Takeaways From Lung-MAP Substudy S1800A in NSCLC

Karen L. Reckamp, MD, MS, professor in Medicine, director of the Division of Medical Oncology at Cedars-Sinai Medical Center, discusses findings from the phase 2 Lung-MAP substudy S1800A (NCT03971474) which examined the combination of pembrolizumab (Keytruda) and ramucirumab (Cyramza) in patients with stage IV, previously-treated non–small cell lung cancer (NSCLC).

The study evaluated the combination in patients who had acquired resistance to an immune checkpoint inhibitor (ICI). This acquired resistance was defined as previous ICI therapy for at least 84 days with progressive disease on or after therapy.

Findings of the S1800A substudy showed there to be an overall survival (OS) benefit with the combination compared with the standard of care (SOC) in this patient population. Treatment with ramucirumab/pembrolizumab elicited a median OS of 15.0 (95% CI, 13.2-17) vs 11.6 months (95% CI, 8.5-13.8) with the SOC (HR, 0.61; 95% CI, 0.38-0.97; 1-sided P =0.019).

Further, progression-free survival (PFS) was similar between treatment arms (HR, 0.86; 95% CI, 0.57-1.31; 1-sided P =0.25), with the median PFS in the ramucirumab/pembrolizumab arm at 4.5 months (95% CI, 4.0-6.9) compared with 5.2 months (95% CI, 4.0-6.6) in the SOC arm.

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0:08 | We evaluated the outcomes of overall survival by PD-L1 status and there was no difference based on PD-L1 status for all patients receiving ramucirumab and pembrolizumab. By performance status, we did see an increased benefit in patients who had squamous cell or mixed histologies, but again, there was benefit across all subgroups.

0:35 | Importantly, this was a patient population that had received at least 84 days of prior immune checkpoint inhibitor therapy before experiencing tumor progression. And so, this is an acquired resistance population. In this population, we now see an overall survival benefit with the combination of ramucirumab and pembrolizumab as a non-chemotherapy option, and against the most potent regimen that we had in the second-line docetaxel/ramucirumab. We are hoping to move this forward into a phase 3 trial to better understand the magnitude of benefit of this combination.