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

• Type of Material: Article
• Authors: Suresh Ramalingam, Emory University; Suzanne E. Dahlberg, Dana Farber Cancer Institute; Chandra P. Belani, Penn State Health Milton S. Hershey Medical Center, Hershey, PA; Joel N. Saltzman, University Hospitals Seidman Cancer Center, Cleveland, OH; Nathan A. Pennell, Cleveland Clinic; Gopakumar S. Nambudiri, St. John Hospital & Medical Center; John C. McCann, Baystate Health; Jerome D. Winegarden, St Joseph Mercy Ann Arbor Hospital; Mohammed A. Kassem, Sinai Cancer Care and Infusion Center, Chicago, IL; Mohammed K. Mohamed, Moses H. Cone Memorial Hospital; Jan M. Rothman, University of Pittsburgh; Alan P. Lyss, Missouri Baptist Medical Center; Leora Horn, Vanderbilt University; Thomas E. Stinchcombe, Duke University; Joan H. Schiller, Inova Schar Cancer Center, VA
• Language: English
• Date: 2019-09-10
• Publisher: American Society of Clinical Oncology
• Publication Version: Final Published Version
• Copyright Statement: © 2021 American Society of Clinical Oncology. All rights reserved.
• Final Published Version (URL): http://dx.doi.org/10.1200/JCO.19.01006
• Title of Journal or Parent Work: Journal of Clinical Oncology
• Volume: 37
• Issue: 26
• Start Page: 2360
• End Page: 2368
• Grant/Funding Information: Supported by National Cancer Institute Awards No. CA180820, CA180794, CA180821, CA180838, CA180844, CA180847, CA180853, CA180857, CA180864, CA180867, CA180868, CA180870, CA180882, CA189830, CA189859, CA189863, and CA189971.
• Keywords: Plus; Cisplatin; Paclitaxel; 1st line therapy; Carboplatin; Randomized phase II; Enhance; Oncology; Science & Technology; Tumor; Life Sciences & Biomedicine
• Research Categories: Biology, Genetics; Health Sciences, Rehabilitation and Therapy; Biology, Cell; Health Sciences, Oncology

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.