

AI algorithms would need to be trained with “data from the best medical systems globally” and “the latest guidelines from NCCN and elsewhere.” Digital health platforms powered by AI could then be designed to provide resources and advice to patients around the globe, Dr. Butte said.

Although “these algorithms will need to be carefully monitored as they are brought into health systems,” Dr. Butte said, it does not change their potential to “improve care for both the haves and have-nots of health care.”

The study by Mr. Pan and colleagues had no specific funding; one author, Stacy Loeb, MD, MSc, PhD, reported a disclosure; no other disclosures were reported. The study by Shan Chen and colleagues was supported by the Woods Foundation; several authors reported disclosures outside the submitted work. Dr. Butte disclosed relationships with several pharmaceutical companies.

A version of this article first appeared on Medscape.com.

Depression and anxiety were not associated with outcomes for most cancer types, including breast cancer, prostate cancer, and alcohol-related cancer, according to findings from a large, individual participant data meta-analysis.

An exception was for lung and smoking-related cancers, but key covariates appeared to explain the relationship between depression, anxiety, and these cancer types, the investigators reported.

The findings challenge a common theory that depression and anxiety increase cancer risk and should “change current thinking,” they argue.

“Our results may come as a relief to many patients with cancer who believe their diagnosis is attributed to previous anxiety or depression,” first author Lonneke A. van Tuijl, PhD, of the University of Groningen and Utrecht University, the Netherlands, noted in a press release.

Analyses included data from up to nearly 320,000 individuals from the 18 prospective cohorts included in the international Psychosocial Factors and Cancer Incidence (PSY-CA) consortium. The cohorts are from studies conducted in the Netherlands, United Kingdom, Norway, and Canada, and included 25,803 patients with cancer. During follow-up of up to 26 years and more than 3.2 million person-years, depression and anxiety symptoms and diagnoses showed no association with overall breast, prostate, colorectal, and alcohol-related cancers (hazard ratios, 0.98-1.05).

For the specific cancer types, the investigators “found no evidence for an association between depression or anxiety and the incidence of colorectal cancer (HRs, 0.88-1.13), prostate cancer (HRs, 0.97-1.17), or alcohol-related cancers (HRs, 0.97-1.06).”

“For breast cancer, all pooled HRs were consistently negative but mean pooled HRs were close to 1 (HRs, 0.92-0.98) and the upper limit of the 95% confidence intervals all exceeded 1 (with the exception of anxiety symptoms),” they noted.

An increase in risk observed between depression and anxiety symptoms and diagnoses and lung cancer (HRs, 1.12-1.60) and smoking-related cancers (HRs, 1.06-1.60), in minimally adjusted models, was substantially attenuated after adjusting for known risk factors such as smoking, alcohol use, and body mass index (HRs, 1.04-1.08), the investigators reported.

The findings were published online in Cancer.

“Depression and anxiety have long been hypothesized to increase the risk for cancer. It is thought that the increased cancer risk can occur via several pathways, including health behaviors, or by influencing mutation, viral oncogenes, cell proliferation, or DNA repair,” the authors explained, noting that “[c]onclusions drawn in meta-analyses vary greatly, with some supporting an association between depression, anxiety, and cancer incidence and others finding no or a negligible association.”

The current findings “may help health professionals to alleviate feelings of guilt and self-blame in patients with cancer who attribute their diagnosis to previous depression or anxiety,” they said, noting that the findings “also underscore the importance of addressing tobacco smoking and other unhealthy behaviors – including those that may develop as a result of anxiety or depression.”

“However, further research is needed to understand exactly how depression, anxiety, health behaviors, and lung cancer are related,” said Dr. Tuijl.

Dr. Tuijl has received grants and travel support from the Dutch Cancer Society (KWF).
 

Depression and anxiety were not associated with outcomes for most cancer types, including breast cancer, prostate cancer, and alcohol-related cancer, according to findings from a large, individual participant data meta-analysis.

An exception was for lung and smoking-related cancers, but key covariates appeared to explain the relationship between depression, anxiety, and these cancer types, the investigators reported.

The findings challenge a common theory that depression and anxiety increase cancer risk and should “change current thinking,” they argue.

“Our results may come as a relief to many patients with cancer who believe their diagnosis is attributed to previous anxiety or depression,” first author Lonneke A. van Tuijl, PhD, of the University of Groningen and Utrecht University, the Netherlands, noted in a press release.

Analyses included data from up to nearly 320,000 individuals from the 18 prospective cohorts included in the international Psychosocial Factors and Cancer Incidence (PSY-CA) consortium. The cohorts are from studies conducted in the Netherlands, United Kingdom, Norway, and Canada, and included 25,803 patients with cancer. During follow-up of up to 26 years and more than 3.2 million person-years, depression and anxiety symptoms and diagnoses showed no association with overall breast, prostate, colorectal, and alcohol-related cancers (hazard ratios, 0.98-1.05).

For the specific cancer types, the investigators “found no evidence for an association between depression or anxiety and the incidence of colorectal cancer (HRs, 0.88-1.13), prostate cancer (HRs, 0.97-1.17), or alcohol-related cancers (HRs, 0.97-1.06).”

“For breast cancer, all pooled HRs were consistently negative but mean pooled HRs were close to 1 (HRs, 0.92-0.98) and the upper limit of the 95% confidence intervals all exceeded 1 (with the exception of anxiety symptoms),” they noted.

An increase in risk observed between depression and anxiety symptoms and diagnoses and lung cancer (HRs, 1.12-1.60) and smoking-related cancers (HRs, 1.06-1.60), in minimally adjusted models, was substantially attenuated after adjusting for known risk factors such as smoking, alcohol use, and body mass index (HRs, 1.04-1.08), the investigators reported.

The findings were published online in Cancer.

“Depression and anxiety have long been hypothesized to increase the risk for cancer. It is thought that the increased cancer risk can occur via several pathways, including health behaviors, or by influencing mutation, viral oncogenes, cell proliferation, or DNA repair,” the authors explained, noting that “[c]onclusions drawn in meta-analyses vary greatly, with some supporting an association between depression, anxiety, and cancer incidence and others finding no or a negligible association.”

The current findings “may help health professionals to alleviate feelings of guilt and self-blame in patients with cancer who attribute their diagnosis to previous depression or anxiety,” they said, noting that the findings “also underscore the importance of addressing tobacco smoking and other unhealthy behaviors – including those that may develop as a result of anxiety or depression.”

“However, further research is needed to understand exactly how depression, anxiety, health behaviors, and lung cancer are related,” said Dr. Tuijl.

Dr. Tuijl has received grants and travel support from the Dutch Cancer Society (KWF).
 

Depression and anxiety were not associated with outcomes for most cancer types, including breast cancer, prostate cancer, and alcohol-related cancer, according to findings from a large, individual participant data meta-analysis.

An exception was for lung and smoking-related cancers, but key covariates appeared to explain the relationship between depression, anxiety, and these cancer types, the investigators reported.

The findings challenge a common theory that depression and anxiety increase cancer risk and should “change current thinking,” they argue.

“Our results may come as a relief to many patients with cancer who believe their diagnosis is attributed to previous anxiety or depression,” first author Lonneke A. van Tuijl, PhD, of the University of Groningen and Utrecht University, the Netherlands, noted in a press release.

Analyses included data from up to nearly 320,000 individuals from the 18 prospective cohorts included in the international Psychosocial Factors and Cancer Incidence (PSY-CA) consortium. The cohorts are from studies conducted in the Netherlands, United Kingdom, Norway, and Canada, and included 25,803 patients with cancer. During follow-up of up to 26 years and more than 3.2 million person-years, depression and anxiety symptoms and diagnoses showed no association with overall breast, prostate, colorectal, and alcohol-related cancers (hazard ratios, 0.98-1.05).

For the specific cancer types, the investigators “found no evidence for an association between depression or anxiety and the incidence of colorectal cancer (HRs, 0.88-1.13), prostate cancer (HRs, 0.97-1.17), or alcohol-related cancers (HRs, 0.97-1.06).”

“For breast cancer, all pooled HRs were consistently negative but mean pooled HRs were close to 1 (HRs, 0.92-0.98) and the upper limit of the 95% confidence intervals all exceeded 1 (with the exception of anxiety symptoms),” they noted.

An increase in risk observed between depression and anxiety symptoms and diagnoses and lung cancer (HRs, 1.12-1.60) and smoking-related cancers (HRs, 1.06-1.60), in minimally adjusted models, was substantially attenuated after adjusting for known risk factors such as smoking, alcohol use, and body mass index (HRs, 1.04-1.08), the investigators reported.

The findings were published online in Cancer.

“Depression and anxiety have long been hypothesized to increase the risk for cancer. It is thought that the increased cancer risk can occur via several pathways, including health behaviors, or by influencing mutation, viral oncogenes, cell proliferation, or DNA repair,” the authors explained, noting that “[c]onclusions drawn in meta-analyses vary greatly, with some supporting an association between depression, anxiety, and cancer incidence and others finding no or a negligible association.”

The current findings “may help health professionals to alleviate feelings of guilt and self-blame in patients with cancer who attribute their diagnosis to previous depression or anxiety,” they said, noting that the findings “also underscore the importance of addressing tobacco smoking and other unhealthy behaviors – including those that may develop as a result of anxiety or depression.”

“However, further research is needed to understand exactly how depression, anxiety, health behaviors, and lung cancer are related,” said Dr. Tuijl.

Dr. Tuijl has received grants and travel support from the Dutch Cancer Society (KWF).