Alan P. Lyss, MD

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.

In this edition of “How I will treat my next patient,” I take a look at two “chemo-free” neoadjuvant studies reported at the annual meeting of the American Society of Clinical Oncology. One summarizes the potential utility of immune checkpoint inhibitors (ICIs) in non–small cell lung cancer (NSCLC) patients who are – or can become – candidates for curative resection and the other highlights the potential utility of neoadjuvant trastuzumab emtansine (T-DM1) for HER2-positive breast cancer patients.

NEOSTAR in NSCLC

With the accumulation of comorbid conditions in an aging population, we all see NSCLC patients who are potential candidates for curative surgery, but for whom we have concerns about standard preoperative chemotherapy plus or minus radiation. At ASCO 2019, abstracts 8503 (atezolizumab, the LCMC3 trial) and 8504 (nivolumab plus or minus ipilimumab, NEOSTAR) addressed the neoadjuvant use of ICIs. I will focus on NEOSTAR, because the major pathologic response (mPR) rate – reduction in viable tumor cells to 10% or less – was higher with the combination of nivolumab plus ipilimumab in NEOSTAR than with single agent nivolumab or atezolizumab in the NEOSTAR or LCMC3 trials, respectively.

Briefly, 44 patients with stage I-IIIA NSCLC were randomized to nivolumab plus or minus ipilimumab. In total, 93% completed 6 weeks of neoadjuvant therapy and 89% were resected. The mPR rate was 33% with nivolumab plus ipilimumab (about twice as high as with nivolumab alone in NEOSTAR or atezolizumab in LCMC3).

Among resected patients, nivolumab plus ipilimumab had a 44% mPR rate and a pathologic complete response rate of 38%. Although RECIST (Response Evaluation Criteria in Solid Tumors) responses were more likely in patients who had an mPR, 11% of patients had radiographic “nodal immune flare” because of noncaseating granulomas in regional (or nonregional) nodes. Elevated baseline programmed death-ligand 1 was associated with a higher rate of mPR. Surgical complications seemed similar to expectations – 1 bronchopleural fistula and 8 air leaks among the 39 resected patients.
 

What this means in practice

Although the mPR endpoint has no validated association with survival and the studies were relatively small, neoadjuvant use of ICIs in patients for whom tolerance to standard chemotherapy plus or minus radiation might be problematic is attractive – especially in view of the reality of an approximately 50% relapse rate after surgical resection with standard therapy.

If I had a potential candidate for neoadjuvant ICI therapy – especially one with a high proportion of cells with PD-L1 or someone with an equivocal distant metastasis on a preoperative PET-CT – I would consider using an ICI as given in LCMC3 or NEOSTAR.

PREDIX in HER2-positive breast cancer

As Mark Pegram, MD, of Stanford (Calif.) University suggested in his discussion at the local/regional/adjuvant breast cancer session at ASCO 2019, the goal of HER2-targeted therapy was originally that it could replace – not supplement – the use of cytotoxic chemotherapy.

Abstracts 500 (the KRISTINE trial: neoadjuvant T-DM1 plus pertuzumab vs. docetaxel, carboplatin, and trastuzumab plus pertuzumab); 501 (the PREDIX study: T-DM1 vs. docetaxel plus trastuzumab plus pertuzumab [DTP] for six cycles); and 502 (HER2 heterogeneity as a predictor of response) addressed the potential for the antibody-drug conjugate to replace standard preoperative cytotoxic chemotherapy plus HER2-targeting.

In PREDIX, it was anticipated that toxicity would be lower with T-DM1 than with DTP – and it was, with better quality of life scores. The authors found a pathologic complete response rate of 45% among 98 participants with stage IIA-IIIA HER2-positive breast cancer, with higher rates among hormone receptor–negative than hormone receptor–positive patients, as expected.

PREDIX patients were allowed to switch from T-DM1 to DTP for progression, lack of clinical/radiographic response, or toxicity. More than twice as many patients switched from DTP to T-DM1 than vice versa for progression or lack of response.

What this means in practice

Although neither DTP nor T-DM1 are National Comprehensive Cancer Network guideline-endorsed neoadjuvant regimens at present, the KRISTINE and PREDIX trials and Abstract 502 advance the discussion about further personalizing therapy for HER2-amplified breast cancer with high HER2 copy number and lack of intratumor heterogeneity for HER2. They also raise questions about de-escalating therapy for patients with good prognosis and HER2-positive cancers, and the creative use of T-DM1 in the neoadjuvant setting.

Neoadjuvant T-DM1 may not be standard of care yet, but watch this space.

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 two “chemo-free” neoadjuvant studies reported at the annual meeting of the American Society of Clinical Oncology. One summarizes the potential utility of immune checkpoint inhibitors (ICIs) in non–small cell lung cancer (NSCLC) patients who are – or can become – candidates for curative resection and the other highlights the potential utility of neoadjuvant trastuzumab emtansine (T-DM1) for HER2-positive breast cancer patients.

NEOSTAR in NSCLC

With the accumulation of comorbid conditions in an aging population, we all see NSCLC patients who are potential candidates for curative surgery, but for whom we have concerns about standard preoperative chemotherapy plus or minus radiation. At ASCO 2019, abstracts 8503 (atezolizumab, the LCMC3 trial) and 8504 (nivolumab plus or minus ipilimumab, NEOSTAR) addressed the neoadjuvant use of ICIs. I will focus on NEOSTAR, because the major pathologic response (mPR) rate – reduction in viable tumor cells to 10% or less – was higher with the combination of nivolumab plus ipilimumab in NEOSTAR than with single agent nivolumab or atezolizumab in the NEOSTAR or LCMC3 trials, respectively.

Briefly, 44 patients with stage I-IIIA NSCLC were randomized to nivolumab plus or minus ipilimumab. In total, 93% completed 6 weeks of neoadjuvant therapy and 89% were resected. The mPR rate was 33% with nivolumab plus ipilimumab (about twice as high as with nivolumab alone in NEOSTAR or atezolizumab in LCMC3).

Among resected patients, nivolumab plus ipilimumab had a 44% mPR rate and a pathologic complete response rate of 38%. Although RECIST (Response Evaluation Criteria in Solid Tumors) responses were more likely in patients who had an mPR, 11% of patients had radiographic “nodal immune flare” because of noncaseating granulomas in regional (or nonregional) nodes. Elevated baseline programmed death-ligand 1 was associated with a higher rate of mPR. Surgical complications seemed similar to expectations – 1 bronchopleural fistula and 8 air leaks among the 39 resected patients.
 

What this means in practice

Although the mPR endpoint has no validated association with survival and the studies were relatively small, neoadjuvant use of ICIs in patients for whom tolerance to standard chemotherapy plus or minus radiation might be problematic is attractive – especially in view of the reality of an approximately 50% relapse rate after surgical resection with standard therapy.

If I had a potential candidate for neoadjuvant ICI therapy – especially one with a high proportion of cells with PD-L1 or someone with an equivocal distant metastasis on a preoperative PET-CT – I would consider using an ICI as given in LCMC3 or NEOSTAR.

PREDIX in HER2-positive breast cancer

As Mark Pegram, MD, of Stanford (Calif.) University suggested in his discussion at the local/regional/adjuvant breast cancer session at ASCO 2019, the goal of HER2-targeted therapy was originally that it could replace – not supplement – the use of cytotoxic chemotherapy.

Abstracts 500 (the KRISTINE trial: neoadjuvant T-DM1 plus pertuzumab vs. docetaxel, carboplatin, and trastuzumab plus pertuzumab); 501 (the PREDIX study: T-DM1 vs. docetaxel plus trastuzumab plus pertuzumab [DTP] for six cycles); and 502 (HER2 heterogeneity as a predictor of response) addressed the potential for the antibody-drug conjugate to replace standard preoperative cytotoxic chemotherapy plus HER2-targeting.

In PREDIX, it was anticipated that toxicity would be lower with T-DM1 than with DTP – and it was, with better quality of life scores. The authors found a pathologic complete response rate of 45% among 98 participants with stage IIA-IIIA HER2-positive breast cancer, with higher rates among hormone receptor–negative than hormone receptor–positive patients, as expected.

PREDIX patients were allowed to switch from T-DM1 to DTP for progression, lack of clinical/radiographic response, or toxicity. More than twice as many patients switched from DTP to T-DM1 than vice versa for progression or lack of response.

What this means in practice

Although neither DTP nor T-DM1 are National Comprehensive Cancer Network guideline-endorsed neoadjuvant regimens at present, the KRISTINE and PREDIX trials and Abstract 502 advance the discussion about further personalizing therapy for HER2-amplified breast cancer with high HER2 copy number and lack of intratumor heterogeneity for HER2. They also raise questions about de-escalating therapy for patients with good prognosis and HER2-positive cancers, and the creative use of T-DM1 in the neoadjuvant setting.

Neoadjuvant T-DM1 may not be standard of care yet, but watch this space.

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 two “chemo-free” neoadjuvant studies reported at the annual meeting of the American Society of Clinical Oncology. One summarizes the potential utility of immune checkpoint inhibitors (ICIs) in non–small cell lung cancer (NSCLC) patients who are – or can become – candidates for curative resection and the other highlights the potential utility of neoadjuvant trastuzumab emtansine (T-DM1) for HER2-positive breast cancer patients.

NEOSTAR in NSCLC

With the accumulation of comorbid conditions in an aging population, we all see NSCLC patients who are potential candidates for curative surgery, but for whom we have concerns about standard preoperative chemotherapy plus or minus radiation. At ASCO 2019, abstracts 8503 (atezolizumab, the LCMC3 trial) and 8504 (nivolumab plus or minus ipilimumab, NEOSTAR) addressed the neoadjuvant use of ICIs. I will focus on NEOSTAR, because the major pathologic response (mPR) rate – reduction in viable tumor cells to 10% or less – was higher with the combination of nivolumab plus ipilimumab in NEOSTAR than with single agent nivolumab or atezolizumab in the NEOSTAR or LCMC3 trials, respectively.

Briefly, 44 patients with stage I-IIIA NSCLC were randomized to nivolumab plus or minus ipilimumab. In total, 93% completed 6 weeks of neoadjuvant therapy and 89% were resected. The mPR rate was 33% with nivolumab plus ipilimumab (about twice as high as with nivolumab alone in NEOSTAR or atezolizumab in LCMC3).

Among resected patients, nivolumab plus ipilimumab had a 44% mPR rate and a pathologic complete response rate of 38%. Although RECIST (Response Evaluation Criteria in Solid Tumors) responses were more likely in patients who had an mPR, 11% of patients had radiographic “nodal immune flare” because of noncaseating granulomas in regional (or nonregional) nodes. Elevated baseline programmed death-ligand 1 was associated with a higher rate of mPR. Surgical complications seemed similar to expectations – 1 bronchopleural fistula and 8 air leaks among the 39 resected patients.
 

What this means in practice

Although the mPR endpoint has no validated association with survival and the studies were relatively small, neoadjuvant use of ICIs in patients for whom tolerance to standard chemotherapy plus or minus radiation might be problematic is attractive – especially in view of the reality of an approximately 50% relapse rate after surgical resection with standard therapy.

If I had a potential candidate for neoadjuvant ICI therapy – especially one with a high proportion of cells with PD-L1 or someone with an equivocal distant metastasis on a preoperative PET-CT – I would consider using an ICI as given in LCMC3 or NEOSTAR.

PREDIX in HER2-positive breast cancer

As Mark Pegram, MD, of Stanford (Calif.) University suggested in his discussion at the local/regional/adjuvant breast cancer session at ASCO 2019, the goal of HER2-targeted therapy was originally that it could replace – not supplement – the use of cytotoxic chemotherapy.

Abstracts 500 (the KRISTINE trial: neoadjuvant T-DM1 plus pertuzumab vs. docetaxel, carboplatin, and trastuzumab plus pertuzumab); 501 (the PREDIX study: T-DM1 vs. docetaxel plus trastuzumab plus pertuzumab [DTP] for six cycles); and 502 (HER2 heterogeneity as a predictor of response) addressed the potential for the antibody-drug conjugate to replace standard preoperative cytotoxic chemotherapy plus HER2-targeting.

In PREDIX, it was anticipated that toxicity would be lower with T-DM1 than with DTP – and it was, with better quality of life scores. The authors found a pathologic complete response rate of 45% among 98 participants with stage IIA-IIIA HER2-positive breast cancer, with higher rates among hormone receptor–negative than hormone receptor–positive patients, as expected.

PREDIX patients were allowed to switch from T-DM1 to DTP for progression, lack of clinical/radiographic response, or toxicity. More than twice as many patients switched from DTP to T-DM1 than vice versa for progression or lack of response.

What this means in practice

Although neither DTP nor T-DM1 are National Comprehensive Cancer Network guideline-endorsed neoadjuvant regimens at present, the KRISTINE and PREDIX trials and Abstract 502 advance the discussion about further personalizing therapy for HER2-amplified breast cancer with high HER2 copy number and lack of intratumor heterogeneity for HER2. They also raise questions about de-escalating therapy for patients with good prognosis and HER2-positive cancers, and the creative use of T-DM1 in the neoadjuvant setting.

Neoadjuvant T-DM1 may not be standard of care yet, but watch this space.

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 two recent trials in non–small cell lung cancer (NSCLC). One summarizes a late analysis of a previously published randomized trial in stage IV NSCLC with three or fewer sites of metastasis – oligometastatic disease. The other reviews deidentified patient data to discern whether immune-targeted treatment might be valuable in particular subsets of NSCLC patients with EGFR mutations.

Local consolidative therapy

Daniel R. Gomez, MD, and colleagues published an updated analysis of progression-free survival (PFS) and an initial analysis of overall survival (OS) data in a randomized phase 2 trial in oligometastatic NSCLC. As originally published, patients were randomized to local consolidative treatment (LCT) versus standard maintenance therapy or observation (MT/O). Patients were required to have responding or stable disease after first-line systemic therapy prior to randomization.

Among the 49 patients who received LCT, there was a clear benefit of LCT (PFS of 14.2 months vs. 4.4 months for MT/O; P = .022; and median OS 41.2 months vs. 17.0 months; P = .017). The OS benefit was seen despite allowing crossover to LCT for patients who demonstrated disease progression in the MT/O arm.
 

What this means in practice

These data are exciting and move clinical research forward – if not, at this time, clinical practice. They support the ongoing clinical trials in NSCLC (NRG LU002) and breast cancer (NRG BR002) investigating the role of LCT in the oligometastatic setting.

For patients who are not candidates for (or choose not to participate in) these important phase 2R/3 trials, I believe that LCT should be discussed with all of the caveats that the authors appropriately mention, from the small number of patients because of the premature closure of the trial, to heterogeneous systemic regimens, to the lack of clarity on whether newer systemic therapies are better.

Immune checkpoint blockade

Historically, EGFR-mutated NSCLCs have not derived comparable benefit to EGFR-wild type (WT) tumors from checkpoint inhibitors. For that reason, in EGFR-mutated tumors, guidelines from the National Comprehensive Cancer Network (NCCN) suggest immune-targeted treatment should be used only on clinical trials or after receipt of EGFR-targeted tyrosine kinase inhibitors and cytotoxic chemotherapy. Several recent studies (IMpower and ATLANTIC), however, have suggested that selected EGFR-mutated patients can benefit from immune-targeted treatment.

Katherine Hastings, PhD, of Yale University, New Haven, Conn., and associates found, in a multi-institution clinical-molecular data review, that among the 44 of 171 EGFR-mutated tumors with L858R mutations, benefit from checkpoint inhibitors was comparable to WT tumors with regard to overall response rate and OS, but not PFS. Additionally, tumors with the EGFR T790M mutation demonstrated similar benefit from checkpoint inhibitors as in WT tumors, L858R-mutated tumors (but not exon 19 deleted tumors) had high tumor mutation burden, and PD-L1 expression did not influence outcome from immunotherapy.
 

What this means in practice

I agree with the modesty of the authors’ conclusion that these findings should not change clinical practice but rather should encourage further research into which patients with EGFR-mutant disease might benefit from immune-targeted therapy. For now, outside of a clinical trial, in EGFR-mutated patients, I will follow NCCN guidelines, using immune-targeted therapy off-study only with attentiveness to the particular immunotherapy regimens that have shown promise in the literature – and later, not earlier.

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 two recent trials in non–small cell lung cancer (NSCLC). One summarizes a late analysis of a previously published randomized trial in stage IV NSCLC with three or fewer sites of metastasis – oligometastatic disease. The other reviews deidentified patient data to discern whether immune-targeted treatment might be valuable in particular subsets of NSCLC patients with EGFR mutations.

Local consolidative therapy

Daniel R. Gomez, MD, and colleagues published an updated analysis of progression-free survival (PFS) and an initial analysis of overall survival (OS) data in a randomized phase 2 trial in oligometastatic NSCLC. As originally published, patients were randomized to local consolidative treatment (LCT) versus standard maintenance therapy or observation (MT/O). Patients were required to have responding or stable disease after first-line systemic therapy prior to randomization.

Among the 49 patients who received LCT, there was a clear benefit of LCT (PFS of 14.2 months vs. 4.4 months for MT/O; P = .022; and median OS 41.2 months vs. 17.0 months; P = .017). The OS benefit was seen despite allowing crossover to LCT for patients who demonstrated disease progression in the MT/O arm.
 

What this means in practice

These data are exciting and move clinical research forward – if not, at this time, clinical practice. They support the ongoing clinical trials in NSCLC (NRG LU002) and breast cancer (NRG BR002) investigating the role of LCT in the oligometastatic setting.

For patients who are not candidates for (or choose not to participate in) these important phase 2R/3 trials, I believe that LCT should be discussed with all of the caveats that the authors appropriately mention, from the small number of patients because of the premature closure of the trial, to heterogeneous systemic regimens, to the lack of clarity on whether newer systemic therapies are better.

Immune checkpoint blockade

Historically, EGFR-mutated NSCLCs have not derived comparable benefit to EGFR-wild type (WT) tumors from checkpoint inhibitors. For that reason, in EGFR-mutated tumors, guidelines from the National Comprehensive Cancer Network (NCCN) suggest immune-targeted treatment should be used only on clinical trials or after receipt of EGFR-targeted tyrosine kinase inhibitors and cytotoxic chemotherapy. Several recent studies (IMpower and ATLANTIC), however, have suggested that selected EGFR-mutated patients can benefit from immune-targeted treatment.

Katherine Hastings, PhD, of Yale University, New Haven, Conn., and associates found, in a multi-institution clinical-molecular data review, that among the 44 of 171 EGFR-mutated tumors with L858R mutations, benefit from checkpoint inhibitors was comparable to WT tumors with regard to overall response rate and OS, but not PFS. Additionally, tumors with the EGFR T790M mutation demonstrated similar benefit from checkpoint inhibitors as in WT tumors, L858R-mutated tumors (but not exon 19 deleted tumors) had high tumor mutation burden, and PD-L1 expression did not influence outcome from immunotherapy.
 

What this means in practice

I agree with the modesty of the authors’ conclusion that these findings should not change clinical practice but rather should encourage further research into which patients with EGFR-mutant disease might benefit from immune-targeted therapy. For now, outside of a clinical trial, in EGFR-mutated patients, I will follow NCCN guidelines, using immune-targeted therapy off-study only with attentiveness to the particular immunotherapy regimens that have shown promise in the literature – and later, not earlier.

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 two recent trials in non–small cell lung cancer (NSCLC). One summarizes a late analysis of a previously published randomized trial in stage IV NSCLC with three or fewer sites of metastasis – oligometastatic disease. The other reviews deidentified patient data to discern whether immune-targeted treatment might be valuable in particular subsets of NSCLC patients with EGFR mutations.

Local consolidative therapy

Daniel R. Gomez, MD, and colleagues published an updated analysis of progression-free survival (PFS) and an initial analysis of overall survival (OS) data in a randomized phase 2 trial in oligometastatic NSCLC. As originally published, patients were randomized to local consolidative treatment (LCT) versus standard maintenance therapy or observation (MT/O). Patients were required to have responding or stable disease after first-line systemic therapy prior to randomization.

Among the 49 patients who received LCT, there was a clear benefit of LCT (PFS of 14.2 months vs. 4.4 months for MT/O; P = .022; and median OS 41.2 months vs. 17.0 months; P = .017). The OS benefit was seen despite allowing crossover to LCT for patients who demonstrated disease progression in the MT/O arm.
 

What this means in practice

These data are exciting and move clinical research forward – if not, at this time, clinical practice. They support the ongoing clinical trials in NSCLC (NRG LU002) and breast cancer (NRG BR002) investigating the role of LCT in the oligometastatic setting.

For patients who are not candidates for (or choose not to participate in) these important phase 2R/3 trials, I believe that LCT should be discussed with all of the caveats that the authors appropriately mention, from the small number of patients because of the premature closure of the trial, to heterogeneous systemic regimens, to the lack of clarity on whether newer systemic therapies are better.

Immune checkpoint blockade

Historically, EGFR-mutated NSCLCs have not derived comparable benefit to EGFR-wild type (WT) tumors from checkpoint inhibitors. For that reason, in EGFR-mutated tumors, guidelines from the National Comprehensive Cancer Network (NCCN) suggest immune-targeted treatment should be used only on clinical trials or after receipt of EGFR-targeted tyrosine kinase inhibitors and cytotoxic chemotherapy. Several recent studies (IMpower and ATLANTIC), however, have suggested that selected EGFR-mutated patients can benefit from immune-targeted treatment.

Katherine Hastings, PhD, of Yale University, New Haven, Conn., and associates found, in a multi-institution clinical-molecular data review, that among the 44 of 171 EGFR-mutated tumors with L858R mutations, benefit from checkpoint inhibitors was comparable to WT tumors with regard to overall response rate and OS, but not PFS. Additionally, tumors with the EGFR T790M mutation demonstrated similar benefit from checkpoint inhibitors as in WT tumors, L858R-mutated tumors (but not exon 19 deleted tumors) had high tumor mutation burden, and PD-L1 expression did not influence outcome from immunotherapy.
 

What this means in practice

I agree with the modesty of the authors’ conclusion that these findings should not change clinical practice but rather should encourage further research into which patients with EGFR-mutant disease might benefit from immune-targeted therapy. For now, outside of a clinical trial, in EGFR-mutated patients, I will follow NCCN guidelines, using immune-targeted therapy off-study only with attentiveness to the particular immunotherapy regimens that have shown promise in the literature – and later, not earlier.

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 two recent trials – a late-breaking abstract presented at the annual meeting of the American Urological Association on the value of enzalutamide in hormone-sensitive metastatic prostate cancer (mHSPC) patients and a recent publication in JAMA Oncology about the potential for circulating tumor DNA (ctDNA) testing to inform our management of early stage colorectal cancer (CRC).

ARCHES trial

The ARCHES trial was reported as a late-breaking abstract at AUA 2019. ARCHES was a double-blind, placebo-controlled trial in 1,150 men with mHSPC. Patients were required to have been free from radiographic disease progression or a rising prostate-specific antigen (PSA) level for at least 3 months on androgen deprivation therapy (ADT) or at least 6 months after prior docetaxel chemotherapy.

Patients were randomly assigned to receive either ADT plus enzalutamide (an androgen receptor signaling inhibitor) or ADT plus placebo. The coprimary endpoints of the trial were radiographic progression-free survival (rPFS) and death within 24 weeks.

ADT plus enzalutamide had dramatically better PSA-related endpoints (as expected) and produced significantly better rPFS (median PFS, not reached versus 19.5 months; 61% relative prolongation of rPFS) than placebo plus ADT.

Overall survival data were unreported and may be confounded by all patients being offered enzalutamide at progression. Despite the known adverse effects of enzalutamide from prior studies, enzalutamide-related adverse effects in ARCHES were no worse than placebo (about 85% in both study arms). Formal quality-of-life analyses are yet to be reported.
 

What this means in practice

It is no surprise that enzalutamide, a potent drug in castration-resistant prostate cancer, would beat placebo. It joins docetaxel and abiraterone in helping to delay the time until castration-resistant disease develops – a meaningful goal. The authors commented that baseline PSA level did not predict benefit from enzalutamide – again, no surprise given that other published trials have suggested that baseline PSA is more likely prognostic than predictive.

It is always prudent to wait for a formal manuscript, but this abstract suggests that men with mHSPC have yet another option for treatment with modest toxicity and broad applicability in practice.
 

ctDNA in early colorectal cancer

In JAMA Oncology, Yuxuan Wang, MD, PhD, and colleagues summarized their experience with 58 patients with stages I-III colorectal cancer (CRC) who had curative-intent surgical resection at four Swedish hospitals.

The patients had levels of ctDNA monitored every 3 months post operatively. Prediction of the development of metastatic disease using ctDNA was compared to conventional surveillance testing (carcinoembryonic antigen [CEA] blood tests and computed tomographic scanning) per guidelines from the National Comprehensive Cancer Network.

Among the 45 patients with no elevation of ctDNA, there were no recurrences at median follow-up of 49 months. In contrast, 10 of 13 patients (77%) with elevated ctDNA levels during follow-up developed metastatic disease. CEA levels were less sensitive, detecting just 63% of recurrences.

Among the three patients with false positive ctDNA levels, all three fell to undetectable levels with continued follow-up. One of the 18 patients who received adjuvant post-operative chemotherapy had the ctDNA levels fall to undetectable with chemotherapy and that patient remained relapse-free at 37 months.

What this means in practice

The results of this study are remarkably concordant with recently published work in the Journal of Clinical Oncology by Emil Christensen, PhD, and colleagues, that involved patients with localized bladder cancer and illustrate the predictive value of ctDNA over traditional risk factors and conventional surveillance monitoring.

Monitoring ctDNA remains a promising research tool that should not be used for clinical decision making at the present time. However, its potential to help us personalize treatment selection, surveillance intensity, and to select patients who may be spared costly, toxic, and anxiety-provoking treatment and monitoring could be practice changing in the near future.

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 two recent trials – a late-breaking abstract presented at the annual meeting of the American Urological Association on the value of enzalutamide in hormone-sensitive metastatic prostate cancer (mHSPC) patients and a recent publication in JAMA Oncology about the potential for circulating tumor DNA (ctDNA) testing to inform our management of early stage colorectal cancer (CRC).

ARCHES trial

The ARCHES trial was reported as a late-breaking abstract at AUA 2019. ARCHES was a double-blind, placebo-controlled trial in 1,150 men with mHSPC. Patients were required to have been free from radiographic disease progression or a rising prostate-specific antigen (PSA) level for at least 3 months on androgen deprivation therapy (ADT) or at least 6 months after prior docetaxel chemotherapy.

Patients were randomly assigned to receive either ADT plus enzalutamide (an androgen receptor signaling inhibitor) or ADT plus placebo. The coprimary endpoints of the trial were radiographic progression-free survival (rPFS) and death within 24 weeks.

ADT plus enzalutamide had dramatically better PSA-related endpoints (as expected) and produced significantly better rPFS (median PFS, not reached versus 19.5 months; 61% relative prolongation of rPFS) than placebo plus ADT.

Overall survival data were unreported and may be confounded by all patients being offered enzalutamide at progression. Despite the known adverse effects of enzalutamide from prior studies, enzalutamide-related adverse effects in ARCHES were no worse than placebo (about 85% in both study arms). Formal quality-of-life analyses are yet to be reported.
 

What this means in practice

It is no surprise that enzalutamide, a potent drug in castration-resistant prostate cancer, would beat placebo. It joins docetaxel and abiraterone in helping to delay the time until castration-resistant disease develops – a meaningful goal. The authors commented that baseline PSA level did not predict benefit from enzalutamide – again, no surprise given that other published trials have suggested that baseline PSA is more likely prognostic than predictive.

It is always prudent to wait for a formal manuscript, but this abstract suggests that men with mHSPC have yet another option for treatment with modest toxicity and broad applicability in practice.
 

ctDNA in early colorectal cancer

In JAMA Oncology, Yuxuan Wang, MD, PhD, and colleagues summarized their experience with 58 patients with stages I-III colorectal cancer (CRC) who had curative-intent surgical resection at four Swedish hospitals.

The patients had levels of ctDNA monitored every 3 months post operatively. Prediction of the development of metastatic disease using ctDNA was compared to conventional surveillance testing (carcinoembryonic antigen [CEA] blood tests and computed tomographic scanning) per guidelines from the National Comprehensive Cancer Network.

Among the 45 patients with no elevation of ctDNA, there were no recurrences at median follow-up of 49 months. In contrast, 10 of 13 patients (77%) with elevated ctDNA levels during follow-up developed metastatic disease. CEA levels were less sensitive, detecting just 63% of recurrences.

Among the three patients with false positive ctDNA levels, all three fell to undetectable levels with continued follow-up. One of the 18 patients who received adjuvant post-operative chemotherapy had the ctDNA levels fall to undetectable with chemotherapy and that patient remained relapse-free at 37 months.

What this means in practice

The results of this study are remarkably concordant with recently published work in the Journal of Clinical Oncology by Emil Christensen, PhD, and colleagues, that involved patients with localized bladder cancer and illustrate the predictive value of ctDNA over traditional risk factors and conventional surveillance monitoring.

Monitoring ctDNA remains a promising research tool that should not be used for clinical decision making at the present time. However, its potential to help us personalize treatment selection, surveillance intensity, and to select patients who may be spared costly, toxic, and anxiety-provoking treatment and monitoring could be practice changing in the near future.

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 two recent trials – a late-breaking abstract presented at the annual meeting of the American Urological Association on the value of enzalutamide in hormone-sensitive metastatic prostate cancer (mHSPC) patients and a recent publication in JAMA Oncology about the potential for circulating tumor DNA (ctDNA) testing to inform our management of early stage colorectal cancer (CRC).

ARCHES trial

The ARCHES trial was reported as a late-breaking abstract at AUA 2019. ARCHES was a double-blind, placebo-controlled trial in 1,150 men with mHSPC. Patients were required to have been free from radiographic disease progression or a rising prostate-specific antigen (PSA) level for at least 3 months on androgen deprivation therapy (ADT) or at least 6 months after prior docetaxel chemotherapy.

Patients were randomly assigned to receive either ADT plus enzalutamide (an androgen receptor signaling inhibitor) or ADT plus placebo. The coprimary endpoints of the trial were radiographic progression-free survival (rPFS) and death within 24 weeks.

ADT plus enzalutamide had dramatically better PSA-related endpoints (as expected) and produced significantly better rPFS (median PFS, not reached versus 19.5 months; 61% relative prolongation of rPFS) than placebo plus ADT.

Overall survival data were unreported and may be confounded by all patients being offered enzalutamide at progression. Despite the known adverse effects of enzalutamide from prior studies, enzalutamide-related adverse effects in ARCHES were no worse than placebo (about 85% in both study arms). Formal quality-of-life analyses are yet to be reported.
 

What this means in practice

It is no surprise that enzalutamide, a potent drug in castration-resistant prostate cancer, would beat placebo. It joins docetaxel and abiraterone in helping to delay the time until castration-resistant disease develops – a meaningful goal. The authors commented that baseline PSA level did not predict benefit from enzalutamide – again, no surprise given that other published trials have suggested that baseline PSA is more likely prognostic than predictive.

It is always prudent to wait for a formal manuscript, but this abstract suggests that men with mHSPC have yet another option for treatment with modest toxicity and broad applicability in practice.
 

ctDNA in early colorectal cancer

In JAMA Oncology, Yuxuan Wang, MD, PhD, and colleagues summarized their experience with 58 patients with stages I-III colorectal cancer (CRC) who had curative-intent surgical resection at four Swedish hospitals.

The patients had levels of ctDNA monitored every 3 months post operatively. Prediction of the development of metastatic disease using ctDNA was compared to conventional surveillance testing (carcinoembryonic antigen [CEA] blood tests and computed tomographic scanning) per guidelines from the National Comprehensive Cancer Network.

Among the 45 patients with no elevation of ctDNA, there were no recurrences at median follow-up of 49 months. In contrast, 10 of 13 patients (77%) with elevated ctDNA levels during follow-up developed metastatic disease. CEA levels were less sensitive, detecting just 63% of recurrences.

Among the three patients with false positive ctDNA levels, all three fell to undetectable levels with continued follow-up. One of the 18 patients who received adjuvant post-operative chemotherapy had the ctDNA levels fall to undetectable with chemotherapy and that patient remained relapse-free at 37 months.

What this means in practice

The results of this study are remarkably concordant with recently published work in the Journal of Clinical Oncology by Emil Christensen, PhD, and colleagues, that involved patients with localized bladder cancer and illustrate the predictive value of ctDNA over traditional risk factors and conventional surveillance monitoring.

Monitoring ctDNA remains a promising research tool that should not be used for clinical decision making at the present time. However, its potential to help us personalize treatment selection, surveillance intensity, and to select patients who may be spared costly, toxic, and anxiety-provoking treatment and monitoring could be practice changing in the near future.

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 two recent trials – one offers potential in previously-treated cervical cancer patients with poor prognosis and the other confirms the role of R-CHOP as the standard of care in diffuse large B-cell lymphoma.

Pembrolizumab in KEYNOTE-158

In an international phase 2 “basket trial,” Hyun Cheol Chung, MD, PhD, and colleagues used pembrolizumab 200 mg every 3 weeks in 98 previously treated patients with advanced cervical cancer. Almost 84% of o the patients had PD-L1 positive tumors (greater than 1%). The authors said that viral induction of malignancy leads to antigen production and upregulation of PD-1. Therefore, advanced cervical cancer patients would likely express PD-L1 on tumor cells and respond to immune checkpoint inhibitor therapy.

In this interim report, there were 12 responses (all in PD-L1 positive patients), with three complete responses. Median response duration had not been reached at median follow-up of 10.2 months. Seven of 12 responses were ongoing at 12 months. There were grade 3-4 adverse events in 12.2% of patients and no treatment-related deaths.

The study – “Efficacy and Safety of Pembrolizumab in Previously Treated Advanced Cervical Cancer: Results From the Phase II KEYNOTE-158 Study” – was published in the Journal of Clinical Oncology (2019 April 3. doi: 10.1200/JCO.18.01265).


The encouraging results of pembrolizumab in this generally chemotherapy-refractory patient population were consistent with other small, early-phase studies investigating immune checkpoint inhibitors that led to the accelerated approval of pembrolizumab in previously treated PD-L1 advanced cervical cancer patients with progressive disease after chemotherapy.
 

What this means in practice

Although excitement should be tempered about an interim report of an organ-specific subset of a phase 2 international basket trial that was heavily populated by young PS 0-1 patients and generated an overall response rate of less than 15%, no conventional chemotherapy or biologic agent offers the potential of complete or prolonged response, and disease control rates of 30%.

Clinical trials should always be the first choice, but immune checkpoint inhibitors offer an attractive off-study option.

Among many single agents in National Comprehensive Cancer Network guidelines for recurrent advanced cervical cancer after first-line cisplatin-based chemotherapy, there is a reason why pembrolizumab is listed first. For patients with PD-L1 expressing tumors or MSI-H/dMMR tumors, I would use it.
 

Frontline therapy in DLBCL

In a large, randomized phase 3 trial, close to 500 stage III-IV patients with diffuse large B-cell lymphoma (DLBCL), including primary mediastinal B-cell lymphoma and intravascular large B-cell lymphoma, were assigned to receive either conventional R-CHOP chemotherapy or the more complex, more toxic DA-EPOCH-R regimen that appeared superior in single-institution studies and was feasible in multi-institutional phase 2 trials.

The study – “Dose-Adjusted EPOCH-R Compared With R-CHOP as Frontline Therapy for Diffuse Large B-Cell Lymphoma: Clinical Outcomes of the Phase III Intergroup Trial Alliance/CALGB 50303” – was published in the Journal of Clinical Oncology (2019 Apr 2. doi: 10.1200/JCO.18.01994).

In the study, progression-free survival and overall survival were no different for R-CHOP and DA-EPOCH-R, but – predictably – DA-EPOCH-R was more toxic and had more treatment discontinuations.

R-CHOP had better outcomes than expected. This suggests that patient-selection bias (more favorable histology, fewer high-risk subsets who required urgent therapy) may have been at work.

Further study of DA-EPOCH-R in higher IPI patients or in patients selected because of more adverse molecular features (DE phenotype, MYC+, double hit) is warranted given the poor outcomes with R-CHOP in high-risk patients, intriguing results in single institution trials of DA-EPOCH-R, and the underrepresentation of high-risk patients in the current study.
 

What this means in practice

Whether by virtue of the types of patients enrolled or because it is the best regimen in all DLBCL patients, R-CHOP remains the standard of care outside of a clinical trial.

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 two recent trials – one offers potential in previously-treated cervical cancer patients with poor prognosis and the other confirms the role of R-CHOP as the standard of care in diffuse large B-cell lymphoma.

Pembrolizumab in KEYNOTE-158

In an international phase 2 “basket trial,” Hyun Cheol Chung, MD, PhD, and colleagues used pembrolizumab 200 mg every 3 weeks in 98 previously treated patients with advanced cervical cancer. Almost 84% of o the patients had PD-L1 positive tumors (greater than 1%). The authors said that viral induction of malignancy leads to antigen production and upregulation of PD-1. Therefore, advanced cervical cancer patients would likely express PD-L1 on tumor cells and respond to immune checkpoint inhibitor therapy.

In this interim report, there were 12 responses (all in PD-L1 positive patients), with three complete responses. Median response duration had not been reached at median follow-up of 10.2 months. Seven of 12 responses were ongoing at 12 months. There were grade 3-4 adverse events in 12.2% of patients and no treatment-related deaths.

The study – “Efficacy and Safety of Pembrolizumab in Previously Treated Advanced Cervical Cancer: Results From the Phase II KEYNOTE-158 Study” – was published in the Journal of Clinical Oncology (2019 April 3. doi: 10.1200/JCO.18.01265).


The encouraging results of pembrolizumab in this generally chemotherapy-refractory patient population were consistent with other small, early-phase studies investigating immune checkpoint inhibitors that led to the accelerated approval of pembrolizumab in previously treated PD-L1 advanced cervical cancer patients with progressive disease after chemotherapy.
 

What this means in practice

Although excitement should be tempered about an interim report of an organ-specific subset of a phase 2 international basket trial that was heavily populated by young PS 0-1 patients and generated an overall response rate of less than 15%, no conventional chemotherapy or biologic agent offers the potential of complete or prolonged response, and disease control rates of 30%.

Clinical trials should always be the first choice, but immune checkpoint inhibitors offer an attractive off-study option.

Among many single agents in National Comprehensive Cancer Network guidelines for recurrent advanced cervical cancer after first-line cisplatin-based chemotherapy, there is a reason why pembrolizumab is listed first. For patients with PD-L1 expressing tumors or MSI-H/dMMR tumors, I would use it.
 

Frontline therapy in DLBCL

In a large, randomized phase 3 trial, close to 500 stage III-IV patients with diffuse large B-cell lymphoma (DLBCL), including primary mediastinal B-cell lymphoma and intravascular large B-cell lymphoma, were assigned to receive either conventional R-CHOP chemotherapy or the more complex, more toxic DA-EPOCH-R regimen that appeared superior in single-institution studies and was feasible in multi-institutional phase 2 trials.

The study – “Dose-Adjusted EPOCH-R Compared With R-CHOP as Frontline Therapy for Diffuse Large B-Cell Lymphoma: Clinical Outcomes of the Phase III Intergroup Trial Alliance/CALGB 50303” – was published in the Journal of Clinical Oncology (2019 Apr 2. doi: 10.1200/JCO.18.01994).

In the study, progression-free survival and overall survival were no different for R-CHOP and DA-EPOCH-R, but – predictably – DA-EPOCH-R was more toxic and had more treatment discontinuations.

R-CHOP had better outcomes than expected. This suggests that patient-selection bias (more favorable histology, fewer high-risk subsets who required urgent therapy) may have been at work.

Further study of DA-EPOCH-R in higher IPI patients or in patients selected because of more adverse molecular features (DE phenotype, MYC+, double hit) is warranted given the poor outcomes with R-CHOP in high-risk patients, intriguing results in single institution trials of DA-EPOCH-R, and the underrepresentation of high-risk patients in the current study.
 

What this means in practice

Whether by virtue of the types of patients enrolled or because it is the best regimen in all DLBCL patients, R-CHOP remains the standard of care outside of a clinical trial.

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 two recent trials – one offers potential in previously-treated cervical cancer patients with poor prognosis and the other confirms the role of R-CHOP as the standard of care in diffuse large B-cell lymphoma.

Pembrolizumab in KEYNOTE-158

In an international phase 2 “basket trial,” Hyun Cheol Chung, MD, PhD, and colleagues used pembrolizumab 200 mg every 3 weeks in 98 previously treated patients with advanced cervical cancer. Almost 84% of o the patients had PD-L1 positive tumors (greater than 1%). The authors said that viral induction of malignancy leads to antigen production and upregulation of PD-1. Therefore, advanced cervical cancer patients would likely express PD-L1 on tumor cells and respond to immune checkpoint inhibitor therapy.

In this interim report, there were 12 responses (all in PD-L1 positive patients), with three complete responses. Median response duration had not been reached at median follow-up of 10.2 months. Seven of 12 responses were ongoing at 12 months. There were grade 3-4 adverse events in 12.2% of patients and no treatment-related deaths.

The study – “Efficacy and Safety of Pembrolizumab in Previously Treated Advanced Cervical Cancer: Results From the Phase II KEYNOTE-158 Study” – was published in the Journal of Clinical Oncology (2019 April 3. doi: 10.1200/JCO.18.01265).


The encouraging results of pembrolizumab in this generally chemotherapy-refractory patient population were consistent with other small, early-phase studies investigating immune checkpoint inhibitors that led to the accelerated approval of pembrolizumab in previously treated PD-L1 advanced cervical cancer patients with progressive disease after chemotherapy.
 

What this means in practice

Although excitement should be tempered about an interim report of an organ-specific subset of a phase 2 international basket trial that was heavily populated by young PS 0-1 patients and generated an overall response rate of less than 15%, no conventional chemotherapy or biologic agent offers the potential of complete or prolonged response, and disease control rates of 30%.

Clinical trials should always be the first choice, but immune checkpoint inhibitors offer an attractive off-study option.

Among many single agents in National Comprehensive Cancer Network guidelines for recurrent advanced cervical cancer after first-line cisplatin-based chemotherapy, there is a reason why pembrolizumab is listed first. For patients with PD-L1 expressing tumors or MSI-H/dMMR tumors, I would use it.
 

Frontline therapy in DLBCL

In a large, randomized phase 3 trial, close to 500 stage III-IV patients with diffuse large B-cell lymphoma (DLBCL), including primary mediastinal B-cell lymphoma and intravascular large B-cell lymphoma, were assigned to receive either conventional R-CHOP chemotherapy or the more complex, more toxic DA-EPOCH-R regimen that appeared superior in single-institution studies and was feasible in multi-institutional phase 2 trials.

The study – “Dose-Adjusted EPOCH-R Compared With R-CHOP as Frontline Therapy for Diffuse Large B-Cell Lymphoma: Clinical Outcomes of the Phase III Intergroup Trial Alliance/CALGB 50303” – was published in the Journal of Clinical Oncology (2019 Apr 2. doi: 10.1200/JCO.18.01994).

In the study, progression-free survival and overall survival were no different for R-CHOP and DA-EPOCH-R, but – predictably – DA-EPOCH-R was more toxic and had more treatment discontinuations.

R-CHOP had better outcomes than expected. This suggests that patient-selection bias (more favorable histology, fewer high-risk subsets who required urgent therapy) may have been at work.

Further study of DA-EPOCH-R in higher IPI patients or in patients selected because of more adverse molecular features (DE phenotype, MYC+, double hit) is warranted given the poor outcomes with R-CHOP in high-risk patients, intriguing results in single institution trials of DA-EPOCH-R, and the underrepresentation of high-risk patients in the current study.
 

What this means in practice

Whether by virtue of the types of patients enrolled or because it is the best regimen in all DLBCL patients, R-CHOP remains the standard of care outside of a clinical trial.

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.

Welcome to the first edition of “How I will treat my next patient,” a regular column analyzing the practical clinical relevance of the latest literature. In this first column, I will take a look at two interesting studies – a combination hormonal treatment for metastatic ER-positive breast cancer and aspirin therapy for prevention of hepatocellular cancer.

Anastrozole plus fulvestrant

In a large SWOG trial for postmenopausal patients with stage IV, hormonally responsive breast cancer whose metastatic disease could be treated with frontline hormonal therapy, long-term survival analysis showed that the combination of anastrozole plus fulvestrant was superior to anastrozole alone, with essentially no increase in toxicity.

The study – “Overall Survival With Fulvestrant Plus Anastrozole in Metastatic Breast Cancer” – was published in the New England Journal of Medicine (2019;380:1226-34).

The overall survival difference was not only statistically and clinically significant, but impressively so among patients who had not received prior adjuvant hormonal therapy. That is despite the fact that 45% of patients who were assigned to initial treatment with anastrozole received single agent fulvestrant at first relapse.

What this means in practice

Because of the generally negative results of combined hormonal therapy in comparison with sequential use of the same agents and the potency of CDK4/6 inhibitors in combination with hormonal agents in the frontline setting, many oncologists have forgotten the initial publication of this regimen in 2012. In that study, the combination demonstrated improved progression-free survival over anastrozole alone, particularly in the subset of patients who presented with stage IV breast cancer as their initial presentation.

Although the benefits for CDK4/6 inhibitors as an addition to hormonal therapy are truly impressive, the practical aspects of utilizing the CDK4/6 inhibitors may be prohibitive for a small subset of our most vulnerable, medically underserved patients. Specifically, these are patients who are unable to return for frequent blood counts in the initial few months of therapy, patients with limited financial resources who cannot afford the out-of-pocket costs of an expensive oral medication and required laboratory testing, those with difficulty adhering to oral medication regimens, or those with constitutional neutropenia.

Not coincidentally, many of these patients are exactly the ones who present with stage IV disease as their initial manifestation of breast cancer. For such patients, the combination of anastrozole plus fulvestrant is an attractive alternative and may offer competitive survival benefits. This is not “yesterday’s therapy” in the era of CDK4/6 inhibitors, but rather represents a valuable option for treatment in at-risk populations.

When I see my next patient who presents with stage IV breast cancer, I will consider combined hormonal therapy among the various available treatment options.

Aspirin to prevent HCC

Investigators at Taichung (Taiwan) Veterans General Hospital recently analyzed 16 years of data from a cohort of more than 10,000 patients with chronic hepatitis B virus (HBV) infection and found statistically significantly fewer cases of hepatocellular cancer (HCC) in patients who took antiviral antinucleoside analogue therapy, statins, and aspirin.

The study – “Association of Daily Aspirin Therapy With Risk of Hepatocellular Carcinoma in Patients With Chronic Hepatitis B” – was published in JAMA Internal Medicine (doi: 10.1001/jamainternmed.2018.8342).

Although there were more impressive reductions in relative risk of HCC among statin and antinucleoside analogue users, the authors highlighted that HCC developed in 5.20% of the approximately 2,100 chronic aspirin users and in 7.87% of nonusers – a 29% relative reduction in risk in this cohort study. Toxicity, including upper GI bleeding, was low.

What this means in practice

This is a hypothesis-generating analysis at best. Although the authors highlight possible mechanisms by which aspirin use could lead to reduction in HCC among patients with chronic inflammatory conditions affecting the liver, the study produces more questions than it answers (dose, chronicity of use, duration of protection, biomarkers for benefit).

Owing to the simplicity and low cost of the intervention, it may be worth studying prospectively in chronic HBV-infected patients and other populations at risk for HCC, but the intervention should not be adopted at this point based on an international cohort study.

The practicality of conducting such a large, complicated, prospective study of a widely available medication that has widely publicized additional health benefits is an open question.

When I see my next patient with a high risk for HCC, I won’t prescribe aspirin for chemoprevention.

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.

Welcome to the first edition of “How I will treat my next patient,” a regular column analyzing the practical clinical relevance of the latest literature. In this first column, I will take a look at two interesting studies – a combination hormonal treatment for metastatic ER-positive breast cancer and aspirin therapy for prevention of hepatocellular cancer.

Anastrozole plus fulvestrant

In a large SWOG trial for postmenopausal patients with stage IV, hormonally responsive breast cancer whose metastatic disease could be treated with frontline hormonal therapy, long-term survival analysis showed that the combination of anastrozole plus fulvestrant was superior to anastrozole alone, with essentially no increase in toxicity.

The study – “Overall Survival With Fulvestrant Plus Anastrozole in Metastatic Breast Cancer” – was published in the New England Journal of Medicine (2019;380:1226-34).

The overall survival difference was not only statistically and clinically significant, but impressively so among patients who had not received prior adjuvant hormonal therapy. That is despite the fact that 45% of patients who were assigned to initial treatment with anastrozole received single agent fulvestrant at first relapse.

What this means in practice

Because of the generally negative results of combined hormonal therapy in comparison with sequential use of the same agents and the potency of CDK4/6 inhibitors in combination with hormonal agents in the frontline setting, many oncologists have forgotten the initial publication of this regimen in 2012. In that study, the combination demonstrated improved progression-free survival over anastrozole alone, particularly in the subset of patients who presented with stage IV breast cancer as their initial presentation.

Although the benefits for CDK4/6 inhibitors as an addition to hormonal therapy are truly impressive, the practical aspects of utilizing the CDK4/6 inhibitors may be prohibitive for a small subset of our most vulnerable, medically underserved patients. Specifically, these are patients who are unable to return for frequent blood counts in the initial few months of therapy, patients with limited financial resources who cannot afford the out-of-pocket costs of an expensive oral medication and required laboratory testing, those with difficulty adhering to oral medication regimens, or those with constitutional neutropenia.

Not coincidentally, many of these patients are exactly the ones who present with stage IV disease as their initial manifestation of breast cancer. For such patients, the combination of anastrozole plus fulvestrant is an attractive alternative and may offer competitive survival benefits. This is not “yesterday’s therapy” in the era of CDK4/6 inhibitors, but rather represents a valuable option for treatment in at-risk populations.

When I see my next patient who presents with stage IV breast cancer, I will consider combined hormonal therapy among the various available treatment options.

Aspirin to prevent HCC

Investigators at Taichung (Taiwan) Veterans General Hospital recently analyzed 16 years of data from a cohort of more than 10,000 patients with chronic hepatitis B virus (HBV) infection and found statistically significantly fewer cases of hepatocellular cancer (HCC) in patients who took antiviral antinucleoside analogue therapy, statins, and aspirin.

The study – “Association of Daily Aspirin Therapy With Risk of Hepatocellular Carcinoma in Patients With Chronic Hepatitis B” – was published in JAMA Internal Medicine (doi: 10.1001/jamainternmed.2018.8342).

Although there were more impressive reductions in relative risk of HCC among statin and antinucleoside analogue users, the authors highlighted that HCC developed in 5.20% of the approximately 2,100 chronic aspirin users and in 7.87% of nonusers – a 29% relative reduction in risk in this cohort study. Toxicity, including upper GI bleeding, was low.

What this means in practice

This is a hypothesis-generating analysis at best. Although the authors highlight possible mechanisms by which aspirin use could lead to reduction in HCC among patients with chronic inflammatory conditions affecting the liver, the study produces more questions than it answers (dose, chronicity of use, duration of protection, biomarkers for benefit).

Owing to the simplicity and low cost of the intervention, it may be worth studying prospectively in chronic HBV-infected patients and other populations at risk for HCC, but the intervention should not be adopted at this point based on an international cohort study.

The practicality of conducting such a large, complicated, prospective study of a widely available medication that has widely publicized additional health benefits is an open question.

When I see my next patient with a high risk for HCC, I won’t prescribe aspirin for chemoprevention.

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.

Welcome to the first edition of “How I will treat my next patient,” a regular column analyzing the practical clinical relevance of the latest literature. In this first column, I will take a look at two interesting studies – a combination hormonal treatment for metastatic ER-positive breast cancer and aspirin therapy for prevention of hepatocellular cancer.

Anastrozole plus fulvestrant

In a large SWOG trial for postmenopausal patients with stage IV, hormonally responsive breast cancer whose metastatic disease could be treated with frontline hormonal therapy, long-term survival analysis showed that the combination of anastrozole plus fulvestrant was superior to anastrozole alone, with essentially no increase in toxicity.

The study – “Overall Survival With Fulvestrant Plus Anastrozole in Metastatic Breast Cancer” – was published in the New England Journal of Medicine (2019;380:1226-34).

The overall survival difference was not only statistically and clinically significant, but impressively so among patients who had not received prior adjuvant hormonal therapy. That is despite the fact that 45% of patients who were assigned to initial treatment with anastrozole received single agent fulvestrant at first relapse.

What this means in practice

Because of the generally negative results of combined hormonal therapy in comparison with sequential use of the same agents and the potency of CDK4/6 inhibitors in combination with hormonal agents in the frontline setting, many oncologists have forgotten the initial publication of this regimen in 2012. In that study, the combination demonstrated improved progression-free survival over anastrozole alone, particularly in the subset of patients who presented with stage IV breast cancer as their initial presentation.

Although the benefits for CDK4/6 inhibitors as an addition to hormonal therapy are truly impressive, the practical aspects of utilizing the CDK4/6 inhibitors may be prohibitive for a small subset of our most vulnerable, medically underserved patients. Specifically, these are patients who are unable to return for frequent blood counts in the initial few months of therapy, patients with limited financial resources who cannot afford the out-of-pocket costs of an expensive oral medication and required laboratory testing, those with difficulty adhering to oral medication regimens, or those with constitutional neutropenia.

Not coincidentally, many of these patients are exactly the ones who present with stage IV disease as their initial manifestation of breast cancer. For such patients, the combination of anastrozole plus fulvestrant is an attractive alternative and may offer competitive survival benefits. This is not “yesterday’s therapy” in the era of CDK4/6 inhibitors, but rather represents a valuable option for treatment in at-risk populations.

When I see my next patient who presents with stage IV breast cancer, I will consider combined hormonal therapy among the various available treatment options.

Aspirin to prevent HCC

Investigators at Taichung (Taiwan) Veterans General Hospital recently analyzed 16 years of data from a cohort of more than 10,000 patients with chronic hepatitis B virus (HBV) infection and found statistically significantly fewer cases of hepatocellular cancer (HCC) in patients who took antiviral antinucleoside analogue therapy, statins, and aspirin.

The study – “Association of Daily Aspirin Therapy With Risk of Hepatocellular Carcinoma in Patients With Chronic Hepatitis B” – was published in JAMA Internal Medicine (doi: 10.1001/jamainternmed.2018.8342).

Although there were more impressive reductions in relative risk of HCC among statin and antinucleoside analogue users, the authors highlighted that HCC developed in 5.20% of the approximately 2,100 chronic aspirin users and in 7.87% of nonusers – a 29% relative reduction in risk in this cohort study. Toxicity, including upper GI bleeding, was low.

What this means in practice

This is a hypothesis-generating analysis at best. Although the authors highlight possible mechanisms by which aspirin use could lead to reduction in HCC among patients with chronic inflammatory conditions affecting the liver, the study produces more questions than it answers (dose, chronicity of use, duration of protection, biomarkers for benefit).

Owing to the simplicity and low cost of the intervention, it may be worth studying prospectively in chronic HBV-infected patients and other populations at risk for HCC, but the intervention should not be adopted at this point based on an international cohort study.

The practicality of conducting such a large, complicated, prospective study of a widely available medication that has widely publicized additional health benefits is an open question.

When I see my next patient with a high risk for HCC, I won’t prescribe aspirin for chemoprevention.

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.