medwireNews: Ramucirumab plus pembrolizumab significantly improves overall survival (OS) versus standard of care in people with advanced non-small-cell lung cancer (NSCLC) previously treated with immunotherapy and chemotherapy, phase 2 Lung-MAP Protocol substudy data show.
Speaking at the 2022 ASCO Annual Meeting in Chicago, Illinois, USA, Karen Reckamp (Cedars-Sinai Medical Center, Los Angeles, California, USA) explained that Lung-MAP is a US-wide precision medicine, “master protocol for patients with stage IV or recurrent, previously treated NSCLC.”
Participants can be enrolled in either biomarker-driven or unmatched substudies, such as S1800A, which was presented by Reckamp. All participants had received prior treatment with an immune checkpoint inhibitor (ICI) and platinum-based chemotherapy, and had progressive disease at least 84 days after ICI initiation.
Reckamp reported that median OS was 14.5 months among the 69 patients who were randomly assigned to receive the VEGFR2 inhibitor ramucirumab 10 mg/kg plus the anti-PD1 antibody pembrolizumab 200 mg every 3 weeks for up to 35 cycles.
This was significantly longer than the median OS of 11.6 months among the 67 given investigator's choice of docetaxel plus ramucirumab (n=45), gemcitabine (n=12), docetaxel (n=3), pemetrexed (n=1), or no treatment (n=6). The difference equated to a hazard ratio (HR) for death of 0.69 in favor of ramucirumab plus pembrolizumab.
Discussant Christine Bestvina, from the University of Chicago, said the fact that a high proportion of participants in the control arm received ramucirumab was “reassuring,” because it shows that “the benefit observed here in this trial is not just receiving [ramucirumab] in the second-line, it’s rather the synergistic benefit” of immunotherapy plus ramucirumab.
Reckamp showed that the OS benefit with ramucirumab plus pembrolizumab was generally consistent across subgroups, including those stratified by PD-L1 expression level and performance status.
Individuals with squamous or mixed histology (n=57) appeared to derive greater benefit than those with nonsquamous histology (n=79); the exploratory HRs were a significant 0.43 and nonsignificant 0.95, respectively.
In addition, the magnitude of benefit with ramucirumab plus pembrolizumab was greater for people who received prior chemotherapy and immunotherapy sequentially (n=59) than those who received the treatments concurrently (n=74), with a significant HR for death of 0.45 in the former subgroup and a nonsignificant HR of 0.84 in the latter.
Bestvina commented that “this is important for us all to acknowledge given that most of our patients are receiving combination [chemoimmunotherapy] as front-line therapy.”
Biomarker analysis suggested that individuals who carry STK11 mutations (n=17) also had a pronounced OS benefit when receiving ramucirumab plus pembrolizumab (HR=0.23), but the numbers in this analysis were small and “will require future evaluation,” Reckamp remarked.
Although OS was superior with ramucirumab plus pembrolizumab, investigator-assessed progression-free survival (PFS; median, 4.5 vs 5.2 months) and objective response rates (22 vs 28%) were similar between arms. Median response duration was 12.9 months with ramucirumab plus pembrolizumab and 5.6 months with standard of care.
The presenter noted that discordance between PFS and OS has been seen in previous ICI trials and has been described as postprogression prolongation of survival.
In terms of safety, grade 3 or worse adverse events (AEs) occurred in 42% of patients in the ramucirumab plus pembrolizumab arm and in 60% of those in the control arm, with AEs consistent with known toxicities of both drugs.
Reckamp concluded: “This is the first trial in the ICI-refractory setting to improve overall survival compared to standard of care in which most patients received docetaxel plus ramucirumab in the control arm, which also performed better than in historical trials.”
She added that the team now hopes to perform a phase 3 trial in the same setting.
Bestvina said that in her opinion the data are “practice changing tomorrow,” but she is not convinced that ramucirumab plus pembrolizumab is best for all patients.
The study was simultaneously published in the Journal of Clinical Oncology.
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2022 ASCO Annual Meeting; Chicago, Illinois, USA: 3–7 June
J Clin Oncol 2022; doi:10.1200/JCO.22.00912