Lung Cancer

The majority of adult cigarette smokers in the United States try to quit each year, but there was little change in the rate of quit attempts from 2011 to 2017, according to the Centers for Disease Control and Prevention.

The median percentage of adult smokers who tried to quit cigarettes over the past year went from 64.9% in 2011 to 65.4% in 2017, CDC investigators reported in the Morbidity and Mortality Weekly Report, but the rate has gone down since 2014, when it reached 66.9%.

“The limited progress in increasing quit attempts … together with the variation in quit attempt prevalence among states, underscores the importance of enhanced efforts to motivate and help smokers to quit,” wrote Kimp Walton, MS, of the CDC’s National Center for Chronic Disease Prevention and Health Promotion and associates.

State-specific trends in quit-attempt rates reflected the national situation. The prevalence of past-year cessation attempts went up significantly in four states (Kansas, Louisiana, Virginia, and West Virginia) from 2011 to 2017, went down significantly in two states (New York and Tennessee), and did not change significantly in the other 44 states and the District of Columbia, they wrote.

In 2017, cigarette smokers in Connecticut were the most likely to have tried to quit in the past year, with a rate of 71.6%. The only other places with rates greater than 70% were Delaware, D.C., New Jersey, and Texas. The lowest quit-attempt rate that year, 58.6%, belonged to Wisconsin, with Iowa and Missouri the only other states under 60%, the investigators reported based on data from annual Behavioral Risk Factor Surveillance System surveys.


“Because most smokers make multiple quit attempts before succeeding, as many as 30 on average, tobacco dependence is viewed as a chronic, relapsing condition that requires repeated intervention. Smokers should be encouraged to keep trying to quit until they succeed, and health care providers should be encouraged to keep supporting smokers until they quit,” investigators wrote.

rfranki@mdedge.com

SOURCE: Walton K et al. MMWR. 2019 Jul 19;68(28):621-6.

The majority of adult cigarette smokers in the United States try to quit each year, but there was little change in the rate of quit attempts from 2011 to 2017, according to the Centers for Disease Control and Prevention.

The median percentage of adult smokers who tried to quit cigarettes over the past year went from 64.9% in 2011 to 65.4% in 2017, CDC investigators reported in the Morbidity and Mortality Weekly Report, but the rate has gone down since 2014, when it reached 66.9%.

“The limited progress in increasing quit attempts … together with the variation in quit attempt prevalence among states, underscores the importance of enhanced efforts to motivate and help smokers to quit,” wrote Kimp Walton, MS, of the CDC’s National Center for Chronic Disease Prevention and Health Promotion and associates.

State-specific trends in quit-attempt rates reflected the national situation. The prevalence of past-year cessation attempts went up significantly in four states (Kansas, Louisiana, Virginia, and West Virginia) from 2011 to 2017, went down significantly in two states (New York and Tennessee), and did not change significantly in the other 44 states and the District of Columbia, they wrote.

In 2017, cigarette smokers in Connecticut were the most likely to have tried to quit in the past year, with a rate of 71.6%. The only other places with rates greater than 70% were Delaware, D.C., New Jersey, and Texas. The lowest quit-attempt rate that year, 58.6%, belonged to Wisconsin, with Iowa and Missouri the only other states under 60%, the investigators reported based on data from annual Behavioral Risk Factor Surveillance System surveys.


“Because most smokers make multiple quit attempts before succeeding, as many as 30 on average, tobacco dependence is viewed as a chronic, relapsing condition that requires repeated intervention. Smokers should be encouraged to keep trying to quit until they succeed, and health care providers should be encouraged to keep supporting smokers until they quit,” investigators wrote.

rfranki@mdedge.com

SOURCE: Walton K et al. MMWR. 2019 Jul 19;68(28):621-6.

The majority of adult cigarette smokers in the United States try to quit each year, but there was little change in the rate of quit attempts from 2011 to 2017, according to the Centers for Disease Control and Prevention.

The median percentage of adult smokers who tried to quit cigarettes over the past year went from 64.9% in 2011 to 65.4% in 2017, CDC investigators reported in the Morbidity and Mortality Weekly Report, but the rate has gone down since 2014, when it reached 66.9%.

“The limited progress in increasing quit attempts … together with the variation in quit attempt prevalence among states, underscores the importance of enhanced efforts to motivate and help smokers to quit,” wrote Kimp Walton, MS, of the CDC’s National Center for Chronic Disease Prevention and Health Promotion and associates.

State-specific trends in quit-attempt rates reflected the national situation. The prevalence of past-year cessation attempts went up significantly in four states (Kansas, Louisiana, Virginia, and West Virginia) from 2011 to 2017, went down significantly in two states (New York and Tennessee), and did not change significantly in the other 44 states and the District of Columbia, they wrote.

In 2017, cigarette smokers in Connecticut were the most likely to have tried to quit in the past year, with a rate of 71.6%. The only other places with rates greater than 70% were Delaware, D.C., New Jersey, and Texas. The lowest quit-attempt rate that year, 58.6%, belonged to Wisconsin, with Iowa and Missouri the only other states under 60%, the investigators reported based on data from annual Behavioral Risk Factor Surveillance System surveys.


“Because most smokers make multiple quit attempts before succeeding, as many as 30 on average, tobacco dependence is viewed as a chronic, relapsing condition that requires repeated intervention. Smokers should be encouraged to keep trying to quit until they succeed, and health care providers should be encouraged to keep supporting smokers until they quit,” investigators wrote.

rfranki@mdedge.com

SOURCE: Walton K et al. MMWR. 2019 Jul 19;68(28):621-6.

Combination radiotherapy and pembrolizumab may improve clinical outcomes by means of synergy in the treatment of patients with non–small cell lung cancer (NSCLC), according to results from two recent studies.

“The best way to combine immunotherapy with ablative therapies in the curative setting is an area of active investigation,” wrote Joshua M. Bauml, MD, of the University of Pennsylvania, Philadelphia, and colleagues.

Dr. Bauml and colleagues recently reported the results of a phase 2 study exploring the addition of pembrolizumab following the completion of locally ablative therapy in patients with oligometastatic NSCLC in JAMA Oncology.

The single-arm trial included 51 patients who received intravenous pembrolizumab (200 mg every 21 days) for a total of 8 cycles within 4-12 weeks of local ablative therapy completion. Study participants were administered locally ablative therapy to all recognized sites of malignancy.

The researchers measured two primary efficacy outcomes: progression-free survival (PFS) from the initiation of ablative therapy and the PFS from initiation of pembrolizumab. Secondary endpoints were safety, quality of life, and overall survival (OS).

Among patients who received pembrolizumab after ablative therapy, the median PFS was 19.1 months (95% CI, 9.4-28.7 months), which was significantly longer than the historical outcome (median PFS, 6.6 months; P = .005). In addition, the 24-month OS was 77.5%. With respect to safety, no decrease in quality of life or new safety signals were reported in the study.

One key limitation of the study was the single-arm design. As a result, distinguishing the effects of pembrolizumab over ablative therapy alone is not possible with the present data.

“This study is the first to show improved outcomes for immunotherapy after locally ablative therapy in patients with oligometastatic NSCLC,” Dr. Bauml and his colleagues wrote.

In another phase 2 trial (PEMBRO-RT study) reported in the same issue, Willemijn S.M.E. Theelen, MD, of the Netherlands Cancer Institute in Amsterdam and colleagues examined the use of pembrolizumab after stereotactic body radiotherapy or pembrolizumab alone in patients with recurrent metastatic NSCLC.

“This study evaluates whether stereotactic body radiotherapy enhances the effect of immune checkpoint blockade,” wrote Dr. Theelen and colleagues.

The PEMBRO-RT study included 76 patients with recurrent metastatic NSCLC who were randomized to pembrolizumab following radiotherapy or pembrolizumab alone. Intravenous pembrolizumab was administered at 200 mg/kg every 3 weeks, with the first dose given within 7 days after completion of radiotherapy.

The primary outcome was the overall response rate (ORR) at 12 weeks. Secondary outcomes included OS, PFS, and safety.

Among patients who received pembrolizumab after radiotherapy versus pembrolizumab alone, the ORR at 12 weeks was 36% and 18%, respectively (P = .07). In addition, the median PFS and OS were not statistically significant (P = .19 and P = .16, respectively).

“Positive results were largely influenced by the PD-L1–negative subgroup, which had significantly improved progression-free survival and overall survival,” the researchers wrote.

With respect to safety, no differences in grade 3-5 adverse effects were observed between the treatment groups. In addition, no significant differences were seen in pulmonary toxicities.

One key limitation of the study was the lack of information regarding optimal radiotherapy dosing and schedule.

“The results of this study are encouraging, and further evaluation in a larger phase 2/3 trial is recommended,” Dr. Theelen and colleagues wrote.

Further studies are needed to fully understand the links between combination radiotherapy and pembrolizumab in patients with NSCLC.

The study by Dr. Bauml and colleagues was funded by the Abramson Cancer Center and Merck & Co. The authors reported financial affiliations with Amgen, AstraZeneca, Bristol-Myers Squibb, Celgene, Janssen, Takeda, and several others.

The study by Dr. Theelen and colleagues was funded by Merck Sharp & Dohme. The authors reported financial affiliations with AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Merck Sharp & Dohme, Roche, Takeda, and several others.
 

SOURCE: Bauml JM et al. JAMA Oncol. 2019 Jul 11. doi: 10.1001/jamaoncol.2019.1449. Theelen WSME et al. JAMA Oncol. 2019 Jul 11. doi: 10.1001/jamaoncol.2019.1478.

Combination radiotherapy and pembrolizumab may improve clinical outcomes by means of synergy in the treatment of patients with non–small cell lung cancer (NSCLC), according to results from two recent studies.

“The best way to combine immunotherapy with ablative therapies in the curative setting is an area of active investigation,” wrote Joshua M. Bauml, MD, of the University of Pennsylvania, Philadelphia, and colleagues.

Dr. Bauml and colleagues recently reported the results of a phase 2 study exploring the addition of pembrolizumab following the completion of locally ablative therapy in patients with oligometastatic NSCLC in JAMA Oncology.

The single-arm trial included 51 patients who received intravenous pembrolizumab (200 mg every 21 days) for a total of 8 cycles within 4-12 weeks of local ablative therapy completion. Study participants were administered locally ablative therapy to all recognized sites of malignancy.

The researchers measured two primary efficacy outcomes: progression-free survival (PFS) from the initiation of ablative therapy and the PFS from initiation of pembrolizumab. Secondary endpoints were safety, quality of life, and overall survival (OS).

Among patients who received pembrolizumab after ablative therapy, the median PFS was 19.1 months (95% CI, 9.4-28.7 months), which was significantly longer than the historical outcome (median PFS, 6.6 months; P = .005). In addition, the 24-month OS was 77.5%. With respect to safety, no decrease in quality of life or new safety signals were reported in the study.

One key limitation of the study was the single-arm design. As a result, distinguishing the effects of pembrolizumab over ablative therapy alone is not possible with the present data.

“This study is the first to show improved outcomes for immunotherapy after locally ablative therapy in patients with oligometastatic NSCLC,” Dr. Bauml and his colleagues wrote.

In another phase 2 trial (PEMBRO-RT study) reported in the same issue, Willemijn S.M.E. Theelen, MD, of the Netherlands Cancer Institute in Amsterdam and colleagues examined the use of pembrolizumab after stereotactic body radiotherapy or pembrolizumab alone in patients with recurrent metastatic NSCLC.

“This study evaluates whether stereotactic body radiotherapy enhances the effect of immune checkpoint blockade,” wrote Dr. Theelen and colleagues.

The PEMBRO-RT study included 76 patients with recurrent metastatic NSCLC who were randomized to pembrolizumab following radiotherapy or pembrolizumab alone. Intravenous pembrolizumab was administered at 200 mg/kg every 3 weeks, with the first dose given within 7 days after completion of radiotherapy.

The primary outcome was the overall response rate (ORR) at 12 weeks. Secondary outcomes included OS, PFS, and safety.

Among patients who received pembrolizumab after radiotherapy versus pembrolizumab alone, the ORR at 12 weeks was 36% and 18%, respectively (P = .07). In addition, the median PFS and OS were not statistically significant (P = .19 and P = .16, respectively).

“Positive results were largely influenced by the PD-L1–negative subgroup, which had significantly improved progression-free survival and overall survival,” the researchers wrote.

With respect to safety, no differences in grade 3-5 adverse effects were observed between the treatment groups. In addition, no significant differences were seen in pulmonary toxicities.

One key limitation of the study was the lack of information regarding optimal radiotherapy dosing and schedule.

“The results of this study are encouraging, and further evaluation in a larger phase 2/3 trial is recommended,” Dr. Theelen and colleagues wrote.

Further studies are needed to fully understand the links between combination radiotherapy and pembrolizumab in patients with NSCLC.

The study by Dr. Bauml and colleagues was funded by the Abramson Cancer Center and Merck & Co. The authors reported financial affiliations with Amgen, AstraZeneca, Bristol-Myers Squibb, Celgene, Janssen, Takeda, and several others.

The study by Dr. Theelen and colleagues was funded by Merck Sharp & Dohme. The authors reported financial affiliations with AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Merck Sharp & Dohme, Roche, Takeda, and several others.
 

SOURCE: Bauml JM et al. JAMA Oncol. 2019 Jul 11. doi: 10.1001/jamaoncol.2019.1449. Theelen WSME et al. JAMA Oncol. 2019 Jul 11. doi: 10.1001/jamaoncol.2019.1478.

Combination radiotherapy and pembrolizumab may improve clinical outcomes by means of synergy in the treatment of patients with non–small cell lung cancer (NSCLC), according to results from two recent studies.

“The best way to combine immunotherapy with ablative therapies in the curative setting is an area of active investigation,” wrote Joshua M. Bauml, MD, of the University of Pennsylvania, Philadelphia, and colleagues.

Dr. Bauml and colleagues recently reported the results of a phase 2 study exploring the addition of pembrolizumab following the completion of locally ablative therapy in patients with oligometastatic NSCLC in JAMA Oncology.

The single-arm trial included 51 patients who received intravenous pembrolizumab (200 mg every 21 days) for a total of 8 cycles within 4-12 weeks of local ablative therapy completion. Study participants were administered locally ablative therapy to all recognized sites of malignancy.

The researchers measured two primary efficacy outcomes: progression-free survival (PFS) from the initiation of ablative therapy and the PFS from initiation of pembrolizumab. Secondary endpoints were safety, quality of life, and overall survival (OS).

Among patients who received pembrolizumab after ablative therapy, the median PFS was 19.1 months (95% CI, 9.4-28.7 months), which was significantly longer than the historical outcome (median PFS, 6.6 months; P = .005). In addition, the 24-month OS was 77.5%. With respect to safety, no decrease in quality of life or new safety signals were reported in the study.

One key limitation of the study was the single-arm design. As a result, distinguishing the effects of pembrolizumab over ablative therapy alone is not possible with the present data.

“This study is the first to show improved outcomes for immunotherapy after locally ablative therapy in patients with oligometastatic NSCLC,” Dr. Bauml and his colleagues wrote.

In another phase 2 trial (PEMBRO-RT study) reported in the same issue, Willemijn S.M.E. Theelen, MD, of the Netherlands Cancer Institute in Amsterdam and colleagues examined the use of pembrolizumab after stereotactic body radiotherapy or pembrolizumab alone in patients with recurrent metastatic NSCLC.

“This study evaluates whether stereotactic body radiotherapy enhances the effect of immune checkpoint blockade,” wrote Dr. Theelen and colleagues.

The PEMBRO-RT study included 76 patients with recurrent metastatic NSCLC who were randomized to pembrolizumab following radiotherapy or pembrolizumab alone. Intravenous pembrolizumab was administered at 200 mg/kg every 3 weeks, with the first dose given within 7 days after completion of radiotherapy.

The primary outcome was the overall response rate (ORR) at 12 weeks. Secondary outcomes included OS, PFS, and safety.

Among patients who received pembrolizumab after radiotherapy versus pembrolizumab alone, the ORR at 12 weeks was 36% and 18%, respectively (P = .07). In addition, the median PFS and OS were not statistically significant (P = .19 and P = .16, respectively).

“Positive results were largely influenced by the PD-L1–negative subgroup, which had significantly improved progression-free survival and overall survival,” the researchers wrote.

With respect to safety, no differences in grade 3-5 adverse effects were observed between the treatment groups. In addition, no significant differences were seen in pulmonary toxicities.

One key limitation of the study was the lack of information regarding optimal radiotherapy dosing and schedule.

“The results of this study are encouraging, and further evaluation in a larger phase 2/3 trial is recommended,” Dr. Theelen and colleagues wrote.

Further studies are needed to fully understand the links between combination radiotherapy and pembrolizumab in patients with NSCLC.

The study by Dr. Bauml and colleagues was funded by the Abramson Cancer Center and Merck & Co. The authors reported financial affiliations with Amgen, AstraZeneca, Bristol-Myers Squibb, Celgene, Janssen, Takeda, and several others.

The study by Dr. Theelen and colleagues was funded by Merck Sharp & Dohme. The authors reported financial affiliations with AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Merck Sharp & Dohme, Roche, Takeda, and several others.
 

SOURCE: Bauml JM et al. JAMA Oncol. 2019 Jul 11. doi: 10.1001/jamaoncol.2019.1449. Theelen WSME et al. JAMA Oncol. 2019 Jul 11. doi: 10.1001/jamaoncol.2019.1478.

Researchers say they have identified potential prognostic markers and targets for treatment in patients with non–small cell lung cancer (NSCLC) and brain metastases (BM).

There was “substantial” concordance in driver mutations, such as EGFR and KRAS, between BM and primary tumor samples but greater genomic instability in BM samples, reported Hong-Sheng Wang, PhD, of Sun Yat-Sen University in Guangzhou, China, and colleagues.

PI3K signaling was significantly associated with an increased risk of BM, and CDKs and PIK3CA were “potential druggable mutations,” they reported in Cancer.

The researchers conducted a retrospective study of 61 Chinese patients with NSCLC and BM. The patients had adenocarcinoma (n = 50), squamous cell carcinoma (n = 3), and mixed subtypes (n = 8). Less than half of patients (n = 28) had stage IV disease at diagnosis, 36 had metachronous disease, and 25 had synchronous disease. All patients had undergone surgery, 33 had received chemoradiation, 26 had received no systemic treatment, and 5 had been treated with tyrosine kinase inhibitors.

The researchers performed next-generation sequencing on primary tumors and matched BM samples from the 61 patients, targeting 416 cancer-relevant genes.

Results showed high concordance between the primary and BM samples with regard to major driver mutations – 92% for EGFR, 82% for KRAS, and 83% for TP53 mutations.

For nearly half of patients (48%), all mutations found in primary tumor samples were also found in BM samples. In fact, 18% of patients had the same mutational profiles in lung and brain lesions.

Conversely, 30% of patients had more brain-specific mutations, 13% had more lung-specific mutations, 28% had mixed profiles, and 11% had completely unique mutational profiles in lung and brain lesions.

Compared with primary tumor samples, BM samples had a significantly higher frequency of copy number variations (P = .0002); alterations in CDKN2A/2B, CCND1, CDK4, and RB1 (P = .0019); and alterations in PIK3CA, PTEN, STK11, RICTOR, and NF2 (P = .0037).

Patients with activated PI3K signaling in their primary tumors had significantly shorter BM-free survival. The hazard ratio (adjusted for baseline clinicopathologic parameters) was 8.49 (P = .0005).

There was no significant difference in BM-free survival between EGFR-/KRAS-mutated patients and patients with wild-type EGFR/KRAS (P = .29). However, there was a trend toward shorter BM-free survival in patients with TP53 mutations (P = .15).

There was a trend toward shorter BM-free intervals in patients with an activated WNT pathway via CTNNB1 mutations (P = .22) or APC and AXIN2 mutations (P = .015). However, the researchers said these findings should be treated with caution due to a small sample size.

The National Natural Science Foundation of China and the Natural Science Foundation of Guangdong Province supported the research. The researchers disclosed relationships with Geneseeq Technology Inc. in Toronto and Nanjing Geneseeq Technology Inc.

SOURCE: Wang H et al. Cancer. 2019 Jul 9. doi: 10.1002/cncr.32372.

Researchers say they have identified potential prognostic markers and targets for treatment in patients with non–small cell lung cancer (NSCLC) and brain metastases (BM).

There was “substantial” concordance in driver mutations, such as EGFR and KRAS, between BM and primary tumor samples but greater genomic instability in BM samples, reported Hong-Sheng Wang, PhD, of Sun Yat-Sen University in Guangzhou, China, and colleagues.

PI3K signaling was significantly associated with an increased risk of BM, and CDKs and PIK3CA were “potential druggable mutations,” they reported in Cancer.

The researchers conducted a retrospective study of 61 Chinese patients with NSCLC and BM. The patients had adenocarcinoma (n = 50), squamous cell carcinoma (n = 3), and mixed subtypes (n = 8). Less than half of patients (n = 28) had stage IV disease at diagnosis, 36 had metachronous disease, and 25 had synchronous disease. All patients had undergone surgery, 33 had received chemoradiation, 26 had received no systemic treatment, and 5 had been treated with tyrosine kinase inhibitors.

The researchers performed next-generation sequencing on primary tumors and matched BM samples from the 61 patients, targeting 416 cancer-relevant genes.

Results showed high concordance between the primary and BM samples with regard to major driver mutations – 92% for EGFR, 82% for KRAS, and 83% for TP53 mutations.

For nearly half of patients (48%), all mutations found in primary tumor samples were also found in BM samples. In fact, 18% of patients had the same mutational profiles in lung and brain lesions.

Conversely, 30% of patients had more brain-specific mutations, 13% had more lung-specific mutations, 28% had mixed profiles, and 11% had completely unique mutational profiles in lung and brain lesions.

Compared with primary tumor samples, BM samples had a significantly higher frequency of copy number variations (P = .0002); alterations in CDKN2A/2B, CCND1, CDK4, and RB1 (P = .0019); and alterations in PIK3CA, PTEN, STK11, RICTOR, and NF2 (P = .0037).

Patients with activated PI3K signaling in their primary tumors had significantly shorter BM-free survival. The hazard ratio (adjusted for baseline clinicopathologic parameters) was 8.49 (P = .0005).

There was no significant difference in BM-free survival between EGFR-/KRAS-mutated patients and patients with wild-type EGFR/KRAS (P = .29). However, there was a trend toward shorter BM-free survival in patients with TP53 mutations (P = .15).

There was a trend toward shorter BM-free intervals in patients with an activated WNT pathway via CTNNB1 mutations (P = .22) or APC and AXIN2 mutations (P = .015). However, the researchers said these findings should be treated with caution due to a small sample size.

The National Natural Science Foundation of China and the Natural Science Foundation of Guangdong Province supported the research. The researchers disclosed relationships with Geneseeq Technology Inc. in Toronto and Nanjing Geneseeq Technology Inc.

SOURCE: Wang H et al. Cancer. 2019 Jul 9. doi: 10.1002/cncr.32372.

Researchers say they have identified potential prognostic markers and targets for treatment in patients with non–small cell lung cancer (NSCLC) and brain metastases (BM).

There was “substantial” concordance in driver mutations, such as EGFR and KRAS, between BM and primary tumor samples but greater genomic instability in BM samples, reported Hong-Sheng Wang, PhD, of Sun Yat-Sen University in Guangzhou, China, and colleagues.

PI3K signaling was significantly associated with an increased risk of BM, and CDKs and PIK3CA were “potential druggable mutations,” they reported in Cancer.

The researchers conducted a retrospective study of 61 Chinese patients with NSCLC and BM. The patients had adenocarcinoma (n = 50), squamous cell carcinoma (n = 3), and mixed subtypes (n = 8). Less than half of patients (n = 28) had stage IV disease at diagnosis, 36 had metachronous disease, and 25 had synchronous disease. All patients had undergone surgery, 33 had received chemoradiation, 26 had received no systemic treatment, and 5 had been treated with tyrosine kinase inhibitors.

The researchers performed next-generation sequencing on primary tumors and matched BM samples from the 61 patients, targeting 416 cancer-relevant genes.

Results showed high concordance between the primary and BM samples with regard to major driver mutations – 92% for EGFR, 82% for KRAS, and 83% for TP53 mutations.

For nearly half of patients (48%), all mutations found in primary tumor samples were also found in BM samples. In fact, 18% of patients had the same mutational profiles in lung and brain lesions.

Conversely, 30% of patients had more brain-specific mutations, 13% had more lung-specific mutations, 28% had mixed profiles, and 11% had completely unique mutational profiles in lung and brain lesions.

Compared with primary tumor samples, BM samples had a significantly higher frequency of copy number variations (P = .0002); alterations in CDKN2A/2B, CCND1, CDK4, and RB1 (P = .0019); and alterations in PIK3CA, PTEN, STK11, RICTOR, and NF2 (P = .0037).

Patients with activated PI3K signaling in their primary tumors had significantly shorter BM-free survival. The hazard ratio (adjusted for baseline clinicopathologic parameters) was 8.49 (P = .0005).

There was no significant difference in BM-free survival between EGFR-/KRAS-mutated patients and patients with wild-type EGFR/KRAS (P = .29). However, there was a trend toward shorter BM-free survival in patients with TP53 mutations (P = .15).

There was a trend toward shorter BM-free intervals in patients with an activated WNT pathway via CTNNB1 mutations (P = .22) or APC and AXIN2 mutations (P = .015). However, the researchers said these findings should be treated with caution due to a small sample size.

The National Natural Science Foundation of China and the Natural Science Foundation of Guangdong Province supported the research. The researchers disclosed relationships with Geneseeq Technology Inc. in Toronto and Nanjing Geneseeq Technology Inc.

SOURCE: Wang H et al. Cancer. 2019 Jul 9. doi: 10.1002/cncr.32372.

Adding the immune checkpoint inhibitor atezolizumab (Tecentriq) to doublet or triplet regimens as first-line treatment for nonsquamous non–small cell lung cancer (NSCLC) is not cost effective, even by a long shot, concluded a Markov modeling study.

Positive results of the IMpower150 trial led the Food and Drug Administration to approve and the National Comprehensive Cancer Network to recommend the combination of atezolizumab, bevacizumab, carboplatin, and paclitaxel (ABCP) as an option for selected patients in this setting, noted the investigators, led by XiaoMin Wan, PhD, of the department of pharmacy at the Second Xiangya Hospital and the Institute of Clinical Pharmacy, both at Central South University, Changsha, China.

“Although adding atezolizumab to the combination of bevacizumab and chemotherapy results in significantly higher survival in patients with metastatic NSCLC, the question of whether its price reflects its potential benefit remains unclear from a value standpoint,” they wrote.

Dr. Wan and colleagues developed a Markov model to compare the lifetime cost and effectiveness of various combinations – the quadruplet ABCP regimen, the triplet BCP regimen (bevacizumab, carboplatin, and paclitaxel), and the doublet CP regimen (carboplatin and paclitaxel) – when used as first‐line treatment for metastatic nonsquamous NSCLC.

ABCP yielded an additional 0.413 quality-adjusted life-years (QALYs) and 0.460 life-years, compared with BCP, and an additional 0.738 QALYs and 0.956 life-years, compared with CP. Respective incremental costs were $234,998 and $381,116, the investigators reported in Cancer.

Ultimately, ABCP had an incremental cost‐effectiveness ratio (ICER) of $568,967 per QALY, compared with BCP, and $516,114 per QALY, compared with CP – both of which far exceeded the conventional $100,000 ICER per QALY willingness-to-pay threshold.

Although atezolizumab targets programmed death–ligand 1 (PD-L1), the ICER improved only modestly to $464,703 per QALY when treatment was given only to patients having PD‐L1 expression of at least 50% on tumor cells or at least 10% on immune cells. Findings were similar when the duration of atezolizumab therapy was restricted to 2 years.

However, steep reductions in the costs of the two targeted agents altered results. Specifically, ABCP had an ICER of $99,786 and $162,441 per QALY, compared with BCP and CP, respectively, when the costs of atezolizumab and bevacizumab were reduced by 70%, and ABCP fell below the $100,000 willingness-to-pay threshold, compared with both regimens, when those costs were reduced by 83%.

“To our knowledge, the current study is the first cost-effectiveness analysis of ABCP, compared with BCP, in the first-line setting for patients with metastatic NSCLC,” Dr. Wan and colleagues noted. “From the perspective of the U.S. payer, ABCP is estimated not to be cost effective, compared with BCP or CP, in the first-line setting for patients with metastatic, nonsquamous NSCLC at a [willingness-to-pay] threshold of $100,000 per QALY.”

“Although ABCP is not considered to be cost effective, this does not mean that patients should receive the less-effective treatment strategy of BCP,” they cautioned, noting that recent cost-effectiveness data appear to favor the first-line combination of another immune checkpoint inhibitor, pembrolizumab (Keytruda), with chemotherapy instead. “A price reduction is warranted to make ABCP cost effective and affordable.”

Dr. Wan did not report any relevant conflicts of interest. The study was supported by grants from the National Natural Science Foundation of China and the research project of the Health and Family Planning Commission of Hunan province.

SOURCE: Wan X et al. Cancer. 2019 Jul 9. doi: 10.1002/cncr.32368.

Adding the immune checkpoint inhibitor atezolizumab (Tecentriq) to doublet or triplet regimens as first-line treatment for nonsquamous non–small cell lung cancer (NSCLC) is not cost effective, even by a long shot, concluded a Markov modeling study.

Positive results of the IMpower150 trial led the Food and Drug Administration to approve and the National Comprehensive Cancer Network to recommend the combination of atezolizumab, bevacizumab, carboplatin, and paclitaxel (ABCP) as an option for selected patients in this setting, noted the investigators, led by XiaoMin Wan, PhD, of the department of pharmacy at the Second Xiangya Hospital and the Institute of Clinical Pharmacy, both at Central South University, Changsha, China.

“Although adding atezolizumab to the combination of bevacizumab and chemotherapy results in significantly higher survival in patients with metastatic NSCLC, the question of whether its price reflects its potential benefit remains unclear from a value standpoint,” they wrote.

Dr. Wan and colleagues developed a Markov model to compare the lifetime cost and effectiveness of various combinations – the quadruplet ABCP regimen, the triplet BCP regimen (bevacizumab, carboplatin, and paclitaxel), and the doublet CP regimen (carboplatin and paclitaxel) – when used as first‐line treatment for metastatic nonsquamous NSCLC.

ABCP yielded an additional 0.413 quality-adjusted life-years (QALYs) and 0.460 life-years, compared with BCP, and an additional 0.738 QALYs and 0.956 life-years, compared with CP. Respective incremental costs were $234,998 and $381,116, the investigators reported in Cancer.

Ultimately, ABCP had an incremental cost‐effectiveness ratio (ICER) of $568,967 per QALY, compared with BCP, and $516,114 per QALY, compared with CP – both of which far exceeded the conventional $100,000 ICER per QALY willingness-to-pay threshold.

Although atezolizumab targets programmed death–ligand 1 (PD-L1), the ICER improved only modestly to $464,703 per QALY when treatment was given only to patients having PD‐L1 expression of at least 50% on tumor cells or at least 10% on immune cells. Findings were similar when the duration of atezolizumab therapy was restricted to 2 years.

However, steep reductions in the costs of the two targeted agents altered results. Specifically, ABCP had an ICER of $99,786 and $162,441 per QALY, compared with BCP and CP, respectively, when the costs of atezolizumab and bevacizumab were reduced by 70%, and ABCP fell below the $100,000 willingness-to-pay threshold, compared with both regimens, when those costs were reduced by 83%.

“To our knowledge, the current study is the first cost-effectiveness analysis of ABCP, compared with BCP, in the first-line setting for patients with metastatic NSCLC,” Dr. Wan and colleagues noted. “From the perspective of the U.S. payer, ABCP is estimated not to be cost effective, compared with BCP or CP, in the first-line setting for patients with metastatic, nonsquamous NSCLC at a [willingness-to-pay] threshold of $100,000 per QALY.”

“Although ABCP is not considered to be cost effective, this does not mean that patients should receive the less-effective treatment strategy of BCP,” they cautioned, noting that recent cost-effectiveness data appear to favor the first-line combination of another immune checkpoint inhibitor, pembrolizumab (Keytruda), with chemotherapy instead. “A price reduction is warranted to make ABCP cost effective and affordable.”

Dr. Wan did not report any relevant conflicts of interest. The study was supported by grants from the National Natural Science Foundation of China and the research project of the Health and Family Planning Commission of Hunan province.

SOURCE: Wan X et al. Cancer. 2019 Jul 9. doi: 10.1002/cncr.32368.

Adding the immune checkpoint inhibitor atezolizumab (Tecentriq) to doublet or triplet regimens as first-line treatment for nonsquamous non–small cell lung cancer (NSCLC) is not cost effective, even by a long shot, concluded a Markov modeling study.

Positive results of the IMpower150 trial led the Food and Drug Administration to approve and the National Comprehensive Cancer Network to recommend the combination of atezolizumab, bevacizumab, carboplatin, and paclitaxel (ABCP) as an option for selected patients in this setting, noted the investigators, led by XiaoMin Wan, PhD, of the department of pharmacy at the Second Xiangya Hospital and the Institute of Clinical Pharmacy, both at Central South University, Changsha, China.

“Although adding atezolizumab to the combination of bevacizumab and chemotherapy results in significantly higher survival in patients with metastatic NSCLC, the question of whether its price reflects its potential benefit remains unclear from a value standpoint,” they wrote.

Dr. Wan and colleagues developed a Markov model to compare the lifetime cost and effectiveness of various combinations – the quadruplet ABCP regimen, the triplet BCP regimen (bevacizumab, carboplatin, and paclitaxel), and the doublet CP regimen (carboplatin and paclitaxel) – when used as first‐line treatment for metastatic nonsquamous NSCLC.

ABCP yielded an additional 0.413 quality-adjusted life-years (QALYs) and 0.460 life-years, compared with BCP, and an additional 0.738 QALYs and 0.956 life-years, compared with CP. Respective incremental costs were $234,998 and $381,116, the investigators reported in Cancer.

Ultimately, ABCP had an incremental cost‐effectiveness ratio (ICER) of $568,967 per QALY, compared with BCP, and $516,114 per QALY, compared with CP – both of which far exceeded the conventional $100,000 ICER per QALY willingness-to-pay threshold.

Although atezolizumab targets programmed death–ligand 1 (PD-L1), the ICER improved only modestly to $464,703 per QALY when treatment was given only to patients having PD‐L1 expression of at least 50% on tumor cells or at least 10% on immune cells. Findings were similar when the duration of atezolizumab therapy was restricted to 2 years.

However, steep reductions in the costs of the two targeted agents altered results. Specifically, ABCP had an ICER of $99,786 and $162,441 per QALY, compared with BCP and CP, respectively, when the costs of atezolizumab and bevacizumab were reduced by 70%, and ABCP fell below the $100,000 willingness-to-pay threshold, compared with both regimens, when those costs were reduced by 83%.

“To our knowledge, the current study is the first cost-effectiveness analysis of ABCP, compared with BCP, in the first-line setting for patients with metastatic NSCLC,” Dr. Wan and colleagues noted. “From the perspective of the U.S. payer, ABCP is estimated not to be cost effective, compared with BCP or CP, in the first-line setting for patients with metastatic, nonsquamous NSCLC at a [willingness-to-pay] threshold of $100,000 per QALY.”

“Although ABCP is not considered to be cost effective, this does not mean that patients should receive the less-effective treatment strategy of BCP,” they cautioned, noting that recent cost-effectiveness data appear to favor the first-line combination of another immune checkpoint inhibitor, pembrolizumab (Keytruda), with chemotherapy instead. “A price reduction is warranted to make ABCP cost effective and affordable.”

Dr. Wan did not report any relevant conflicts of interest. The study was supported by grants from the National Natural Science Foundation of China and the research project of the Health and Family Planning Commission of Hunan province.

SOURCE: Wan X et al. Cancer. 2019 Jul 9. doi: 10.1002/cncr.32368.

A combination of pembrolizumab and platinum chemotherapy is the most effective frontline treatment for patients with non–small cell lung cancer (NSCLC), according to a retrospective analysis of more than 16,000 patients.

The study showed that responses to therapy are best predicted by an aggregate of tumor mutational burden (TMB), programmed cell death ligand 1 (PD-L1) expression, and proportion of CD8+ T-cell tumor-infiltrating lymphocytes (TILs), reported Yunfang Yu, MD, of Sun Yat-sen University, Guangzhou, China, and colleagues.

“[I]mmunotherapy has produced inconsistent results in previous randomized clinical trials,” the investigators wrote, citing inconsistent survival outcomes in CheckMate-026 and publications by Takayama and Wu. “Moreover, independent immune-related biomarkers that are currently used, such as PD-L1 and TMB, have achieved clinical relevance for a selection of patients to some extent, but to our knowledge, they are still far from clear and established.” The report is in JAMA Network Open.

To gain clarity, the investigators performed a large-scale meta-analysis (n = 14,395) and individual patient-level study (n = 1,833) involving patients with NSCLC. Data were drawn from a variety of sources, including PubMed, EMBASE, Cochrane, conference proceedings, and others. Primary outcomes were median overall survival and progression-free survival. Secondary outcomes were objective response rate and durable clinical benefit. The Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) was used as a reporting guideline.

Analysis showed the superiority of immunotherapy to conventional therapy with significantly extended median overall survival and progression-free survival, both with an immunotherapy-favoring hazard ratio (HR) of 0.76 (P less than .001). Immunotherapy survival advantages were also reported individually for checkpoint inhibitors (HR, 0.75), tumor vaccines (HR, 0.83), and cellular immunotherapy (HR, 0.40). Of these three, checkpoint inhibitors and tumor vaccines showed superiority for progression-free survival. For first-line therapy, a combination of a pembrolizumab and chemotherapy was associated with better progression-free and overall survival than were other immunotherapies.

For patients treated with checkpoint inhibitors, higher levels of PD-L1 expression, TMB, or neo-antigen burden (NAB) were each prognostically valuable; however, the most powerful predictive tool was a combination of PD-L1 expression, TMB, and proportion of CD8+ T-cell TILs, with a 3-year overall survival area under the curve of 0.659. In addition, RYR1 and MGAM mutations were independently associated with durable clinical benefits.

“Future development of an optimized, integrated predictive model for immunotherapy should consider the integration of multiple approaches involving biomarkers associated with the T cell–inflamed tumor microenvironment, such as PD-L1 expression, ICs, and those associated with tumor neoepitope burden,” the investigators wrote.

The study was funded by the National Natural Science Foundation of China, Natural Science Foundation of Guangdong Province, and Guangzhou Science and Technology Program. The investigators disclosed no conflicts of interest.

SOURCE: Yu et al. JAMA Open. 2019 Jul 10. doi: 10.1001/jamanetworkopen.2019.6879.

A combination of pembrolizumab and platinum chemotherapy is the most effective frontline treatment for patients with non–small cell lung cancer (NSCLC), according to a retrospective analysis of more than 16,000 patients.

The study showed that responses to therapy are best predicted by an aggregate of tumor mutational burden (TMB), programmed cell death ligand 1 (PD-L1) expression, and proportion of CD8+ T-cell tumor-infiltrating lymphocytes (TILs), reported Yunfang Yu, MD, of Sun Yat-sen University, Guangzhou, China, and colleagues.

“[I]mmunotherapy has produced inconsistent results in previous randomized clinical trials,” the investigators wrote, citing inconsistent survival outcomes in CheckMate-026 and publications by Takayama and Wu. “Moreover, independent immune-related biomarkers that are currently used, such as PD-L1 and TMB, have achieved clinical relevance for a selection of patients to some extent, but to our knowledge, they are still far from clear and established.” The report is in JAMA Network Open.

To gain clarity, the investigators performed a large-scale meta-analysis (n = 14,395) and individual patient-level study (n = 1,833) involving patients with NSCLC. Data were drawn from a variety of sources, including PubMed, EMBASE, Cochrane, conference proceedings, and others. Primary outcomes were median overall survival and progression-free survival. Secondary outcomes were objective response rate and durable clinical benefit. The Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) was used as a reporting guideline.

Analysis showed the superiority of immunotherapy to conventional therapy with significantly extended median overall survival and progression-free survival, both with an immunotherapy-favoring hazard ratio (HR) of 0.76 (P less than .001). Immunotherapy survival advantages were also reported individually for checkpoint inhibitors (HR, 0.75), tumor vaccines (HR, 0.83), and cellular immunotherapy (HR, 0.40). Of these three, checkpoint inhibitors and tumor vaccines showed superiority for progression-free survival. For first-line therapy, a combination of a pembrolizumab and chemotherapy was associated with better progression-free and overall survival than were other immunotherapies.

For patients treated with checkpoint inhibitors, higher levels of PD-L1 expression, TMB, or neo-antigen burden (NAB) were each prognostically valuable; however, the most powerful predictive tool was a combination of PD-L1 expression, TMB, and proportion of CD8+ T-cell TILs, with a 3-year overall survival area under the curve of 0.659. In addition, RYR1 and MGAM mutations were independently associated with durable clinical benefits.

“Future development of an optimized, integrated predictive model for immunotherapy should consider the integration of multiple approaches involving biomarkers associated with the T cell–inflamed tumor microenvironment, such as PD-L1 expression, ICs, and those associated with tumor neoepitope burden,” the investigators wrote.

The study was funded by the National Natural Science Foundation of China, Natural Science Foundation of Guangdong Province, and Guangzhou Science and Technology Program. The investigators disclosed no conflicts of interest.

SOURCE: Yu et al. JAMA Open. 2019 Jul 10. doi: 10.1001/jamanetworkopen.2019.6879.

A combination of pembrolizumab and platinum chemotherapy is the most effective frontline treatment for patients with non–small cell lung cancer (NSCLC), according to a retrospective analysis of more than 16,000 patients.

The study showed that responses to therapy are best predicted by an aggregate of tumor mutational burden (TMB), programmed cell death ligand 1 (PD-L1) expression, and proportion of CD8+ T-cell tumor-infiltrating lymphocytes (TILs), reported Yunfang Yu, MD, of Sun Yat-sen University, Guangzhou, China, and colleagues.

“[I]mmunotherapy has produced inconsistent results in previous randomized clinical trials,” the investigators wrote, citing inconsistent survival outcomes in CheckMate-026 and publications by Takayama and Wu. “Moreover, independent immune-related biomarkers that are currently used, such as PD-L1 and TMB, have achieved clinical relevance for a selection of patients to some extent, but to our knowledge, they are still far from clear and established.” The report is in JAMA Network Open.

To gain clarity, the investigators performed a large-scale meta-analysis (n = 14,395) and individual patient-level study (n = 1,833) involving patients with NSCLC. Data were drawn from a variety of sources, including PubMed, EMBASE, Cochrane, conference proceedings, and others. Primary outcomes were median overall survival and progression-free survival. Secondary outcomes were objective response rate and durable clinical benefit. The Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) was used as a reporting guideline.

Analysis showed the superiority of immunotherapy to conventional therapy with significantly extended median overall survival and progression-free survival, both with an immunotherapy-favoring hazard ratio (HR) of 0.76 (P less than .001). Immunotherapy survival advantages were also reported individually for checkpoint inhibitors (HR, 0.75), tumor vaccines (HR, 0.83), and cellular immunotherapy (HR, 0.40). Of these three, checkpoint inhibitors and tumor vaccines showed superiority for progression-free survival. For first-line therapy, a combination of a pembrolizumab and chemotherapy was associated with better progression-free and overall survival than were other immunotherapies.

For patients treated with checkpoint inhibitors, higher levels of PD-L1 expression, TMB, or neo-antigen burden (NAB) were each prognostically valuable; however, the most powerful predictive tool was a combination of PD-L1 expression, TMB, and proportion of CD8+ T-cell TILs, with a 3-year overall survival area under the curve of 0.659. In addition, RYR1 and MGAM mutations were independently associated with durable clinical benefits.

“Future development of an optimized, integrated predictive model for immunotherapy should consider the integration of multiple approaches involving biomarkers associated with the T cell–inflamed tumor microenvironment, such as PD-L1 expression, ICs, and those associated with tumor neoepitope burden,” the investigators wrote.

The study was funded by the National Natural Science Foundation of China, Natural Science Foundation of Guangdong Province, and Guangzhou Science and Technology Program. The investigators disclosed no conflicts of interest.

SOURCE: Yu et al. JAMA Open. 2019 Jul 10. doi: 10.1001/jamanetworkopen.2019.6879.

In this edition of “How I will treat my next patient,” I take a look at recent studies that examined ways to predict important outcomes in two very different settings, acute leukemia and advanced non–small cell lung cancer (NSCLC). They share the virtue of helping cancer specialists to increase their vigilance for clinically relevant complications and situations and to educate patients and families.

VTE risk in acute leukemia

The risk of venous thromboembolism (VTE) in cancer patients depends upon multiple patient-, tumor-, anatomic-, and treatment-related factors. The Khorana score has become an accepted standard for predicting the risks of VTE and assessing the relative value of various anticoagulants in cancer patients. However, the only hematologic malignancy that is specifically listed among the primary cancer sites in the Khorana score is “lymphoma.” VTE can develop during treatment for acute leukemia, especially among patients with acute lymphoblastic leukemia (ALL).

At the 2019 annual congress of the European Hematology Association, Alejandro Lazo-Langer, MD, and his colleagues proposed a scoring system to quantify the risks of VTE based on a retrospective cohort study of more than 500 acute leukemia patients, diagnosed from 2006-2017. They identified 77 patients with a VTE event, with a median time from diagnosis to VTE of 64 days. Among 20 possible predictive factors, 3 emerged in the final multivariate model – platelet count greater than 50,000 (1 point), ALL (2 points), and prior history of VTE (3 points).

Over a period of 12 months, patients with a score of more than 3 points had a cumulative incidence of VTE of 44%, in comparison with 10.5% among patients with lower scores. They were unable to discern whether particular antineoplastic regimens or drugs enhanced the risk.

The authors proposed that, if verified in a validation cohort study, the scoring system could lead to better patient education about signs and symptoms, more intensive surveillance for high-risk patients, and preventive interventions.

What this means in practice

Although a large number of patient records were reviewed for Dr. Lazo-Langer’s study, there were just 74 ALL patients, and it is unclear whether particular treatment regimens or drugs (such as L-asparaginase in ALL) enhance risk. Further study with a validation cohort (as was performed for the Khorana score for patients with other malignancies), is warranted. The study is thought provoking, but for now, in my opinion, standard clinical vigilance, surveillance, and education regarding VTE in leukemia patients remain appropriate.

Steroid impact in NSCLC with ICI therapy

Patients with autoimmune disease and individuals requiring active treatment with steroids (prednisone at 10 mg/day or more or the equivalent) were excluded from clinical trials that led to Food and Drug Administration approval of immune checkpoint inhibitor (ICI) agents. Recently published data indicate that treatment with 10 mg or more of daily prednisone correlates with poor outcome in NSCLC patients receiving ICI therapy (J Clin Oncol. 2018;36:2872-8; J Thoracic Oncol. 2018;13:1771-5). However, at the 2019 annual meeting of the American Society of Clinical Oncology, analyses of the CancerLinQ database showed that, among NSCLC patients, autoimmune disease and treatment for autoimmune disease are surprisingly prevalent. Should oncologists refuse to treat these patients with ICI agents, alone and in combination with chemotherapy or CTLA4 inhibitors?

Biagio Ricciuti, MD, and colleagues published a retrospective, single-institution record review of 650 advanced NSCLC patients who were treated with ICI plus or minus CTLA-4 inhibition on a correlative intramural research study. Patients who received ICI with concurrent cytotoxic chemotherapy were excluded. They gathered clinical-pathologic information about whether patients received concurrent corticosteroids (10 mg/day or more vs. less than 10 mg/day of prednisone or the equivalent) and the reason for steroid use (oncologic vs. cancer-unrelated indications).

Importantly, they gathered information about programmed death-ligand 1 (PD-L1) tumor proportion scores and tumor mutational burden.

Among the 14.3% patients receiving prednisone 10 mg/day or more at the start of ICI therapy, progression-free survival and overall survival were significantly worse – but only among the 66 patients who needed steroids for oncologic reasons (pain, brain metastases, anorexia, cancer-associated dyspnea). Among the 27 patients who received steroids for cancer-unrelated reasons (autoimmune disease, chronic obstructive pulmonary disease, hypersensitivity pneumonitis), progression-free and overall survival were no different than for patients on prednisone 0-9 mg/day. Imbalances in PD-L1 tumor proportion scores among the groups analyzed did not clearly account for the differences in survival.

What this means in practice

The potential for great treatment outcomes with single-agent ICIs in a subset of advanced NSCLC patients, coupled with the lack of an air-tight biomarker for benefit, has changed the timing of discussions between oncologists and patients about stopping antineoplastic treatment. Since we cannot identify the patients for whom ICI use is futile, the default position has been lenient on using these expensive and potentially toxic therapies.

If verified in a multi-institutional setting, with larger numbers of NSCLC patients receiving steroids for cancer-unrelated reasons, the observations of Dr. Ricciuti and colleagues could help clinicians confidently identify the time to focus discussions on supportive care only. In patients with short survival and strong rationale for maximizing supportive care, analyses like this one could help us deliver more appropriate treatment, instead of more treatment, thereby furthering the goals of personalized cancer patient management.
 

Dr. Lyss has been a community-based medical oncologist and clinical researcher for more than 35 years, practicing in St. Louis. His clinical and research interests are in the prevention, diagnosis, and treatment of breast and lung cancers and in expanding access to clinical trials to medically underserved populations.

In this edition of “How I will treat my next patient,” I take a look at recent studies that examined ways to predict important outcomes in two very different settings, acute leukemia and advanced non–small cell lung cancer (NSCLC). They share the virtue of helping cancer specialists to increase their vigilance for clinically relevant complications and situations and to educate patients and families.

VTE risk in acute leukemia

The risk of venous thromboembolism (VTE) in cancer patients depends upon multiple patient-, tumor-, anatomic-, and treatment-related factors. The Khorana score has become an accepted standard for predicting the risks of VTE and assessing the relative value of various anticoagulants in cancer patients. However, the only hematologic malignancy that is specifically listed among the primary cancer sites in the Khorana score is “lymphoma.” VTE can develop during treatment for acute leukemia, especially among patients with acute lymphoblastic leukemia (ALL).

At the 2019 annual congress of the European Hematology Association, Alejandro Lazo-Langer, MD, and his colleagues proposed a scoring system to quantify the risks of VTE based on a retrospective cohort study of more than 500 acute leukemia patients, diagnosed from 2006-2017. They identified 77 patients with a VTE event, with a median time from diagnosis to VTE of 64 days. Among 20 possible predictive factors, 3 emerged in the final multivariate model – platelet count greater than 50,000 (1 point), ALL (2 points), and prior history of VTE (3 points).

Over a period of 12 months, patients with a score of more than 3 points had a cumulative incidence of VTE of 44%, in comparison with 10.5% among patients with lower scores. They were unable to discern whether particular antineoplastic regimens or drugs enhanced the risk.

The authors proposed that, if verified in a validation cohort study, the scoring system could lead to better patient education about signs and symptoms, more intensive surveillance for high-risk patients, and preventive interventions.

What this means in practice

Although a large number of patient records were reviewed for Dr. Lazo-Langer’s study, there were just 74 ALL patients, and it is unclear whether particular treatment regimens or drugs (such as L-asparaginase in ALL) enhance risk. Further study with a validation cohort (as was performed for the Khorana score for patients with other malignancies), is warranted. The study is thought provoking, but for now, in my opinion, standard clinical vigilance, surveillance, and education regarding VTE in leukemia patients remain appropriate.

Steroid impact in NSCLC with ICI therapy

Patients with autoimmune disease and individuals requiring active treatment with steroids (prednisone at 10 mg/day or more or the equivalent) were excluded from clinical trials that led to Food and Drug Administration approval of immune checkpoint inhibitor (ICI) agents. Recently published data indicate that treatment with 10 mg or more of daily prednisone correlates with poor outcome in NSCLC patients receiving ICI therapy (J Clin Oncol. 2018;36:2872-8; J Thoracic Oncol. 2018;13:1771-5). However, at the 2019 annual meeting of the American Society of Clinical Oncology, analyses of the CancerLinQ database showed that, among NSCLC patients, autoimmune disease and treatment for autoimmune disease are surprisingly prevalent. Should oncologists refuse to treat these patients with ICI agents, alone and in combination with chemotherapy or CTLA4 inhibitors?

Biagio Ricciuti, MD, and colleagues published a retrospective, single-institution record review of 650 advanced NSCLC patients who were treated with ICI plus or minus CTLA-4 inhibition on a correlative intramural research study. Patients who received ICI with concurrent cytotoxic chemotherapy were excluded. They gathered clinical-pathologic information about whether patients received concurrent corticosteroids (10 mg/day or more vs. less than 10 mg/day of prednisone or the equivalent) and the reason for steroid use (oncologic vs. cancer-unrelated indications).

Importantly, they gathered information about programmed death-ligand 1 (PD-L1) tumor proportion scores and tumor mutational burden.

Among the 14.3% patients receiving prednisone 10 mg/day or more at the start of ICI therapy, progression-free survival and overall survival were significantly worse – but only among the 66 patients who needed steroids for oncologic reasons (pain, brain metastases, anorexia, cancer-associated dyspnea). Among the 27 patients who received steroids for cancer-unrelated reasons (autoimmune disease, chronic obstructive pulmonary disease, hypersensitivity pneumonitis), progression-free and overall survival were no different than for patients on prednisone 0-9 mg/day. Imbalances in PD-L1 tumor proportion scores among the groups analyzed did not clearly account for the differences in survival.

What this means in practice

The potential for great treatment outcomes with single-agent ICIs in a subset of advanced NSCLC patients, coupled with the lack of an air-tight biomarker for benefit, has changed the timing of discussions between oncologists and patients about stopping antineoplastic treatment. Since we cannot identify the patients for whom ICI use is futile, the default position has been lenient on using these expensive and potentially toxic therapies.

If verified in a multi-institutional setting, with larger numbers of NSCLC patients receiving steroids for cancer-unrelated reasons, the observations of Dr. Ricciuti and colleagues could help clinicians confidently identify the time to focus discussions on supportive care only. In patients with short survival and strong rationale for maximizing supportive care, analyses like this one could help us deliver more appropriate treatment, instead of more treatment, thereby furthering the goals of personalized cancer patient management.
 

Dr. Lyss has been a community-based medical oncologist and clinical researcher for more than 35 years, practicing in St. Louis. His clinical and research interests are in the prevention, diagnosis, and treatment of breast and lung cancers and in expanding access to clinical trials to medically underserved populations.

In this edition of “How I will treat my next patient,” I take a look at recent studies that examined ways to predict important outcomes in two very different settings, acute leukemia and advanced non–small cell lung cancer (NSCLC). They share the virtue of helping cancer specialists to increase their vigilance for clinically relevant complications and situations and to educate patients and families.

VTE risk in acute leukemia

The risk of venous thromboembolism (VTE) in cancer patients depends upon multiple patient-, tumor-, anatomic-, and treatment-related factors. The Khorana score has become an accepted standard for predicting the risks of VTE and assessing the relative value of various anticoagulants in cancer patients. However, the only hematologic malignancy that is specifically listed among the primary cancer sites in the Khorana score is “lymphoma.” VTE can develop during treatment for acute leukemia, especially among patients with acute lymphoblastic leukemia (ALL).

At the 2019 annual congress of the European Hematology Association, Alejandro Lazo-Langer, MD, and his colleagues proposed a scoring system to quantify the risks of VTE based on a retrospective cohort study of more than 500 acute leukemia patients, diagnosed from 2006-2017. They identified 77 patients with a VTE event, with a median time from diagnosis to VTE of 64 days. Among 20 possible predictive factors, 3 emerged in the final multivariate model – platelet count greater than 50,000 (1 point), ALL (2 points), and prior history of VTE (3 points).

Over a period of 12 months, patients with a score of more than 3 points had a cumulative incidence of VTE of 44%, in comparison with 10.5% among patients with lower scores. They were unable to discern whether particular antineoplastic regimens or drugs enhanced the risk.

The authors proposed that, if verified in a validation cohort study, the scoring system could lead to better patient education about signs and symptoms, more intensive surveillance for high-risk patients, and preventive interventions.

What this means in practice

Although a large number of patient records were reviewed for Dr. Lazo-Langer’s study, there were just 74 ALL patients, and it is unclear whether particular treatment regimens or drugs (such as L-asparaginase in ALL) enhance risk. Further study with a validation cohort (as was performed for the Khorana score for patients with other malignancies), is warranted. The study is thought provoking, but for now, in my opinion, standard clinical vigilance, surveillance, and education regarding VTE in leukemia patients remain appropriate.

Steroid impact in NSCLC with ICI therapy

Patients with autoimmune disease and individuals requiring active treatment with steroids (prednisone at 10 mg/day or more or the equivalent) were excluded from clinical trials that led to Food and Drug Administration approval of immune checkpoint inhibitor (ICI) agents. Recently published data indicate that treatment with 10 mg or more of daily prednisone correlates with poor outcome in NSCLC patients receiving ICI therapy (J Clin Oncol. 2018;36:2872-8; J Thoracic Oncol. 2018;13:1771-5). However, at the 2019 annual meeting of the American Society of Clinical Oncology, analyses of the CancerLinQ database showed that, among NSCLC patients, autoimmune disease and treatment for autoimmune disease are surprisingly prevalent. Should oncologists refuse to treat these patients with ICI agents, alone and in combination with chemotherapy or CTLA4 inhibitors?

Biagio Ricciuti, MD, and colleagues published a retrospective, single-institution record review of 650 advanced NSCLC patients who were treated with ICI plus or minus CTLA-4 inhibition on a correlative intramural research study. Patients who received ICI with concurrent cytotoxic chemotherapy were excluded. They gathered clinical-pathologic information about whether patients received concurrent corticosteroids (10 mg/day or more vs. less than 10 mg/day of prednisone or the equivalent) and the reason for steroid use (oncologic vs. cancer-unrelated indications).

Importantly, they gathered information about programmed death-ligand 1 (PD-L1) tumor proportion scores and tumor mutational burden.

Among the 14.3% patients receiving prednisone 10 mg/day or more at the start of ICI therapy, progression-free survival and overall survival were significantly worse – but only among the 66 patients who needed steroids for oncologic reasons (pain, brain metastases, anorexia, cancer-associated dyspnea). Among the 27 patients who received steroids for cancer-unrelated reasons (autoimmune disease, chronic obstructive pulmonary disease, hypersensitivity pneumonitis), progression-free and overall survival were no different than for patients on prednisone 0-9 mg/day. Imbalances in PD-L1 tumor proportion scores among the groups analyzed did not clearly account for the differences in survival.

What this means in practice

The potential for great treatment outcomes with single-agent ICIs in a subset of advanced NSCLC patients, coupled with the lack of an air-tight biomarker for benefit, has changed the timing of discussions between oncologists and patients about stopping antineoplastic treatment. Since we cannot identify the patients for whom ICI use is futile, the default position has been lenient on using these expensive and potentially toxic therapies.

If verified in a multi-institutional setting, with larger numbers of NSCLC patients receiving steroids for cancer-unrelated reasons, the observations of Dr. Ricciuti and colleagues could help clinicians confidently identify the time to focus discussions on supportive care only. In patients with short survival and strong rationale for maximizing supportive care, analyses like this one could help us deliver more appropriate treatment, instead of more treatment, thereby furthering the goals of personalized cancer patient management.
 

Dr. Lyss has been a community-based medical oncologist and clinical researcher for more than 35 years, practicing in St. Louis. His clinical and research interests are in the prevention, diagnosis, and treatment of breast and lung cancers and in expanding access to clinical trials to medically underserved populations.

The oral BRAF(V600E) kinase inhibitor vemurafenib (Zelboraf) has durable activity in non–small cell lung cancer (NSCLC) harboring BRAF V600 mutations and possibly provides greater benefit for treatment-naive patients, found the phase 2, open-label, single-arm VE-BASKET trial.

“Targetable oncogenic drivers in NSCLC with robust clinical validation include EGFR mutations and ALK and ROS1 fusions, but identifying other targetable, clinically important subgroups of NSCLC is a high priority,” wrote the investigators, who were led by Vivek Subbiah, MD, of the University of Texas MD Anderson Cancer Center, Houston. Roughly 1%-4% of NSCLC patients have tumors harboring a BRAF V600 mutation, they noted.

Analyses were based on 62 patients with BRAF V600–mutant NSCLC enrolled in the trial’s NSCLC cohort or all-comers cohort. All received vemurafenib (960 mg twice daily) until disease progression or unacceptable toxicity.

Thirteen percent of the patients had not received any previous systemic therapy. Among those previously treated, the median number of systemic regimens received was two.

Results reported in JCO Precicion Oncology showed that the median treatment duration was 6.0 months for all patients (12.0 months for previously untreated patients and 5.7 months for previously treated patients).

The objective response rate, the trial’s primary endpoint, was 37.1% overall; it was similar in the previously untreated group and the previously treated group (37.5% and 37.0%, respectively). The clinical benefit rate was 48.4% overall, with a larger differential according to previous treatment at 62.5% and 46.3%.

Median progression-free survival was 6.5 months in all patients (12.9 months in those previously untreated and 6.1 months in those previously treated), and median overall survival was 15.4 months in all patients (not estimable in those previously untreated, but 15.4 months in those previously treated).

The most common adverse events of any grade were nausea (seen in 40% of patients), hyperkeratosis (34%), and decreased appetite (32%). The most common grade 3 or worse adverse event was anemia (10%). The safety profile generally resembled that previously observed among patients with melanoma, with no new signals.

“Vemurafenib showed promising activity in patients with NSCLC harboring BRAF V600 mutations,” Dr. Subbiah and colleagues concluded. “The prolonged [overall survival] … in the NSCLC population represents promising durability of effect with single-agent BRAF inhibition.”

“The apparent increase in median [progression-free survival] in previously untreated patients compared with previously treated patients warrants additional investigation of earlier treatment in this patient population,” they maintained.

Dr. Subbiah disclosed having a consulting or advisory role with or receiving research funding from numerous pharmaceutical companies. The study was sponsored by Hoffmann-La Roche.

SOURCE: Subbiah V et al. JCO Precis Oncol. 2019 June 27. doi: 10.1200/PO.18.00266.

The oral BRAF(V600E) kinase inhibitor vemurafenib (Zelboraf) has durable activity in non–small cell lung cancer (NSCLC) harboring BRAF V600 mutations and possibly provides greater benefit for treatment-naive patients, found the phase 2, open-label, single-arm VE-BASKET trial.

“Targetable oncogenic drivers in NSCLC with robust clinical validation include EGFR mutations and ALK and ROS1 fusions, but identifying other targetable, clinically important subgroups of NSCLC is a high priority,” wrote the investigators, who were led by Vivek Subbiah, MD, of the University of Texas MD Anderson Cancer Center, Houston. Roughly 1%-4% of NSCLC patients have tumors harboring a BRAF V600 mutation, they noted.

Analyses were based on 62 patients with BRAF V600–mutant NSCLC enrolled in the trial’s NSCLC cohort or all-comers cohort. All received vemurafenib (960 mg twice daily) until disease progression or unacceptable toxicity.

Thirteen percent of the patients had not received any previous systemic therapy. Among those previously treated, the median number of systemic regimens received was two.

Results reported in JCO Precicion Oncology showed that the median treatment duration was 6.0 months for all patients (12.0 months for previously untreated patients and 5.7 months for previously treated patients).

The objective response rate, the trial’s primary endpoint, was 37.1% overall; it was similar in the previously untreated group and the previously treated group (37.5% and 37.0%, respectively). The clinical benefit rate was 48.4% overall, with a larger differential according to previous treatment at 62.5% and 46.3%.

Median progression-free survival was 6.5 months in all patients (12.9 months in those previously untreated and 6.1 months in those previously treated), and median overall survival was 15.4 months in all patients (not estimable in those previously untreated, but 15.4 months in those previously treated).

The most common adverse events of any grade were nausea (seen in 40% of patients), hyperkeratosis (34%), and decreased appetite (32%). The most common grade 3 or worse adverse event was anemia (10%). The safety profile generally resembled that previously observed among patients with melanoma, with no new signals.

“Vemurafenib showed promising activity in patients with NSCLC harboring BRAF V600 mutations,” Dr. Subbiah and colleagues concluded. “The prolonged [overall survival] … in the NSCLC population represents promising durability of effect with single-agent BRAF inhibition.”

“The apparent increase in median [progression-free survival] in previously untreated patients compared with previously treated patients warrants additional investigation of earlier treatment in this patient population,” they maintained.

Dr. Subbiah disclosed having a consulting or advisory role with or receiving research funding from numerous pharmaceutical companies. The study was sponsored by Hoffmann-La Roche.

SOURCE: Subbiah V et al. JCO Precis Oncol. 2019 June 27. doi: 10.1200/PO.18.00266.

The oral BRAF(V600E) kinase inhibitor vemurafenib (Zelboraf) has durable activity in non–small cell lung cancer (NSCLC) harboring BRAF V600 mutations and possibly provides greater benefit for treatment-naive patients, found the phase 2, open-label, single-arm VE-BASKET trial.

“Targetable oncogenic drivers in NSCLC with robust clinical validation include EGFR mutations and ALK and ROS1 fusions, but identifying other targetable, clinically important subgroups of NSCLC is a high priority,” wrote the investigators, who were led by Vivek Subbiah, MD, of the University of Texas MD Anderson Cancer Center, Houston. Roughly 1%-4% of NSCLC patients have tumors harboring a BRAF V600 mutation, they noted.

Analyses were based on 62 patients with BRAF V600–mutant NSCLC enrolled in the trial’s NSCLC cohort or all-comers cohort. All received vemurafenib (960 mg twice daily) until disease progression or unacceptable toxicity.

Thirteen percent of the patients had not received any previous systemic therapy. Among those previously treated, the median number of systemic regimens received was two.

Results reported in JCO Precicion Oncology showed that the median treatment duration was 6.0 months for all patients (12.0 months for previously untreated patients and 5.7 months for previously treated patients).

The objective response rate, the trial’s primary endpoint, was 37.1% overall; it was similar in the previously untreated group and the previously treated group (37.5% and 37.0%, respectively). The clinical benefit rate was 48.4% overall, with a larger differential according to previous treatment at 62.5% and 46.3%.

Median progression-free survival was 6.5 months in all patients (12.9 months in those previously untreated and 6.1 months in those previously treated), and median overall survival was 15.4 months in all patients (not estimable in those previously untreated, but 15.4 months in those previously treated).

The most common adverse events of any grade were nausea (seen in 40% of patients), hyperkeratosis (34%), and decreased appetite (32%). The most common grade 3 or worse adverse event was anemia (10%). The safety profile generally resembled that previously observed among patients with melanoma, with no new signals.

“Vemurafenib showed promising activity in patients with NSCLC harboring BRAF V600 mutations,” Dr. Subbiah and colleagues concluded. “The prolonged [overall survival] … in the NSCLC population represents promising durability of effect with single-agent BRAF inhibition.”

“The apparent increase in median [progression-free survival] in previously untreated patients compared with previously treated patients warrants additional investigation of earlier treatment in this patient population,” they maintained.

Dr. Subbiah disclosed having a consulting or advisory role with or receiving research funding from numerous pharmaceutical companies. The study was sponsored by Hoffmann-La Roche.

SOURCE: Subbiah V et al. JCO Precis Oncol. 2019 June 27. doi: 10.1200/PO.18.00266.

Testing for targetable alterations in a panel of genes is moderately more cost-effective than testing for single genetic markers in patients with advanced non–small cell lung cancer (NSCLC), finds a retrospective cohort study.

“Targeted therapies are now a therapeutic cornerstone for patients with [advanced NSCLC], but the best diagnostic approach for identifying those who are eligible for treatment remains uncertain,” noted the investigators, led by Lotte Steuten, PhD, Hutchinson Institute for Cancer Outcomes Research, Fred Hutchinson Cancer Research Center, Seattle.

Using the Flatiron Health database, the investigators identified 5,688 patients with stage IIIB or IV NSCLC who were tested for targetable genetic alterations. Overall, 15.4% of the patients had multigene panel sequencing (MGPS) entailing evaluation of at least 30 genes, while the rest had single-marker genetic testing (SMGT) entailing evaluation of markers for epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) or a smaller panel of variants.

Study results, reported in JCO Clinical Cancer Informatics, showed that 22% of the entire study cohort tested positive for EGFR mutations (18.5% with MGPS, 17.3% with SMGT) or ALK mutations (3.59% with MGPS, 3.78% with SMGT). In addition, 8% of those in the MGPS-tested group were found to have BRAF, RET, ROS1, HER2, or MET mutations.

The proportion of patients receiving treatments targeted to the specific mutations was 21% in the MGPS-tested group and 19% in the SMGT-tested group. The patients tested with MGPS had an expected survival that was 0.06 life-years longer (1.20 vs. 1.14) with lifetime total costs that were $8,814 higher per patient ($67,110 vs. $58,297).

Compared with SMGT, MGPS had an incremental cost-effectiveness ratio of $148,478 per life-year gained. This value can be characterized as moderate, given commonly cited threshold values in the United States that range from $50,000 to $200,000 per life-year gained, according to the investigators.

In sensitivity analyses, the expected incremental cost-effectiveness fell (improved) to $110,000 per life-year gained in a scenario in which all patients with an actionable mutation received a targeted treatment.

“Our cost-effectiveness analysis of MGPS versus SMGT provides evidence for health insurers who must consider both value and budget impact when weighing coverage policies for MGPS,” Dr. Steuten and colleagues wrote, noting that such evaluations are limited at present by reliance on retrospective data.

“To reduce decision uncertainty regarding insurance coverage of MGPS, our study highlights the need for prospective studies directly comparing the management of [advanced NSCLC] with MGPS versus SMGT that include both clinical and economic end points,” they concluded. “As this analysis represents a snapshot in time, the model developed should be updated as new clinical or cost information becomes available.”

Dr. Steuten disclosed having a consulting or advisory role with Agendia and Roche (immediate family member), and receiving research funding from Thermo Fisher Scientific, EMD Serono (institutional), Nohla Therapeutics (institutional), and the Personalized Medicine Coalition (institutional), which funded the study.

SOURCE: Steuten L et al. JCO Clin Cancer Inform. 2019 June 3. doi: 10.1200/CCI.19.00002.

Testing for targetable alterations in a panel of genes is moderately more cost-effective than testing for single genetic markers in patients with advanced non–small cell lung cancer (NSCLC), finds a retrospective cohort study.

“Targeted therapies are now a therapeutic cornerstone for patients with [advanced NSCLC], but the best diagnostic approach for identifying those who are eligible for treatment remains uncertain,” noted the investigators, led by Lotte Steuten, PhD, Hutchinson Institute for Cancer Outcomes Research, Fred Hutchinson Cancer Research Center, Seattle.

Using the Flatiron Health database, the investigators identified 5,688 patients with stage IIIB or IV NSCLC who were tested for targetable genetic alterations. Overall, 15.4% of the patients had multigene panel sequencing (MGPS) entailing evaluation of at least 30 genes, while the rest had single-marker genetic testing (SMGT) entailing evaluation of markers for epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) or a smaller panel of variants.

Study results, reported in JCO Clinical Cancer Informatics, showed that 22% of the entire study cohort tested positive for EGFR mutations (18.5% with MGPS, 17.3% with SMGT) or ALK mutations (3.59% with MGPS, 3.78% with SMGT). In addition, 8% of those in the MGPS-tested group were found to have BRAF, RET, ROS1, HER2, or MET mutations.

The proportion of patients receiving treatments targeted to the specific mutations was 21% in the MGPS-tested group and 19% in the SMGT-tested group. The patients tested with MGPS had an expected survival that was 0.06 life-years longer (1.20 vs. 1.14) with lifetime total costs that were $8,814 higher per patient ($67,110 vs. $58,297).

Compared with SMGT, MGPS had an incremental cost-effectiveness ratio of $148,478 per life-year gained. This value can be characterized as moderate, given commonly cited threshold values in the United States that range from $50,000 to $200,000 per life-year gained, according to the investigators.

In sensitivity analyses, the expected incremental cost-effectiveness fell (improved) to $110,000 per life-year gained in a scenario in which all patients with an actionable mutation received a targeted treatment.

“Our cost-effectiveness analysis of MGPS versus SMGT provides evidence for health insurers who must consider both value and budget impact when weighing coverage policies for MGPS,” Dr. Steuten and colleagues wrote, noting that such evaluations are limited at present by reliance on retrospective data.

“To reduce decision uncertainty regarding insurance coverage of MGPS, our study highlights the need for prospective studies directly comparing the management of [advanced NSCLC] with MGPS versus SMGT that include both clinical and economic end points,” they concluded. “As this analysis represents a snapshot in time, the model developed should be updated as new clinical or cost information becomes available.”

Dr. Steuten disclosed having a consulting or advisory role with Agendia and Roche (immediate family member), and receiving research funding from Thermo Fisher Scientific, EMD Serono (institutional), Nohla Therapeutics (institutional), and the Personalized Medicine Coalition (institutional), which funded the study.

SOURCE: Steuten L et al. JCO Clin Cancer Inform. 2019 June 3. doi: 10.1200/CCI.19.00002.

Testing for targetable alterations in a panel of genes is moderately more cost-effective than testing for single genetic markers in patients with advanced non–small cell lung cancer (NSCLC), finds a retrospective cohort study.

“Targeted therapies are now a therapeutic cornerstone for patients with [advanced NSCLC], but the best diagnostic approach for identifying those who are eligible for treatment remains uncertain,” noted the investigators, led by Lotte Steuten, PhD, Hutchinson Institute for Cancer Outcomes Research, Fred Hutchinson Cancer Research Center, Seattle.

Using the Flatiron Health database, the investigators identified 5,688 patients with stage IIIB or IV NSCLC who were tested for targetable genetic alterations. Overall, 15.4% of the patients had multigene panel sequencing (MGPS) entailing evaluation of at least 30 genes, while the rest had single-marker genetic testing (SMGT) entailing evaluation of markers for epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) or a smaller panel of variants.

Study results, reported in JCO Clinical Cancer Informatics, showed that 22% of the entire study cohort tested positive for EGFR mutations (18.5% with MGPS, 17.3% with SMGT) or ALK mutations (3.59% with MGPS, 3.78% with SMGT). In addition, 8% of those in the MGPS-tested group were found to have BRAF, RET, ROS1, HER2, or MET mutations.

The proportion of patients receiving treatments targeted to the specific mutations was 21% in the MGPS-tested group and 19% in the SMGT-tested group. The patients tested with MGPS had an expected survival that was 0.06 life-years longer (1.20 vs. 1.14) with lifetime total costs that were $8,814 higher per patient ($67,110 vs. $58,297).

Compared with SMGT, MGPS had an incremental cost-effectiveness ratio of $148,478 per life-year gained. This value can be characterized as moderate, given commonly cited threshold values in the United States that range from $50,000 to $200,000 per life-year gained, according to the investigators.

In sensitivity analyses, the expected incremental cost-effectiveness fell (improved) to $110,000 per life-year gained in a scenario in which all patients with an actionable mutation received a targeted treatment.

“Our cost-effectiveness analysis of MGPS versus SMGT provides evidence for health insurers who must consider both value and budget impact when weighing coverage policies for MGPS,” Dr. Steuten and colleagues wrote, noting that such evaluations are limited at present by reliance on retrospective data.

“To reduce decision uncertainty regarding insurance coverage of MGPS, our study highlights the need for prospective studies directly comparing the management of [advanced NSCLC] with MGPS versus SMGT that include both clinical and economic end points,” they concluded. “As this analysis represents a snapshot in time, the model developed should be updated as new clinical or cost information becomes available.”

Dr. Steuten disclosed having a consulting or advisory role with Agendia and Roche (immediate family member), and receiving research funding from Thermo Fisher Scientific, EMD Serono (institutional), Nohla Therapeutics (institutional), and the Personalized Medicine Coalition (institutional), which funded the study.

SOURCE: Steuten L et al. JCO Clin Cancer Inform. 2019 June 3. doi: 10.1200/CCI.19.00002.

The Food and Drug Administration has approved bevacizumab-bvzr (Zirabev) – a biosimilar to bevacizumab (Avastin) – for the treatment of five cancers: metastatic colorectal cancer (mCRC); unresectable, locally advanced, recurrent or metastatic non-squamous non–small cell lung cancer (NSCLC); recurrent glioblastoma; metastatic renal cell carcinoma (RCC); and persistent, recurrent or metastatic cervical cancer.

Approval was based on “review of a comprehensive data package which demonstrated biosimilarity of [bevacizumab-bvzr] to the reference product,” Pfizer said in a statement announcing the approval.

Bevacizumab-bvzr is the second bevacizumab biosimilar to be approved, following approval of Amgen’s bevacizumab-awwb (Mvasi) in 2017.

Warnings and precautions with the biosimilars, as with bevacizumab, include serious and sometimes fatal gastrointestinal perforation, surgery and wound healing complications, and sometimes serious and fatal hemorrhage.

The most common adverse events observed in bevacizumab patients are epistaxis, headache, hypertension, rhinitis, proteinuria, taste alteration, dry skin, rectal hemorrhage, lacrimation disorder, back pain, and exfoliative dermatitis.

Specific indications for the biosimilar are as follows:

Metastatic colorectal cancer

Bevacizumab-bvzr, in combination with intravenous fluorouracil-based chemotherapy, is indicated for the first- or second-line treatment of patients with mCRC.

Bevacizumab-bvzr, in combination with fluoropyrimidine-irinotecan or fluoropyrimidine-oxaliplatin–based chemotherapy, is indicated for the second-line treatment of patients with mCRC who have progressed on a first-line bevacizumab product–containing regimen.

Bevacizumab-bvzr is not indicated for adjuvant treatment of colon cancer.

First-line nonsquamous non–small cell lung cancer

Bevacizumab-bvzr, in combination with carboplatin and paclitaxel, is indicated for the first-line treatment of patients with unresectable, locally advanced, recurrent or metastatic NSCLC.

Recurrent glioblastoma

Bevacizumab-bvzr is indicated for the treatment of recurrent glioblastoma in adults.

Metastatic renal cell carcinoma

Bevacizumab-bvzr, in combination with interferon alfa, is indicated for the treatment of metastatic RCC.

Persistent, recurrent, or metastatic cervical cancer

Bevacizumab-bvzr, in combination with paclitaxel and cisplatin or paclitaxel and topotecan, is indicated for the treatment of patients with persistent, recurrent, or metastatic cervical cancer.

Complete prescribing information can be found on the FDA website.

The Food and Drug Administration has approved bevacizumab-bvzr (Zirabev) – a biosimilar to bevacizumab (Avastin) – for the treatment of five cancers: metastatic colorectal cancer (mCRC); unresectable, locally advanced, recurrent or metastatic non-squamous non–small cell lung cancer (NSCLC); recurrent glioblastoma; metastatic renal cell carcinoma (RCC); and persistent, recurrent or metastatic cervical cancer.

Approval was based on “review of a comprehensive data package which demonstrated biosimilarity of [bevacizumab-bvzr] to the reference product,” Pfizer said in a statement announcing the approval.

Bevacizumab-bvzr is the second bevacizumab biosimilar to be approved, following approval of Amgen’s bevacizumab-awwb (Mvasi) in 2017.

Warnings and precautions with the biosimilars, as with bevacizumab, include serious and sometimes fatal gastrointestinal perforation, surgery and wound healing complications, and sometimes serious and fatal hemorrhage.

The most common adverse events observed in bevacizumab patients are epistaxis, headache, hypertension, rhinitis, proteinuria, taste alteration, dry skin, rectal hemorrhage, lacrimation disorder, back pain, and exfoliative dermatitis.

Specific indications for the biosimilar are as follows:

Metastatic colorectal cancer

Bevacizumab-bvzr, in combination with intravenous fluorouracil-based chemotherapy, is indicated for the first- or second-line treatment of patients with mCRC.

Bevacizumab-bvzr, in combination with fluoropyrimidine-irinotecan or fluoropyrimidine-oxaliplatin–based chemotherapy, is indicated for the second-line treatment of patients with mCRC who have progressed on a first-line bevacizumab product–containing regimen.

Bevacizumab-bvzr is not indicated for adjuvant treatment of colon cancer.

First-line nonsquamous non–small cell lung cancer

Bevacizumab-bvzr, in combination with carboplatin and paclitaxel, is indicated for the first-line treatment of patients with unresectable, locally advanced, recurrent or metastatic NSCLC.

Recurrent glioblastoma

Bevacizumab-bvzr is indicated for the treatment of recurrent glioblastoma in adults.

Metastatic renal cell carcinoma

Bevacizumab-bvzr, in combination with interferon alfa, is indicated for the treatment of metastatic RCC.

Persistent, recurrent, or metastatic cervical cancer

Bevacizumab-bvzr, in combination with paclitaxel and cisplatin or paclitaxel and topotecan, is indicated for the treatment of patients with persistent, recurrent, or metastatic cervical cancer.

Complete prescribing information can be found on the FDA website.

The Food and Drug Administration has approved bevacizumab-bvzr (Zirabev) – a biosimilar to bevacizumab (Avastin) – for the treatment of five cancers: metastatic colorectal cancer (mCRC); unresectable, locally advanced, recurrent or metastatic non-squamous non–small cell lung cancer (NSCLC); recurrent glioblastoma; metastatic renal cell carcinoma (RCC); and persistent, recurrent or metastatic cervical cancer.

Approval was based on “review of a comprehensive data package which demonstrated biosimilarity of [bevacizumab-bvzr] to the reference product,” Pfizer said in a statement announcing the approval.

Bevacizumab-bvzr is the second bevacizumab biosimilar to be approved, following approval of Amgen’s bevacizumab-awwb (Mvasi) in 2017.

Warnings and precautions with the biosimilars, as with bevacizumab, include serious and sometimes fatal gastrointestinal perforation, surgery and wound healing complications, and sometimes serious and fatal hemorrhage.

The most common adverse events observed in bevacizumab patients are epistaxis, headache, hypertension, rhinitis, proteinuria, taste alteration, dry skin, rectal hemorrhage, lacrimation disorder, back pain, and exfoliative dermatitis.

Specific indications for the biosimilar are as follows:

Metastatic colorectal cancer

Bevacizumab-bvzr, in combination with intravenous fluorouracil-based chemotherapy, is indicated for the first- or second-line treatment of patients with mCRC.

Bevacizumab-bvzr, in combination with fluoropyrimidine-irinotecan or fluoropyrimidine-oxaliplatin–based chemotherapy, is indicated for the second-line treatment of patients with mCRC who have progressed on a first-line bevacizumab product–containing regimen.

Bevacizumab-bvzr is not indicated for adjuvant treatment of colon cancer.

First-line nonsquamous non–small cell lung cancer

Bevacizumab-bvzr, in combination with carboplatin and paclitaxel, is indicated for the first-line treatment of patients with unresectable, locally advanced, recurrent or metastatic NSCLC.

Recurrent glioblastoma

Bevacizumab-bvzr is indicated for the treatment of recurrent glioblastoma in adults.

Metastatic renal cell carcinoma

Bevacizumab-bvzr, in combination with interferon alfa, is indicated for the treatment of metastatic RCC.

Persistent, recurrent, or metastatic cervical cancer

Bevacizumab-bvzr, in combination with paclitaxel and cisplatin or paclitaxel and topotecan, is indicated for the treatment of patients with persistent, recurrent, or metastatic cervical cancer.

Complete prescribing information can be found on the FDA website.

Use of inhaled corticosteroids may lower the risk of lung cancer in patients with chronic obstructive pulmonary disease, and continued use may also reduce lung cancer risk, recent research from the European Respiratory Journal has shown.

“The appropriate use of [inhaled corticosteroids] ICS in [chronic obstructive pulmonary disease] COPD patients is often debated and not all patients might benefit from the use of ICS. The clinical benefits and risk of use in an individual patient must be weighed by the physician,” wrote Adam J.N. Raymakers, MSc, PhD, of the University of British Columbia’s Collaboration for Outcomes Research and Evaluation (CORE), Vancouver, B.C., and colleagues.

“This study, however, indicates that potential benefits may accrue from ICS use in COPD patients in terms of reduced lung cancer risk, and that sustained use may be associated with reduced risk of lung cancer.”

Dr. Raymakers and colleagues did an analysis of 39,676 patients with COPD (mean age, 70.7 years; 53% female) who received ICS between 1997 and 2007 and linked those patients to a registry of cancer patients in British Columbia. The linked databases included the Medical Services Plan (MSP) payment information file, Discharge Abstract Database (DAD), PharmaNet data file, and the British Columbia Cancer Registry (BCCR). The researchers determined a patient had COPD if he or she received three or more prescriptions related to COPD, while ICS exposure was analyzed in the context of a patient’s ICS exposure, cumulative duration, cumulative dose, and weighted cumulative duration and dose.

The analysis revealed 372,075 prescriptions for ICS were dispensed and 71.2% of the patients were “distinct users” of ICS, with patients filling a median of eight prescriptions at mean 5.2 years of follow-up. Fluticasone propionate was the most common ICS prescribed at a dose of 0.64 mg per day, and patients had median 60 days of ICS supplied per person.

Overall, there were 994 cases of lung cancer (2.5%), and exposure to ICS was linked to a 30% reduction in lung cancer risk (hazard ratio, 0.70; 95% confidence interval, 0.61-0.80), while recency-weighted duration of ICS exposure was linked to a 26% reduction in lung cancer risk (HR, 0.74; 95% CI, 0.66-0.87). There was a 43% reduced risk of lung cancer per gram of ICS when the data were measured by recency-weighted cumulative dosage.

In a multivariate analysis, ICS use was associated with a 30% reduction in risk of non–small cell lung cancer (HR, 0.70; 95% CI, 0.60-0.82), which the researchers said suggests ICS provides a protective effect for patients against lung cancer. “These results highlight the importance of properly identifying which patients might be at the highest risk of lung cancer, to enhance the therapeutic benefits of ICS in these COPD patients,” they wrote.

This study received funding from the Canadian Institutes of Health Research. The authors report no conflicts of interest.

SOURCE: Raymakers A, et al. Eur Respir J. 2019. doi: 10.1183/13993003.01257-2018.

Use of inhaled corticosteroids may lower the risk of lung cancer in patients with chronic obstructive pulmonary disease, and continued use may also reduce lung cancer risk, recent research from the European Respiratory Journal has shown.

“The appropriate use of [inhaled corticosteroids] ICS in [chronic obstructive pulmonary disease] COPD patients is often debated and not all patients might benefit from the use of ICS. The clinical benefits and risk of use in an individual patient must be weighed by the physician,” wrote Adam J.N. Raymakers, MSc, PhD, of the University of British Columbia’s Collaboration for Outcomes Research and Evaluation (CORE), Vancouver, B.C., and colleagues.

“This study, however, indicates that potential benefits may accrue from ICS use in COPD patients in terms of reduced lung cancer risk, and that sustained use may be associated with reduced risk of lung cancer.”

Dr. Raymakers and colleagues did an analysis of 39,676 patients with COPD (mean age, 70.7 years; 53% female) who received ICS between 1997 and 2007 and linked those patients to a registry of cancer patients in British Columbia. The linked databases included the Medical Services Plan (MSP) payment information file, Discharge Abstract Database (DAD), PharmaNet data file, and the British Columbia Cancer Registry (BCCR). The researchers determined a patient had COPD if he or she received three or more prescriptions related to COPD, while ICS exposure was analyzed in the context of a patient’s ICS exposure, cumulative duration, cumulative dose, and weighted cumulative duration and dose.

The analysis revealed 372,075 prescriptions for ICS were dispensed and 71.2% of the patients were “distinct users” of ICS, with patients filling a median of eight prescriptions at mean 5.2 years of follow-up. Fluticasone propionate was the most common ICS prescribed at a dose of 0.64 mg per day, and patients had median 60 days of ICS supplied per person.

Overall, there were 994 cases of lung cancer (2.5%), and exposure to ICS was linked to a 30% reduction in lung cancer risk (hazard ratio, 0.70; 95% confidence interval, 0.61-0.80), while recency-weighted duration of ICS exposure was linked to a 26% reduction in lung cancer risk (HR, 0.74; 95% CI, 0.66-0.87). There was a 43% reduced risk of lung cancer per gram of ICS when the data were measured by recency-weighted cumulative dosage.

In a multivariate analysis, ICS use was associated with a 30% reduction in risk of non–small cell lung cancer (HR, 0.70; 95% CI, 0.60-0.82), which the researchers said suggests ICS provides a protective effect for patients against lung cancer. “These results highlight the importance of properly identifying which patients might be at the highest risk of lung cancer, to enhance the therapeutic benefits of ICS in these COPD patients,” they wrote.

This study received funding from the Canadian Institutes of Health Research. The authors report no conflicts of interest.

SOURCE: Raymakers A, et al. Eur Respir J. 2019. doi: 10.1183/13993003.01257-2018.

Use of inhaled corticosteroids may lower the risk of lung cancer in patients with chronic obstructive pulmonary disease, and continued use may also reduce lung cancer risk, recent research from the European Respiratory Journal has shown.

“The appropriate use of [inhaled corticosteroids] ICS in [chronic obstructive pulmonary disease] COPD patients is often debated and not all patients might benefit from the use of ICS. The clinical benefits and risk of use in an individual patient must be weighed by the physician,” wrote Adam J.N. Raymakers, MSc, PhD, of the University of British Columbia’s Collaboration for Outcomes Research and Evaluation (CORE), Vancouver, B.C., and colleagues.

“This study, however, indicates that potential benefits may accrue from ICS use in COPD patients in terms of reduced lung cancer risk, and that sustained use may be associated with reduced risk of lung cancer.”

Dr. Raymakers and colleagues did an analysis of 39,676 patients with COPD (mean age, 70.7 years; 53% female) who received ICS between 1997 and 2007 and linked those patients to a registry of cancer patients in British Columbia. The linked databases included the Medical Services Plan (MSP) payment information file, Discharge Abstract Database (DAD), PharmaNet data file, and the British Columbia Cancer Registry (BCCR). The researchers determined a patient had COPD if he or she received three or more prescriptions related to COPD, while ICS exposure was analyzed in the context of a patient’s ICS exposure, cumulative duration, cumulative dose, and weighted cumulative duration and dose.

The analysis revealed 372,075 prescriptions for ICS were dispensed and 71.2% of the patients were “distinct users” of ICS, with patients filling a median of eight prescriptions at mean 5.2 years of follow-up. Fluticasone propionate was the most common ICS prescribed at a dose of 0.64 mg per day, and patients had median 60 days of ICS supplied per person.

Overall, there were 994 cases of lung cancer (2.5%), and exposure to ICS was linked to a 30% reduction in lung cancer risk (hazard ratio, 0.70; 95% confidence interval, 0.61-0.80), while recency-weighted duration of ICS exposure was linked to a 26% reduction in lung cancer risk (HR, 0.74; 95% CI, 0.66-0.87). There was a 43% reduced risk of lung cancer per gram of ICS when the data were measured by recency-weighted cumulative dosage.

In a multivariate analysis, ICS use was associated with a 30% reduction in risk of non–small cell lung cancer (HR, 0.70; 95% CI, 0.60-0.82), which the researchers said suggests ICS provides a protective effect for patients against lung cancer. “These results highlight the importance of properly identifying which patients might be at the highest risk of lung cancer, to enhance the therapeutic benefits of ICS in these COPD patients,” they wrote.

This study received funding from the Canadian Institutes of Health Research. The authors report no conflicts of interest.

SOURCE: Raymakers A, et al. Eur Respir J. 2019. doi: 10.1183/13993003.01257-2018.