Keytruda OK’d as First-Line Tx in Advanced, Squamous NSCLC

Click here to view original web page at www.medpagetoday.com

The FDA has yet again expanded the indication of pembrolizumab (Keytruda) to now include the first-line treatment of metastatic squamous cell non-small cell lung cancer (NSCLC) in combination with chemotherapy.

The approval was based on findings from the KEYNOTE-407 trial, which showed an improved median overall survival (OS) in squamous NSCLC patients treated with the PD-1 inhibitor pembrolizumab plus chemotherapy (carboplatin and either paclitaxel or nab-paclitaxel) compared to those treated with chemotherapy plus placebo (15.9 versus 11.3 months, HR 0.64, 95% CI 0.49-0.85, P<0.001).

"The results that support this approval from the KEYNOTE-407 trial demonstrate the potential of Keytruda in combination with chemotherapy in patients with squamous non-small cell lung cancer, regardless of PD-L1 expression," investigator Balazs Halmos, MD, of Montefiore Einstein Center for Cancer Care in New York City, said in a statement from the manufacturer. "With this important approval, more patients will have the opportunity to benefit from immunotherapy."

At 6.4 versus 4.8 months, median progression-free survival (PFS) was also higher in the pembrolizumab group (HR 0.56, 95% CI 0.45-0.70, P<0.001). And PFS favored the PD-1 inhibitor-treated group in all pre-specified subgroups -- Eastern Cooperative Oncology Group (ECOG) performance status 0-1, sex, age, type of chemotherapy, and PD-L1 expression levels.

OS results were consistent across most pre-specified subgroups, including PD-L1 expression level:

  • <1%: HR 0.61 (95% CI 0.38-0.98)
  • ≥1%: HR 0.65 (95% CI 0.45-0.92)
  • 1% to 49%: HR 0.57 (95% CI 0.36-0.90)
  • ≥50%: HR 0.64 (95% CI 0.37-1.10)

Halmos recently presented findings from an exploratory analysis of KEYNOTE-407 based on investigator's choice of chemotherapy at the World Conference on Lung Cancer -- 60.1% of patients in the study received paclitaxel and 39.9% received nab-paclitaxel. The overall survival HRs for pembrolizumab-treated patients were 0.67 with paclitaxel (95% CI 0.48-0.93) and 0.59 with nab-paclitaxel (95% CI 0.36-0.98), respectively.

The rate of overall response was similar between the two (57.4% versus 58.7%, respectively), but grade ≥3 adverse events (AEs) were slightly less frequent with paclitaxel (63.9% versus 78.9%).

KEYNOTE-407 was a double-blind, multicenter trial that randomized 559 patients with metastatic, previously untreated squamous NSCLC (1:1) to treatment with four cycles of carboplatin and either paclitaxel or nab-paclitaxel plus 200-mg pembrolizumab or placebo for up to 35 cycles.

Overall, AEs were similar between the two treatment arms, with grade ≥3 AEs occurring in 69.8% of the pembrolizumab group versus 68.2% of the placebo group.

In the FDA's release, they noted that the most common AEs (≥20% of patients) with pembrolizumab were asthenia, nausea and vomiting, constipation, diarrhea, pyrexia, decreased appetite, rash, cough, dyspnea, alopecia, and peripheral neuropathy.


Related posts

Leave a Comment

This site uses Akismet to reduce spam. Learn how your comment data is processed.