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Randomized Controlled Trial
. 2019 Sep 10;37(26):2360-2367.
doi: 10.1200/JCO.19.01006. Epub 2019 Jul 30.

Pemetrexed, Bevacizumab, or the Combination As Maintenance Therapy for Advanced Nonsquamous Non-Small-Cell Lung Cancer: ECOG-ACRIN 5508

Suresh S Ramalingam  1 , Suzanne E Dahlberg  2 , Chandra P Belani  3 , Joel N Saltzman  4 , Nathan A Pennell  5 , Gopakumar S Nambudiri  6 , John C McCann  7 , Jerome D Winegarden  8 , Mohammed A Kassem  9 , Mohamed K Mohamed  10 , Jan M Rothman  11 , Alan P Lyss  12 , Leora Horn  13 , Thomas E Stinchcombe  14 , Joan H Schiller  15
Affiliations
Randomized Controlled Trial

Pemetrexed, Bevacizumab, or the Combination As Maintenance Therapy for Advanced Nonsquamous Non-Small-Cell Lung Cancer: ECOG-ACRIN 5508

Suresh S Ramalingam et al. J Clin Oncol. .

Abstract

Purpose: Pemetrexed or bevacizumab is used for maintenance therapy of advanced nonsquamous non-small-cell lung cancer (NSCLC). The combination of bevacizumab and pemetrexed has also demonstrated efficacy. We conducted a randomized study to determine the optimal maintenance therapy.

Patients and methods: Patients with advanced nonsquamous NSCLC and no prior systemic therapy received carboplatin (area under the curve, 6), paclitaxel (200 mg/m2), and bevacizumab (15 mg/kg) for up to four cycles. Patients without progression after four cycles were randomly assigned to maintenance therapy with bevacizumab (15 mg/kg), pemetrexed (500 mg/m2), or a combination of the two agents. The primary end point was overall survival, with bevacizumab serving as the control group.

Results: Of the 1,516 patients enrolled, 874 (57%) were randomly assigned after induction therapy to one of the three maintenance therapy groups. With a median follow-up of 50.6 months, median survival with pemetrexed was 15.9 months, compared with 14.4 months with bevacizumab (hazard ratio [HR], 0.86; P = .12); median survival with pemetrexed and bevacizumab was 16.4 months (HR, 0.9; P = .28); median progression-free survival was 4.2, 5.1 (HR, 0.85; P = .06), and 7.5 months (HR, 0.67; P < .001) for the three groups, respectively. Incidence of worst grade 3 to 4 toxicity was 29%, 37%, and 51%, respectively, for bevacizumab, pemetrexed, and the combination regimen.

Conclusion: Single-agent bevacizumab or pemetrexed is efficacious as maintenance therapy for advanced nonsquamous NSCLC. Because of a lack of survival benefit and higher toxicity, the combination of bevacizumab and pemetrexed cannot be recommended.

Trial registration: ClinicalTrials.gov NCT01107626.

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Conflict of interest statement

The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health, nor does mention of trade names, commercial products, or organizations imply endorsement by the US government.

Figures

FIG 1.
FIG 1.
CONSORT diagram.
FIG 2.
FIG 2.
Kaplan-Meier curve for overall survival (OS). HR, hazard ratio.
FIG 3.
FIG 3.
Kaplan-Meier curve for progression-free survival (PFS). HR, hazard ratio.
See this image and copyright information in PMC

Comment in

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