CheckMate 9LA Combination Effective in Advanced NSCLC Despite PD-L1 Expression, TMB Status

CheckMate 9LA Combination Effective in Advanced NSCLC Despite PD-L1 Expression, TMB Status

Meeting News
Apr 23, 2021
Leah Lawrence
European Lung Cancer Virtual Congress image

A higher tumor mutational burden (TMB) was associated with improved PFS and overall response rate for patients with advanced NSCLC treated with nivolumab plus ipilimumab plus chemotherapy compared with chemotherapy alone, according to results from CheckMate 9LA presented at the European Lung Cancer Virtual Congress 2021.1 

No differences in outcomes among treatment arms were seen among patients with low TMB, and OS benefit was similar between those with low and high TMB.

In CheckMate 9LA, combination treatment with immunotherapy and two cycles of chemotherapy significantly improved OS compared with four cycles of chemotherapy alone for patients with advanced NSCLC. Benefits were seen regardless of PD-L1 expression. This secondary analysis examined whether TMB was associated with clinical efficacy of immune checkpoint inhibitors. 

Luis Paz-Ares, MD, PhD, chief physician at the Hospital Universitario 12 de Octubre, Madrid, Spain, presented the results of the trial, which included 711 patients who were randomly assigned to nivolumab plus ipilimumab plus chemotherapy or to chemotherapy alone, with available tissue (64%) and blood (73%) TMB data. 

Baseline characteristics were comparable between patients evaluated for tissue and blood TMB. OS, PFS, and overall response rate for the tissue TMB and blood TMB subgroups were generally consistent with those in the all-randomized population, according to Dr. Paz-Ares. 

Overall response rate was higher for those patients with high TMB in tissue and blood who were treated with the combination, compared to those with low TMB. 

PFS in the high tissue TMB subgroup (10 or more mutations per megabase) was significantly longer for patients treated with nivolumab plus ipilimumab plus chemotherapy (HR 0.49, 95% CI [0.34-0.70]) compared with those receiving chemotherapy-alone; there was no significant difference between treatments for patients in the low tissue TMB subgroup (HR 0.83, 95% CI [0.63-1.10]). 

Similarly, patients with high blood TMB (16 or more mutations per megabase) had significantly improved PFS with combination treatment compared with chemotherapy alone (HR 0.55, 95% CI [0.39-0.78]); no difference was seen in the low blood TMB subgroup. 

However, in terms of OS, the benefit was similar between patients with high tissue TMB compared with low tissue TMB, as well as the subgroups of blood TMB for cutoffs of both 16 and 20 mutations per megabase.

“PD-L1 expression did not appear to affect the magnitude of OS benefit with nivolumab plus ipilimumab plus chemotherapy versus chemotherapy in different TMB subgroups,” Dr. Paz-Ares said. “Along with the previously reported data from CheckMate 9LA, these results support the use of nivolumab plus ipilimumab plus two cycles of chemotherapy as first-line treatment for patients with advanced NSCLC regardless of PD-L1 expression, TMB status, or their combination.” 

Disclosure: This study was sponsored by Bristol Myers Squibb.

 

References
  • 1. Paz-Ares L, Ciuleanu T, Cobo Dols M, et al. 98O - First-line nivolumab (NIVO) + ipilimumab (IPI) + 2 cycles chemotherapy (chemo) vs 4 cycles chemo in advanced non-small cell lung cancer (aNSCLC): association of blood and tissue tumor mutational burden (TMB) with efficacy in CheckMate 9LA. Paper presented at: European Lung Cancer Virtual Congress 2021; March 25, 2021. Accessed April 7, 2021. https://oncologypro.esmo.org/meeting-resources/european-lung-cancer-vir…

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