The FDA recently approved pembrolizumab in combination with carboplatin and either paclitaxel or nab-paclitaxel as first-line treatment of metastatic squamous non-small cell lung cancer (NSCLC).
Approval was based on KEYNOTE-407 (NCT02775435), a randomized, multi-center, double-blind, placebo-controlled trial in 559 patients with metastatic squamous NSCLC, regardless of PD-L1 tumor expression status, who had not previously received systemic therapy for metastatic disease.
Patients were randomized (1:1) to pembrolizumab 200 mg or placebo in combination with carboplatin, and investigator's choice of either paclitaxel every 3 weeks or nab-paclitaxel weekly on a 3-week cycle for 4 cycles followed by pembrolizumab or placebo. Patients continued pembrolizumab or placebo until disease progression, unacceptable toxicity, or a maximum of 24 months.
The main efficacy outcome measures were overall survival (OS), progression-free survival (PFS), and overall response rate (ORR) as assessed by blinded independent review. The trial demonstrated statistically significant improvements in OS, PFS, and ORR for patients receiving pembrolizumab plus chemotherapy compared with those randomized to placebo plus chemotherapy. The median OS was 15.9 and 11.3 months for the pembrolizumab plus chemotherapy and placebo plus chemotherapy arms, respectively (HR 0.64; 95% CI: 0.49, 0.85; p=0.0017). The median PFS was 6.4 and 4.8 months for the pembrolizumab plus chemotherapy and placebo plus chemotherapy arms, respectively (HR 0.56; 95% CI: 0.45, 0.70; p<0.0001). The analysis of ORR was limited to the initial 204 patients randomized. The ORRs were 58 percent and 35 percent, favoring the pembrolizumab-containing arm (difference of 23.6%; 95% CI: 9.9, 36.4; p=0.0008). The estimated median response durations were 7.2 and 4.9 months, respectively.
The most common adverse reactions in at least 20 percent of patients who received pembrolizumab on KEYNOTE-407 were fatigue/asthenia, nausea, constipation, diarrhea, vomiting, pyrexia, decreased appetite, rash, cough, dyspnea, alopecia, and peripheral neuropathy.
The recommended pembrolizumab dose for metastatic squamous NSCLC is 200 mg intravenously every 3 weeks, prior to chemotherapy when given on the same day, until disease progression, unacceptable toxicity, or 24 months after initiation.
"The results that support this approval from the KEYNOTE-407 trial demonstrate the potential of [pembrolizumab] in combination with chemotherapy in patients with squamous non-small cell lung cancer, regardless of PD-L1 expression," said Dr. Balazs Halmos, Director of the Multidisciplinary Thoracic Oncology Program at the Montefiore Einstein Center for Cancer Care and Director of Cinical Cancer Genomics at the Albert Einstein College of Medicine. "With this important approval, more patients will have the opportunity to benefit from immunotherapy."
Pembrolizumab is the first anti-PD-1 approved in the first-line setting as both combination and monotherapy in certain patients with metastatic NSCLC. With this approval, all appropriate patients with metastatic squamous NSCLC and all appropriate patients with metastatic nonsquamous NSCLC and no EGFR or ALK genomic tumor aberrations are now eligible for a pembrolizumab-based regimen as their first-line treatment option.