Three-year survival update confirms efficacy of pembrolizumab in non-small cell lung cancer

BARCELONA — First-line pembrolizumab monotherapy conferred a durable long-term OS benefit compared with chemotherapy for patients with metastatic, PD-L1-expressing non-small cell lung cancer, according to 3-year survival results of the KEYNOTE-024 trial presented at International Association for the Study of Lung Cancer World Conference on Lung Cancer.

“Immunotherapy has completely changed the management of lung cancer. We’re changing lung cancer to a chronic disease with good quality of life,” Martin Reck, MD, PhD, head of the thoracic oncology service at Lung Clinic Grosshansdorf in Germany, said during a press conference. “What we have seen is that immunotherapy with pembrolizumab is a monotherapy opportunity for first-line treatment of patients with PD-L1 expression as well as in combination with chemotherapy for patients regardless of PD-L1 expression.”

The phase 3 KEYNOTE-024 trial evaluated the safety and efficacy of pembrolizumab vs. platinum-based chemotherapy as first-line treatment for patients with advanced NSCLC who have a PD-L1 tumor proportion score of 50% or greater but do not have targetable EGFR/ALK aberrations.

Reck and colleagues randomly assigned 305 participants in the trial to pembrolizumab (Keytruda, Merck) dosed at 200 mg every 3 weeks for up to 2 years (n = 154) or four to six cycles of platinum doublet chemotherapy (at the investigator’s discretion) plus optimal maintenance for those with nonsquamous disease (n = 151). The study design allowed eligible patients in the chemotherapy group who experienced disease progression to cross over to pembrolizumab.

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

Median follow-up at data cutoff of Feb. 15 was 44.4 months (range, 39.6-52.9).

By that time, 210 patients had died, including 97 in the pembrolizumab group and 113 in the chemotherapy group. Ninety-eight patients (64.9%) crossed over from chemotherapy to anti-PD-L1 therapy during or outside of the study interval.

Results showed median OS of 26.3 months (95% CI, 18.3-40.4) in the pembrolizumab group vs. 14.2 months (95% CI, 9.8-18.3) in the chemotherapy group (HR = 0.65; 95% CI, 0.5-0.86). The 36-month OS rate was 43.7% with pembrolizumab vs. 24.9% with chemotherapy.

Although mean duration of treatment was longer with pembrolizumab vs. chemotherapy (11.1 vs. 4.4 months), grade 3 to grade 5 treatment-related adverse events occurred less frequently with pembrolizumab (31.2% vs. 53.3%).

“Then we looked at immune-related adverse events, and the question was, what are we inducing when we treat patients for 2 years?” Reck said. “Interestingly, we haven’t seen a lot of changes in the frequencies of immune-mediated adverse events. Thirty-four patients do have immune-mediated adverse events but when we look at the kind of immune-mediated adverse events, they are the same as the ones we’ve seen.”

These include infusion reactions, gastrointestinal events and pulmonary toxicities, Reck added.

Thirty-eight patients in the pembrolizumab group finished 2 years (35 cycles) of therapy. Among these patients, 34 remained alive, 31 (81.6%) demonstrated an objective response (including three with complete response) and median duration of response was not reached (range, 4.2-46.7+). Five (13.2%) patients had treatment-related grade 3 to grade 4 adverse events, none of which resulted in death.

At data cutoff, 71% of patients with a duration of response of at least 2 years had stable disease without the need for additional treatment, Reck said.

Reck also presented data on 10 patients who progressed after 2 years of pembrolizumab and underwent a second course of the treatment; seven had an objective response and eight are alive.

“We are confirming the efficacy of pembrolizumab in this long-term analysis, with a consistent OS benefit, and we see this benefit despite the crossover of 65%,” Reck said. “We have also seen preliminary results that demonstrate the feasibility of a second course of pembrolizumab, and that response is achievable despite prior exposure to pembrolizumab.” – by Jennifer Byrne

Reference:

Reck M, et al. Abstract OA14.01. Presented at: International Association for the Study of Lung Cancer World Conference on Lung Cancer; Sept. 7-10, 2019; Barcelona.

Disclosures: Reck reports honoraria from and consultant/advisory or speakers’ bureau roles with AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Celgene, Eli Lilly, F. Hoffmann-LaRoche, Merck, Merck Sharp & Dohme, Novartis and Pfizer. Please see the abstract for all other authors’ relevant financial disclosures.

 

 

BARCELONA — First-line pembrolizumab monotherapy conferred a durable long-term OS benefit compared with chemotherapy for patients with metastatic, PD-L1-expressing non-small cell lung cancer, according to 3-year survival results of the KEYNOTE-024 trial presented at International Association for the Study of Lung Cancer World Conference on Lung Cancer.

“Immunotherapy has completely changed the management of lung cancer. We’re changing lung cancer to a chronic disease with good quality of life,” Martin Reck, MD, PhD, head of the thoracic oncology service at Lung Clinic Grosshansdorf in Germany, said during a press conference. “What we have seen is that immunotherapy with pembrolizumab is a monotherapy opportunity for first-line treatment of patients with PD-L1 expression as well as in combination with chemotherapy for patients regardless of PD-L1 expression.”

The phase 3 KEYNOTE-024 trial evaluated the safety and efficacy of pembrolizumab vs. platinum-based chemotherapy as first-line treatment for patients with advanced NSCLC who have a PD-L1 tumor proportion score of 50% or greater but do not have targetable EGFR/ALK aberrations.

Reck and colleagues randomly assigned 305 participants in the trial to pembrolizumab (Keytruda, Merck) dosed at 200 mg every 3 weeks for up to 2 years (n = 154) or four to six cycles of platinum doublet chemotherapy (at the investigator’s discretion) plus optimal maintenance for those with nonsquamous disease (n = 151). The study design allowed eligible patients in the chemotherapy group who experienced disease progression to cross over to pembrolizumab.

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

Median follow-up at data cutoff of Feb. 15 was 44.4 months (range, 39.6-52.9).

By that time, 210 patients had died, including 97 in the pembrolizumab group and 113 in the chemotherapy group. Ninety-eight patients (64.9%) crossed over from chemotherapy to anti-PD-L1 therapy during or outside of the study interval.

Results showed median OS of 26.3 months (95% CI, 18.3-40.4) in the pembrolizumab group vs. 14.2 months (95% CI, 9.8-18.3) in the chemotherapy group (HR = 0.65; 95% CI, 0.5-0.86). The 36-month OS rate was 43.7% with pembrolizumab vs. 24.9% with chemotherapy.

Although mean duration of treatment was longer with pembrolizumab vs. chemotherapy (11.1 vs. 4.4 months), grade 3 to grade 5 treatment-related adverse events occurred less frequently with pembrolizumab (31.2% vs. 53.3%).

“Then we looked at immune-related adverse events, and the question was, what are we inducing when we treat patients for 2 years?” Reck said. “Interestingly, we haven’t seen a lot of changes in the frequencies of immune-mediated adverse events. Thirty-four patients do have immune-mediated adverse events but when we look at the kind of immune-mediated adverse events, they are the same as the ones we’ve seen.”

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These include infusion reactions, gastrointestinal events and pulmonary toxicities, Reck added.

Thirty-eight patients in the pembrolizumab group finished 2 years (35 cycles) of therapy. Among these patients, 34 remained alive, 31 (81.6%) demonstrated an objective response (including three with complete response) and median duration of response was not reached (range, 4.2-46.7+). Five (13.2%) patients had treatment-related grade 3 to grade 4 adverse events, none of which resulted in death.

At data cutoff, 71% of patients with a duration of response of at least 2 years had stable disease without the need for additional treatment, Reck said.

Reck also presented data on 10 patients who progressed after 2 years of pembrolizumab and underwent a second course of the treatment; seven had an objective response and eight are alive.

“We are confirming the efficacy of pembrolizumab in this long-term analysis, with a consistent OS benefit, and we see this benefit despite the crossover of 65%,” Reck said. “We have also seen preliminary results that demonstrate the feasibility of a second course of pembrolizumab, and that response is achievable despite prior exposure to pembrolizumab.” – by Jennifer Byrne

Reference:

Reck M, et al. Abstract OA14.01. Presented at: International Association for the Study of Lung Cancer World Conference on Lung Cancer; Sept. 7-10, 2019; Barcelona.

Disclosures: Reck reports honoraria from and consultant/advisory or speakers’ bureau roles with AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Celgene, Eli Lilly, F. Hoffmann-LaRoche, Merck, Merck Sharp & Dohme, Novartis and Pfizer. Please see the abstract for all other authors’ relevant financial disclosures.

 

 

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