Pemetrexed, bevacizumab maintenance therapy benefits certain NSCLC subsets

CHICAGO — Adding pemetrexed to continuous maintenance therapy with bevacizumab after induction therapy with carboplatin, pemetrexed and bevacizumab did not significantly improve OS among patients with non-squamous, non-small cell lung cancer without sensitizing EGFR mutations, according to results of the phase 3 COMPASS trial.

Although the trial failed to meet its primary endpoint of OS in the overall population, the addition of pemetrexed to continuous maintenance therapy with bevacizumab (Avastin, Genentech) did significantly prolong PFS, as well as OS among patients aged younger than 70 years and those with wild-type EGFR mutations.

During a presentation at the ASCO Annual Meeting, Takashi Seto, MD, of the National Kyushu Cancer Center in Japan, said the results suggest that “diverse pemetrexed continuation maintenance is an essential part of first-line carboplatin, pemetrexed-based combination therapy.”

For the trial, Seto and colleagues assigned 907 previously untreated patients with advanced, non-squamous NSCLC whose EGFR status did not include exon 19 deletion or L858R mutations to receive four cycles of induction treatment with carboplatin, pemetrexed (500 mg/m²) and bevacizumab (15 mg/kg) every 3 weeks. Wild-type or unknown EGFR status was also acceptable. Patients who did not progress during induction therapy were randomly assigned to continuous maintenance therapy with bevacizumab plus pemetrexed (n = 299) or bevacizumab alone (n = 295). The primary endpoint was OS.

The median follow-up duration was 59.9 months (95% CI, 56.4-62.5 months). Median OS was 23.3 months among patients who received bevacizumab plus pemetrexed and 19.6 months among those who received bevacizumab alone. The higher median OS in the bevacizumab plus pemetrexed arm was not clinically significant. However, bevacizumab plus pemetrexed substantially prolonged median PFS, which was 5.7 months vs. 4 months, respectively (HR = 0.67; 95% CI, 0.57-0.79).

Further investigation revealed that the addition of pemetrexed to bevacizumab significantly increased median OS among patients aged younger than 70 years (23.7 months vs. 19.7 months; HR = 0.79; 95% CI, 0.64-0.98) and patients with wild-type EGFR status (23.3 months vs. 18.8 months; HR = 0.82; 95% CI, 0.68-0.99).

No new toxicities related to the study treatment were observed, according to Seto. The research team is currently conducting another phase 3 trial to assess the benefit of adding bevacizumab to induction therapy with carboplatin, pemetrexed and atezolizumab (Tecentriq, Genentech), followed by maintenance therapy with atezolizumab and pemetrexed. – by Stephanie Viguers

References:

Seto T, et al. Abstract 9003. Presented at: ASCO Annual Meeting; May 31-June 4, 2019; Chicago.

Disclosure: Seto reports receiving honoraria from Astellas Pharma, AstraZeneca, Bristol-Myers Squibb, Chugai Pharma, Eli Lilly and Company, Merck, Nippon Boehringer Ingelheim, Novartis, Ono Pharmaceutical, Pfizer, Taiho Pharmaceutical, Takeda and Thermo Fisher Scientific and research funding on behalf of his institution from AstraZeneca, Bayer Yakuhin, Chugai Pharma, Daiichi Sankyo, Eli Lilly and Company, Kissei Pharmaceutical, Loxo, Merck, Nippon Boehringer Ingelheim, Novartis, Pfizer and Takeda.