FDA Approves New First-Line Lung Cancer Treatment

Pembrolizumab is approved in combination with pemetrexed and carboplatin

The US Food and Drug Administration has approval the anti–PD-1 immunotherapy pembrolizumab (Keytruda), in combination with pemetrexed and carboplatin, for patients with untreated metastatic non-squamous non–small-cell lung cancer (NSCLC).

“This approval marks an important milestone in the treatment of lung cancer. Now, pembrolizumab in combination with pemetrexed and carboplatin can be prescribed in the first-line setting for patients with metastatic non-squamous NSCLC, irrespective of PD-L1 expression,” said lead investigator Corey Langer, MD, director of thoracic oncology and professor of medicine at the Hospital of the University of Pennsylvania, in a press release. “Physicians should continue to use each patient’s individual characteristics-including biomarker status, histology, and other clinical factors-to determine the best treatment plan for each person.”

The approval was based on results of a cohort from KEYNOTE-021, an open-label, multi-cohort trial. The study compared 4 cycles of pemetrexed and carboplatin in 63 patients vs pemetrexed/carboplatin plus 200 mg pembrolizumab intravenously every 3 weeks in 60 patients until progression or unacceptable toxicity. Eligible participants had locally advanced or metastatic non-squamous NSCLC and had not previously received any systemic therapy. Patients in either arm could also receive pemetrexed as maintenance therapy at the investigator’s discretion. Patients were randomized by PD-L1 tumor expression (tumor proportion score [TPS] < 1% vs TPS ≥ 1%).

Patients who received pembrolizumab had improved overall response rates and progression-free survival. The overall response rate was 55% in patients who received pembrolizumab plus chemotherapy vs 29% in those who received chemotherapy alone (P = .0032). The median progression-free survival was 13 months with pembrolizumab vs 8.9 months for chemotherapy alone for a hazard ratio of 0.53 (95% CI, 0.31–0.91; P = .0205).

The overall response rate among patients with TPS < 1% was 57% in the pembrolizumab-treated group vs 13% in the chemotherapy-alone group. In patients with TPS ≥ 1%, the overall response rate was 54% in the pembrolizumab-treated group vs 38% in the chemotherapy-alone arm

Serious adverse events in the pembrolizumab arm occurred in 41% of patients vs 28% in those who only received chemotherapy.

The most common adverse events of any grade among patients who received pembrolizumab were constipation (51%), fatigue (71%), and nausea (68%). Grade 3/4 adverse events included dyspnea and fatigue (3.4% each), and diarrhea, nausea, rash, and vomiting (1.7% each).

Ten percent of patients discontinued pembrolizumab due to adverse events, with acute kidney injury (3.4%) as the most common cause.

Pembrolizumab can also cause immune-mediated toxicities including colitis, endocrinopathies, hepatitis, nephritis, and pneumonitis. Based on the severity, pembrolizumab should be either discontinued or withheld, and patients should be given corticosteroids if needed.

The recommended dose of pembrolizumab for NSCLC is 200 mg IV every 3 weeks until progression, unacceptable toxicity, or for 2 years in patients without disease progression.