In the Journals

Pembrolizumab shows durable survival benefit in advanced non-small cell lung cancer

Pembrolizumab monotherapy continued to show a survival advantage over chemotherapy among certain patients with previously untreated, advanced non-small cell lung cancer, according to an updated analysis of the randomized, phase 3 KEYNOTE-024 trial.

The OS benefit with first-line pembrolizumab (Keytruda, Merck) endured at median follow-up of 25.2 months despite significant crossover from the control group.

“For the first time, we do see improvement of long-time survival in patients with metastatic NSCLC,” Martin Reck, MD, PhD, head of the department of thoracic oncology and its clinical trial department at Lung Clinic Grosshansdorf in Germany, told HemOnc Today. “There are multiple trials currently investigating the role of innovative biomarkers and the potential implementation of additional opportunities to increase the immunogenicity of the tumor.”

The KEYNOTE-024 trial is designed to evaluate the safety and efficacy of pembrolizumab vs. platinum-based chemotherapy as first-line treatment for patients with NSCLC who have a PD-L1 tumor proportion score of 50% or greater but do not have EGFR/ALK aberrations.

Researchers randomly assigned 305 patients to pembrolizumab (n = 154) 200 mg every 3 weeks for up to 2 years or chemotherapy (n = 151). The study design allowed patients in the chemotherapy group to cross over to pembrolizumab.

PFS served as the primary endpoint. OS served as a key secondary endpoint.

An independent data and safety committee recommended the trial be discontinued after an interim analysis — performed at median follow-up of 11.2 months — showed significant improvements in PFS (HR = 0.5; 95% CI, 0.37-0.68) and OS (HR = 0.6; 95% CI, 0.41-0.89) with pembrolizumab.

The updated OS and tolerability results, after median follow-up of 25.2 months, included analyses adjusted for possible bias introduced by treatment crossover.

Seventy-three patients in the pembrolizumab group and 96 patients in the chemotherapy group died by data cutoff July 10, 2017.

Results showed median OS of 30 months (95% CI, 18.3-not reached) with pembrolizumab and 14.2 months (95% CI, 9.8-19) with chemotherapy (HR = 0.63; 95% CI, 0.47-0.86).

In an analysis adjusted for the crossover of 82 patients from chemotherapy to pembrolizumab, researchers observed an HR for OS with pembrolizumab vs. chemotherapy of 0.49 (95% CI, 0.34-0.69).

Using the Kaplan-Meier model, researchers estimated OS after 12 months of 70.3% (95% CI, 62.3-76.9) in the pembrolizumab group and 54.8% (95% CI, 46.4-62.4) in the chemotherapy group. At 24 months, estimated OS was 51.5% (95% CI, 43-59.3) with pembrolizumab vs. 34.5% (95% CI, 26.7-43.4) with chemotherapy.

Treatment-related grade 3 to 5 adverse events occurred among 31.2% of patients in the pembrolizumab group and 53.3% in the chemotherapy group.

“Overall, the crossover-adjusted analyses complement the primary efficacy analysis and reinforce the potential to improve outcomes with early use of pembrolizumab as first-line treatment,” Reck and colleagues wrote. “Given the OS and PFS benefits observed in KEYNOTE-024, pembrolizumab remains the only checkpoint inhibitor approved in the first-line setting as monotherapy for patients PD-L1 TPS of 50% or greater.” – by John DeRosier

For more information:

Martin Reck, MD, PhD, can be reached at: m.reck@lungenclinic.de.

Disclosures: Reck reports consultant/advisory roles with AbbVie, AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Eli Lilly, Genentech, Merck Serono, MSD Oncology, Novartis and Pfizer. Please see the study for all other authors’ relevant financial disclosures.

Pembrolizumab monotherapy continued to show a survival advantage over chemotherapy among certain patients with previously untreated, advanced non-small cell lung cancer, according to an updated analysis of the randomized, phase 3 KEYNOTE-024 trial.

The OS benefit with first-line pembrolizumab (Keytruda, Merck) endured at median follow-up of 25.2 months despite significant crossover from the control group.

“For the first time, we do see improvement of long-time survival in patients with metastatic NSCLC,” Martin Reck, MD, PhD, head of the department of thoracic oncology and its clinical trial department at Lung Clinic Grosshansdorf in Germany, told HemOnc Today. “There are multiple trials currently investigating the role of innovative biomarkers and the potential implementation of additional opportunities to increase the immunogenicity of the tumor.”

The KEYNOTE-024 trial is designed to evaluate the safety and efficacy of pembrolizumab vs. platinum-based chemotherapy as first-line treatment for patients with NSCLC who have a PD-L1 tumor proportion score of 50% or greater but do not have EGFR/ALK aberrations.

Researchers randomly assigned 305 patients to pembrolizumab (n = 154) 200 mg every 3 weeks for up to 2 years or chemotherapy (n = 151). The study design allowed patients in the chemotherapy group to cross over to pembrolizumab.

PFS served as the primary endpoint. OS served as a key secondary endpoint.

An independent data and safety committee recommended the trial be discontinued after an interim analysis — performed at median follow-up of 11.2 months — showed significant improvements in PFS (HR = 0.5; 95% CI, 0.37-0.68) and OS (HR = 0.6; 95% CI, 0.41-0.89) with pembrolizumab.

The updated OS and tolerability results, after median follow-up of 25.2 months, included analyses adjusted for possible bias introduced by treatment crossover.

Seventy-three patients in the pembrolizumab group and 96 patients in the chemotherapy group died by data cutoff July 10, 2017.

Results showed median OS of 30 months (95% CI, 18.3-not reached) with pembrolizumab and 14.2 months (95% CI, 9.8-19) with chemotherapy (HR = 0.63; 95% CI, 0.47-0.86).

In an analysis adjusted for the crossover of 82 patients from chemotherapy to pembrolizumab, researchers observed an HR for OS with pembrolizumab vs. chemotherapy of 0.49 (95% CI, 0.34-0.69).

Using the Kaplan-Meier model, researchers estimated OS after 12 months of 70.3% (95% CI, 62.3-76.9) in the pembrolizumab group and 54.8% (95% CI, 46.4-62.4) in the chemotherapy group. At 24 months, estimated OS was 51.5% (95% CI, 43-59.3) with pembrolizumab vs. 34.5% (95% CI, 26.7-43.4) with chemotherapy.

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Treatment-related grade 3 to 5 adverse events occurred among 31.2% of patients in the pembrolizumab group and 53.3% in the chemotherapy group.

“Overall, the crossover-adjusted analyses complement the primary efficacy analysis and reinforce the potential to improve outcomes with early use of pembrolizumab as first-line treatment,” Reck and colleagues wrote. “Given the OS and PFS benefits observed in KEYNOTE-024, pembrolizumab remains the only checkpoint inhibitor approved in the first-line setting as monotherapy for patients PD-L1 TPS of 50% or greater.” – by John DeRosier

For more information:

Martin Reck, MD, PhD, can be reached at: m.reck@lungenclinic.de.

Disclosures: Reck reports consultant/advisory roles with AbbVie, AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Eli Lilly, Genentech, Merck Serono, MSD Oncology, Novartis and Pfizer. Please see the study for all other authors’ relevant financial disclosures.

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