Adding Bevacizumab to Maintenance Pemetrexed Improves PFS in Advanced Nonsquamous NSCLC

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Maintenance therapy with bevacizumab plus pemetrexed improved progression-free survival compared with pemetrexed alone.
Maintenance therapy with bevacizumab plus pemetrexed improved progression-free survival compared with pemetrexed alone.

Maintenance therapy with bevacizumab plus pemetrexed improved progression-free survival compared with pemetrexed alone in patients with advanced, nonsquamous non-small cell lung cancer (NSCLC), a study presented at the European Lung Cancer Conference (ELCC) 2016 has shown.1 However, adding bevacizumab did not improve overall survival.

Because the PARAMOUNT trial established maintenance therapy to be effective with pemetrexed in patients with advanced, nonsquamous NSCLC and the AVAPERL trial demonstrated encouraging efficacy with bevacizumab plus pemetrexed compared with bevacizumab alone, researchers sought to compare maintenance therapy with bevacizumab plus pemetrexed with pemetrexed alone.

For the phase 2 trial, researchers enrolled 77 patients into the first cohort and treated them with cisplatin 75 mg/m2, pemetrexed 500 mg/m2, and bevacizumab 7.5 mg/kg every 3 weeks for 4 cycles. Patients then received maintenance therapy with bevacizumab plus pemetrexed until disease progression.

A second cohort of 52 patients received the same chemotherapy, but without bevacizumab and outcomes were compared.

Results showed that median progression-free survival was 6.9 months (95% CI, 5.2 - 8.4) with bevacizumab plus pemetrexed vs 5.6 months (95% CI, 4.3 - 6.8) with pemetrexed alone (HR, 0.7; 95% CI, 0.5 - 1.0; P = .04).

Overall response was 62% (95% CI, 51 - 73) and 44% (95% CI, 31 - 59) with bevacizumab plus pemetrexed and single-agent pemetrexed, respectively (odds ratio, 2.1; 95% CI, 1.0 - 4.3; P = .05).

In contrast, investigators observed no significant difference in overall survival between the 2 cohorts after a median follow-up of 47 months for patients who received the combination and 27 months for patients who received pemetrexed alone (HR, 1.0; 95% CI, 0.7 - 1.6; P = .89).

In terms of safety, patients in the chemoimmunotherapy cohort experienced a slightly higher rate of grade 3 or worse adverse events than those treated with pemetrexed.

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In addition, a preliminary economic analysis demonstrated that treatment costs were approximately 1.6 times higher with bevacizumab plus pemetrexed vs pemetrexed alone.

An ongoing phase 3 trial is comparing the overall survival impact of bevacizumab and pemetrexed maintenance therapy with that of single-agent pemetrexed maintenance.

Reference

  1. Gautschi O, Li Q, Matter-Walstra K, et al. Bevacizumab and pemetrexed versus pemetrexed alone as maintenance therapy for patients with advanced nonsquamous NSCLC: results of the expanded SAKK19/09 trial. Poster presentation at: European Lung Cancer Conference 2016; April 13-16, 2016; Geneva, Switzerland.

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