Pembrolizumab Combos Miss Survival End Points in Metastatic NSCLC

In the final analysis of the phase 3 LEAP-006 trial (NCT03829319), pembrolizumab plus lenvatinib, pemetrexed, and platinum-based chemotherapy did not yield improvements in OS vs pembrolizumab plus pemetrexed and chemotherapy in those with metastatic nonsquamous NSCLC for which EGFR-, ALK-, or ROS1-directed therapy is not indicated.

Combining pembrolizumab (Keytruda) with lenvatinib (Lenvima) did not improve progression-free or overall survival (OS) compared with standard-of-care options in select patients with metastatic non–small cell lung cancer (NSCLC) in 2 phase 3 studies, according to a news release from Merck and Eisai, the developers of the respective agents.

In the final analysis of the phase 3 LEAP-006 trial (NCT03829319), pembrolizumab plus lenvatinib, pemetrexed, and platinum-based chemotherapy did not yield improvements in OS vs pembrolizumab plus pemetrexed and chemotherapy in those with metastatic nonsquamous NSCLC for which EGFR-, ALK-, or ROS1-directed therapy is not indicated. Additionally, investigators reported that there were no improvements in progression-free survival (PFS) nor objective response rate (ORR) in the pembrolizumab/lenvatinib arm at the time of earlier interim analyses.

Similarly, in the final analysis of the phase 3 LEAP-008 trial (NCT03976375), pembrolizumab plus lenvatinib did not produce an improvement in OS compared with docetaxel in patients with metastatic NSCLC that has progressed following platinum-based chemotherapy and at least 1 PD-1/PD-L1 inhibitor for which no EGFR-, ALK-, or ROS1-directed therapy is indicated. Treatment with pembrolizumab and lenvatinib also did not significantly improve PFS or ORR compared with docetaxel.

The safety profiles of pembrolizumab plus lenvatinib in both phase 3 trials were comparable with prior reports of the regimen. Developers and investigators look to collaborate and share their findings with the scientific community.

“As a leader in lung cancer research, we continue to try to advance science for our patients by building upon the standard we set several years ago with [pembrolizumab],” Gregory Lubiniecki, MD, vice president of global clinical development at Merck Research Laboratories, said in the news release. “While these results are not what we hoped for, we are proud of the foundational role that [pembrolizumab] has established in the treatment of certain types of lung cancer, and we are committed to continuing to research how we can further improve responses to our medicines for patients with difficult-to-treat forms of the disease.”

In the randomized phase 3 LEAP-006 trial, approximately 748 patients were randomly assigned 1:1 to receive frontline pembrolizumab at 200 mg intravenously once every 3 weeks with or without 8 mg of lenvatinib once daily. Additionally, all patients received 500 mg/m² of pemetrexed intravenously once every 3 weeks plus carboplatin at area under curve 5 mg/ml per minute or cisplatin at 75 mg/m² intravenously once every 3 weeks.

The LEAP-006 trial’s primary end points were PFS per blinded independent central review based on modified RECIST v1.1 criteria and OS. Secondary end points included ORR, duration of response (DOR), quality of life, and safety.

In the open-label phase 3 LEAP-008 trial, investigators assigned approximately 422 patients 4:4:1 to receive 200 mg of intravenous pembrolizumab every 3 weeks plus 20 mg of lenvatinib orally once daily, 75 mg/m² of docetaxel intravenously every 3 weeks, or lenvatinib alone at 24 mg orally once daily.

The trial’s primary end points were PFS and OS. Secondary end points included ORR, DOR, quality of life, and safety.

“[Pembrolizumab] plus [lenvatinib] has demonstrated survival benefit in advanced renal cell carcinoma and advanced endometrial carcinoma, and while we are disappointed that the final analyses of these [NSCLC] studies did not show the same benefit, we remain committed to applying learnings from these studies and furthering research in oncology for people with unmet needs,” Corina Dutcus, MD, senior vice president of global clinical development of oncology at Eisai Inc., concluded in the release.

Reference

Merck and Eisai provide update on two phase 3 trials evaluating KEYTRUDA® (pembrolizumab) plus LENVIMA® (lenvatinib) in patients with certain types of metastatic non-small cell lung cancer. News release. Merck and Eisai. September 22, 2023. Accessed September 25, 2023. https://shorturl.at/kvX08