KEY TAKEAWAYS
- The LEAP-006 phase III trial aimed to test if adding lenvatinib to existing lung cancer treatment improves outcomes.
- The dual primary endpoints were PFS. Secondary endpoints were ORR and safety.
- The result demonstrated that adding lenvatinib to pembro + chemo in lung cancer yielded no survival benefit; pembro + chemo remains standard.
LEAP-006 studied adding a drug called lenvatinib (Len) to the standard treatment for advanced lung cancer (pembrolizumab + chemo). Part 1 of the study figured out the best starting dose for Len. For phase 3 of this study, researchers aimed to test if adding Len to existing lung cancer treatment improved outcomes.
Patients with stage IV nonsquamous NSCLC, without indications for EGFR-, ALK-, or ROS1-directed primary therapy, were randomly assigned in a 1:1 ratio to receive either Len 8 mg/day or matching placebo orally once daily until progression or intolerable toxicity.
All patients received 200 mg of intravenous pembro every 3 weeks in addition to standard doses of carboplatin or cisplatin and pemetrexed for 4 cycles. This was followed by pembro (up to 35 total cycles), and pemetrexed was administered until progression or intolerable toxicity.
The dual primary endpoints were progression-free survival (PFS) based on RECIST 1.1 criteria, independent central review (BICR), and overall survival (OS). Secondary endpoints were objective response rate (ORR) based on RECIST 1.1 by BICR and safety.
The prespecified analysis plan included testing at interim analysis 1 for ORR, interim analysis 3 for PFS, and final analysis for OS. All P values are one-sided.
About 748 patients were randomly assigned to receive Len + Pembro + chemotherapy (n = 375) or placebo + pembro + chemotherapy (n = 373). At the final analysis (FA), the median study follow-up was 36.8 months (28.4-46.4).
At interim analysis 3 (IA3), the median progression-free survival (PFS) (95% CI) was 12.1 months (10.4-14.1) in the Len arm compared to 9.5 months (8.3-10.7) in the placebo arm (HR 0.88 [95% CI 0.74-1.05], P = 0.080).
At FA, the median overall survival (OS) was 21.8 months (18.6-24.0) in the Len arm vs. 22.1 months (19.7-24.2) in the placebo arm (HR 1.05 [95% CI 0.88-1.26], P = 0.708). At interim analysis 1 (IA1), the objective response rate (ORR) was 57.1% (50.1-63.8) in the Len arm compared to 50.7% (43.8-57.6) in the placebo arm (difference 6.3 [95% CI -2.8 to 15.4], P = 0.086).
Treatment-related adverse events (AEs) of grade ≥3 occurred in 69.7% in the Len arm vs. 55.6% in the placebo arm, leading to death in 5.6% vs. 2.7% and resulting in the discontinuation of ≥1 drug in 37.3% vs. 27.7%.
The result demonstrated that adding lenvatinib to pembrolizumab + chemo in lung cancer yielded no survival benefit; pembro + chemo remains standard.
Source: https://cslide.ctimeetingtech.com/immuno23hybrid/attendee/confcal/show/session/23
Clinical Trial: https://clinicaltrials.gov/study/NCT03829319
Herbst RS. Lenvatinib plus pembrolizumab, pemetrexed, and a platinum (len + pembro + chemo) as first-line therapy for metastatic nonsquamous non-small cell lung cancer (NSCLC): phase 3 LEAP-006 study. ESMO IO 2023. Abstract- 64O.
