Compared with the current standard of care, combination pembrolizumab plus ramucirumab improved overall survival (OS) outcomes among patients with previously treated, advanced non-small cell lung cancer (NSCLC), according to research presented at the 2022 ASCO Annual Meeting.

Although immune checkpoint inhibitors have generally improved outcomes for many patients with NSCLC, most patients with advanced disease develop resistance to these treatments. Furthermore, few treatment options are available in this setting.

There is, however, evidence that combining immune checkpoint inhibitors with VEGF/VEGF receptor inhibitors may be effective in this patient population. For this sub-study of the LUNG-MAP protocol, researchers evaluated combination pembrolizumab plus ramucirumab among patients with stage IV disease who had previously been treated with an immune checkpoint inhibitor ( Identifier: NCT03971474).

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Patients were randomly assigned to receive standard of care (investigator’s choice of docetaxel plus ramucirumab or docetaxel, pemetrexed, and gemcitabine) or pembrolizumab plus ramucirumab. Patients were stratified by PD-L1 expression and disease histology.

Overall, 136 eligible patients enrolled in this study between 2019 and 2020 and were included in the analysis; 67 and 69 were assigned to the standard of care and experimental groups, respectively. In the standard of care and experimental groups, the median ages were 65.8 and 66.4 years, respectively, 63% and 59% of patients were men, and 58% and 52% of patients had adenocarcinoma, which was the most common disease histology in the cohort.

The results showed that pembrolizumab plus ramucirumab improved OS (hazard ratio, 0.69; P =.05). The median OS was 14.5 months with the experimental combination and 11.6 months in the standard care arm. All subgroups, including patients with co-mutations and regardless of PD-L1 status, had hazard ratios of less than 1 in the experimental arm.

There was, however, no significant difference in progression-free survival or overall response rates between the treatment arms.

“Discordance of objective response rates and progression-free survival from overall survival has previously been reported in immune checkpoint inhibitor trials, suggesting postprogression prolongation of survival,” reported Karen L. Reckamp, MD, of Cedars-Sinai Medical Center in Los Angeles, California, the study’s presenter.

Grade 3 or higher treatment-related adverse events occurred more often in the standard of care arm (60%) than in the pembrolizumab-ramucirumab arm (42%).

Disclosures: This research was supported, in part, by Eli Lilly and Company and Merck & Co Inc. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.


Reckamp KL, Redman MW, Dragnev KH, et al. Overall survival from a phase II randomized study of ramucirumab plus pembrolizumab versus standard of care for advanced non–small cell lung cancer previously treated with immunotherapy: Lung-MAP nonmatched substudy S1800A. Presented at ASCO 2022; June 3-7, 2022. Abstract 9004.