NIVOLUMAB DEMONSTRATES SLIGHT IMPROVEMENT IN ADVANCED HCC
LBA38_PR: CheckMate 459: A Randomized, Multi-Center Phase 3 Study of Nivolumab (NIVO) vs Sorafenib (SOR) as First-Line (1L) Treatment in Patients (pts) With Advanced Hepatocellular Carcinoma (aHCC)
Thomas Yau
Dr. Thomas Yau (The University of Hong Kong, Hong Kong PRC) presented the results of the phase III trial, CheckMate 459, comparing first-line nivolumab to standard-of-care sorafenib in advanced hepatocellular carcinoma. The primary endpoint of this study was overall survival (OS), while other endpoints such as objective response rate (ORR), progression free survival (PFS), and efficacy stratified by tumor PD-L1 expression were also investigated.
After a minimum 22.8 months of follow-up, the difference in OS between the groups did not meet the prespecified level of statistical significance. For patients treated with nivolumab, the median OS was 16.4 months, compared to 14.7 months when treated with sorafenib (HR 0.85, P = 0.0752). A trend toward higher ORR was observed in the nivolumab group, at 15% vs 7%, with more complete responses in the nivolumab group as well (14 vs 5 patients). The incidence of adverse events was also lower in the nivolumab-treated patients. When patients were stratified by PD-L1 expression, a seemingly greater benefit was observed for PD-L1+ patients treated with nivolumab: ORR was 28% for PD-L1+ nivolumab-treated patients, and 9% for PD-L1+ sorafenib-treated patients. Thus, while statistical significance was not achieved in this study, the enhanced safety profile of nivolumab and potential benefit for PD-L1+ patients merit future investigation.
TUMOR MUTATIONAL BURDEN AND PD-L1 POINT TO PEMBROLIZUMAB RESPONDERS
LBA79: Association between tissue TMB (tTMB) and clinical outcomes with pembrolizumab monotherapy (pembro) in PD-L1 positive advanced NSCLC in the KEYNOTE-010 and -042 trials
Roy S. Herbst
An exploratory analysis of tissue tumor mutational burden (tTMB) and outcomes of NSCLC patients on pembrolizumab treatment was presented by Dr. Roy S. Herbst (Yale Cancer Center, New Haven, CT). Patient cohorts from two previous studies of pembrolizumab in NSCLC, KEYNOTE-010 and KEYNOTE-042, were retrospectively analyzed for correlations of response and tTMB. Notably, these patients were all PD-L1+. tTMB was measured through whole exome sequencing of both tumor and normal matched DNA.
tTMB could be evaluated in 24% of KEYNOTE-010 patients and 62% of those from KEYNOTE-042, and was not correlated with PD-L1 TPS in any cohorts, whether treated with pembrolizumab or chemotherapy. Significant associations were observed between tTMB and OS, PFS, and ORR for patients treated with pembrolizumab (all p < 0.01) in both studies. However, tTMB did not correlate with response to chemotherapy. Overall, improved outcomes were observed for patients with high tTMB (>175 mut/exome) treated with pembrolizumab, compared to their low-tTMB counterparts. For example, the OS hazard ratio in KEYNOTE-010 was 0.56 (0.38-0.83) for tTMB-high vs tTMB-low, and 0.62 (0.48-0.80) in KEYNOTE-042 as well. Thus, tTMB may provide added value toward prediction of NSCLC pembrolizumab monotherapy responders, but needs to be evaluated prospectively.