Pemetrexed Continuation Maintenance Phase 3 Trials in Nonsquamous, Non-Small-Cell Lung Cancer: Focus on 2-Year Overall Survival and Continuum of Care.

Although lung cancer prognosis remains poor for most patients, treatments developed in the past 2 decades have extended survival for many. For those with disease that responded to or those with stable disease after receipt of platinum-based chemotherapy, maintenance regimens enable continued targeting of tumors beyond the induction phase, which is limited by toxicity. This overview summarizes completed phase 3 trials of pemetrexed continuation maintenance treatment in nonsquamous, non-small-cell lung cancer with a focus on 2-year survival, and highlights similar ongoing trials. Some studies showed survival benefits of pemetrexed maintenance treatment versus control arms, with the potential for added benefit when combined with bevacizumab. Two-year survival rates underscore the value of maintenance therapy and suggest progress toward a clinical goal of managing non-small-cell lung cancer as a treatable chronic disease.

PRONOUNCE: randomized, open-label, phase III study of first-line pemetrexed + carboplatin followed by maintenance pemetrexed versus paclitaxel + carboplatin + bevacizumab followed by maintenance bevacizumab in patients ith advanced nonsquamous non-small-cell lung cancer.

INTRODUCTION: PRONOUNCE compared the efficacy and safety of pemetrexed+carboplatin followed by pemetrexed (Pem+Cb) with paclitaxel+carboplatin+bevacizumab followed by bevacizumab (Pac+Cb+Bev) in patients with advanced nonsquamous non-small-cell lung cancer (NSCLC). METHODS: Patients ≥18 years of age with stage IV nonsquamous NSCLC (American Joint Committee on Cancer v7.0), and Eastern Cooperative Oncology Group performance status 0/1 were randomized (1:1) to four cycles of induction Pem+Cb (pemetrexed, 500 mg/m, carboplatin, area under the curve = 6) followed by Pem maintenance or Pac+Cb+Bev (paclitaxel, 200 mg/m, carboplatin, area under the curve = 6, and bevacizumab, 15 mg/kg) followed by Bev maintenance in the absence of progressive disease or discontinuation. The primary objective was progression-free survival (PFS) without grade 4 toxicity (G4PFS). Secondary end points were PFS, overall survival (OS), overall response rate (ORR), disease control rate (DCR), and safety. Resource utilization was also assessed. RESULTS: Baseline characteristics of the patients randomized to Pem+Cb (N = 182) and Pac+Cb+Bev (N = 179) were well balanced between the arms. Median (months) G4PFS was 3.91 for Pem+Cb and 2.86 for Pac+Cb+Bev (hazard ratio = 0.85, 90% confidence interval, 0.7-1.04; p = 0.176); PFS, OS, ORR, or DCR did not differ significantly between the arms. Significantly more drug-related grade 3/4 anemia (18.7% versus 5.4%) and thrombocytopenia (24.0% versus 9.6%) were reported for Pem+Cb. Significantly more grade 3/4 neutropenia (48.8% versus 24.6%), grade 1/2 alopecia (28.3% versus 8.2%), and grade 1/2 sensory neuropathy were reported for Pac+Cb+Bev. Number of hospitalizations and overall length of stay did not differ significantly between the arms. CONCLUSIONS: Pem+Cb did not produce significantly better G4PFS compared with Pac+Cb+Bev. Pem+Cb was not superior in PFS, OS, ORR, or DCR compared with Pac+Cb+Bev. Both regimens were well tolerated, although, toxicity profiles differed.