KEY TAKEAWAYS
- MAP S1800A phase II sub-study (NCT03971474) comparatively evaluates the OS of patients with aNSCLC upon intake of RP and SoC.
- The study primarily aims to compare RP and SOC’s OS rates.
- Researchers evaluated 136 patients for OS upon intake of RP and SoC using SLR and WLR.
- The study resulted in RP group showing statistically significant improvement in OS than SOC, with no difference in response rates and progression-free survival.
The development of resistance to immune checkpoint inhibition (ICI) is a significant unmet need in patients with advanced non-small-cell lung cancer (NSCLC). Several tumor types have shown improvement after combining ICI with VEGF/VEGF receptor inhibition.
Patients with NSCLC who were unfit for a biomarker-matched substudy were randomly assigned to receive either ramucirumab plus pembrolizumab (RP) or the investigator’s choice standard of care (SOC: docetaxel/ramucirumab, docetaxel, gemcitabine, and pemetrexed) in this phase II Lung-MAP nonmatch substudy (S1800A). The primary purpose was to compare overall survival (OS) at a one-sided 10% level utilizing the better of a standard log-rank (SLR) and weighted log-rank (WLR; G [rho = 0, gamma = 1]) test with a target of 130 eligible patients. Objective response, duration of response, progression-free survival as determined by the investigator, and toxicity were secondary endpoints.
Just 136 of the 166 recruited patients were eligible for the study (69 RP; 67 SOC). A statistically significant increase in OS (hazard ratio [80% CI]: 0.69 [0.51 to 0.92]; SLR one-sided P =.05; WLR one-sided P =.15) was observed in the RP group. OS for RP was 14.5 months (95% CI: 13.91 to 16.11), and for SOC, it was 11.6 months (95% CI: 9.9 to 13.0). Most subgroups saw an improvement in OS after receiving RP. Response rates (22% RP v 28% SOC, one-sided P =.19) and progression-free survival (hazard ratio [80% CI]: 0.86 [0.66 to 1.14]; one-sided SLR, P =.25 and.14 for WLR) were similar between arms, as were overall survival rates. About 42% of patients in the RP group and 60% of those on SOC experienced treatment-related adverse events of grade 3 or above.
In this randomized phase II trial, individuals with advanced NSCLC who had previously been treated with ICI and chemotherapy benefited greatly from RP compared to SOC in terms of overall survival. The risk was within the range of possible adverse effects for both medicines. There needs to be more analysis of these numbers.
Source: https://pubmed.ncbi.nlm.nih.gov/35658002/
Clinical trial: https://clinicaltrials.gov/ct2/show/NCT03971474
Reckamp, K. L., Redman, M. W., Dragnev, K. H., Minichiello, K., Villaruz, L. C., Faller, B., Al Baghdadi, T., Hines, S., Everhart, L., Highleyman, L., Papadimitrakopoulou, V., Neal, J. W., Waqar, S. N., Patel, J. D., Gray, J. E., Gandara, D. R., Kelly, K., & Herbst, R. S. (2022). Phase II Randomized Study of Ramucirumab and Pembrolizumab Versus Standard of Care in Advanced Non-Small-Cell Lung Cancer Previously Treated With Immunotherapy-Lung-MAP S1800A. Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology, 40(21), 2295–2306. https://doi.org/10.1200/JCO.22.00912
