FDA News

FDA approves Keytruda plus chemotherapy for first-line metastatic squamous NSCLC

The FDA approved pembrolizumab in combination with carboplatin and either paclitaxel or nab-paclitaxel for first-line treatment of metastatic squamous non-small cell lung cancer.

Pembrolizumab (Keytruda, Merck) is the first anti-PD-1 therapy approved for first-line treatment of squamous NSCLC regardless of tumor PD-L1 expression.

“[This] approval expands our current lung cancer indications to include combination treatment in patients with squamous cell carcinoma, a type of lung cancer that is particularly difficult to treat,” Roger M. Perlmutter, MD, PhD, president of Merck Research Laboratories, said in a company-issued press release. “Approval by the FDA has the potential to mean that Keytruda can be used to improve survival for more patients with this debilitating disease.”

The FDA based the approval on results of the randomized phase 3 KEYNOTE-407 trial, which included 559 patients with metastatic squamous NSCLC who had received no prior systemic treatment for metastatic disease. Patients could participate regardless of tumor PD-L1 expression status.

Researchers randomly assigned 278 patients to receive 200 mg pembrolizumab and carboplatin every 3 weeks for four cycles, plus paclitaxel every 3 weeks for four cycles or nab-paclitaxel on days 1, 8 and 15 of every 3-week cycle for four cycles, followed by 200 mg pembrolizumab every 3 weeks.

The other 281 patients received placebo plus the same chemotherapy regimen.

Treatment continued for 24 months, or until disease progression or unacceptable toxicity. Patients assigned placebo were given the opportunity to switch to single-agent pembrolizumab at the time of disease progression.

OS, PFS and objective response rate served as the primary efficacy outcome measures.

Results showed the pembrolizumab regimen significantly improved OS (median, 15.9 months vs. 11.3 months; HR = 0.64; 95% CI, 0.49-0.85), PFS (median, 6.4 months vs. 4.8 months; HR = 0.56; 95% CI, 0.45-0.7) and ORR (58% vs. 35%; P = .0008).

Median duration of response was 7.2 months (range, 2.4-12.4+) with pembrolizumab vs. 4.9 months (range, 2-12.4+) with placebo.

Safety data from the first 101 patients assigned pembrolizumab plus carboplatin and either paclitaxel or nab-paclitaxel showed 15% discontinued treatment due to adverse reactions.

Also, 43% of patients required treatment interruption due to adverse events, the most common of which were thrombocytopenia (20%), neutropenia (11%), anemia (6%), asthenia (2%) and diarrhea (2%).

The most frequent serious adverse reactions were febrile neutropenia (6%), pneumonia (6%) and urinary tract infection (3%).

“The results that support this approval from the KEYNOTE-407 trial demonstrate the potential of Keytruda in combination with chemotherapy [for] patients with squamous non-small cell lung cancer, regardless of PD-L1 expression,” Balazs Halmos, MD, MS, director of the multidisciplinary thoracic oncology program at Montefiore Einstein Center for Cancer Care and director of clinical cancer genomics at Albert Einstein College of Medicine. “With this important approval, more patients will have the opportunity to benefit from immunotherapy.”

The FDA approved pembrolizumab in combination with carboplatin and either paclitaxel or nab-paclitaxel for first-line treatment of metastatic squamous non-small cell lung cancer.

Pembrolizumab (Keytruda, Merck) is the first anti-PD-1 therapy approved for first-line treatment of squamous NSCLC regardless of tumor PD-L1 expression.

“[This] approval expands our current lung cancer indications to include combination treatment in patients with squamous cell carcinoma, a type of lung cancer that is particularly difficult to treat,” Roger M. Perlmutter, MD, PhD, president of Merck Research Laboratories, said in a company-issued press release. “Approval by the FDA has the potential to mean that Keytruda can be used to improve survival for more patients with this debilitating disease.”

The FDA based the approval on results of the randomized phase 3 KEYNOTE-407 trial, which included 559 patients with metastatic squamous NSCLC who had received no prior systemic treatment for metastatic disease. Patients could participate regardless of tumor PD-L1 expression status.

Researchers randomly assigned 278 patients to receive 200 mg pembrolizumab and carboplatin every 3 weeks for four cycles, plus paclitaxel every 3 weeks for four cycles or nab-paclitaxel on days 1, 8 and 15 of every 3-week cycle for four cycles, followed by 200 mg pembrolizumab every 3 weeks.

The other 281 patients received placebo plus the same chemotherapy regimen.

Treatment continued for 24 months, or until disease progression or unacceptable toxicity. Patients assigned placebo were given the opportunity to switch to single-agent pembrolizumab at the time of disease progression.

OS, PFS and objective response rate served as the primary efficacy outcome measures.

Results showed the pembrolizumab regimen significantly improved OS (median, 15.9 months vs. 11.3 months; HR = 0.64; 95% CI, 0.49-0.85), PFS (median, 6.4 months vs. 4.8 months; HR = 0.56; 95% CI, 0.45-0.7) and ORR (58% vs. 35%; P = .0008).

Median duration of response was 7.2 months (range, 2.4-12.4+) with pembrolizumab vs. 4.9 months (range, 2-12.4+) with placebo.

Safety data from the first 101 patients assigned pembrolizumab plus carboplatin and either paclitaxel or nab-paclitaxel showed 15% discontinued treatment due to adverse reactions.

Also, 43% of patients required treatment interruption due to adverse events, the most common of which were thrombocytopenia (20%), neutropenia (11%), anemia (6%), asthenia (2%) and diarrhea (2%).

The most frequent serious adverse reactions were febrile neutropenia (6%), pneumonia (6%) and urinary tract infection (3%).

“The results that support this approval from the KEYNOTE-407 trial demonstrate the potential of Keytruda in combination with chemotherapy [for] patients with squamous non-small cell lung cancer, regardless of PD-L1 expression,” Balazs Halmos, MD, MS, director of the multidisciplinary thoracic oncology program at Montefiore Einstein Center for Cancer Care and director of clinical cancer genomics at Albert Einstein College of Medicine. “With this important approval, more patients will have the opportunity to benefit from immunotherapy.”

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