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

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.

Clinical Option of Pemetrexed-Based Versus Paclitaxel-Based First-Line Chemotherapeutic Regimens in Combination With Bevacizumab for Advanced Non-Squamous Non-Small-Cell Lung Cancer and Optimal Maintenance Therapy: Evidence From a Meta-Analysis of Randomized Control Trials

“…Even though Pem + B showed signi cant bene ts in PFS compared to monotherapy B maintenance, four previous studies did not recommend Pem + B as a standard maintenance regimen because of the lack of OS bene ts and higher toxicity [9,11,12,14]. Combining two recent RCTs [11,12], our metaanalysis showed not only an improvement in PFS with Pem + B maintenance, but also a bene t in OS (P = 0.05). The PointBreak study showed a longer OS for Pem + B maintenance than B alone, but that trial could not be included in our meta-analysis, because the timepoint after random assignment was different from those in the other trials [14].…”

“…For NS-NSCLC patients, Pem + B in combination or as a single drug as a maintenance therapy is shown to be bene cial for survival [9,10,14,23]. Even though Pem + B showed signi cant bene ts in PFS compared to monotherapy B maintenance, four previous studies did not recommend Pem + B as a standard maintenance regimen because of the lack of OS bene ts and higher toxicity [9,11,12,14]. Combining two recent RCTs [11,12], our metaanalysis showed not only an improvement in PFS with Pem + B maintenance, but also a bene t in OS (P = 0.05).…”

“…Based on the inclusion and exclusion criteria, six RCTs [9,11,12,[14][15][16], including 3,144 NS-NSCLC patients were included in this meta-analysis. The baseline characteristics of the included studies are in Tables 1 and 2.…”

“…Among them, three trials [14][15][16] were included in analysis comparing rst-line treatment regimens between PP±B and PC+B. Three other trials [9,11,12] were included for analysis to compare maintenance regimens between Pem+B and B. The ow diagram of the literature retrieval and selection is in Figure 1.…”

“…Three RCTs including 1,726 patients were used to compare the e cacy and safety of Pem+B and B maintenance [9,11,12]. Two RCTs used a continuation maintenance regimen in the study design [9,11], and one study used continuation and switch maintenance regimens [12]. Indirect comparisons between Pem+B versus Pem maintenance and between Pem versus B maintenance were also analyzed.…”