PointBreak: A Randomized Phase III Study of Pemetrexed Plus Carboplatin and Bevacizumab Followed by Maintenance Pemetrexed and Bevacizumab Versus Paclitaxel Plus Carboplatin and Bevacizumab Followed by Maintenance Bevacizumab in Patients With Stage IIIB or IV Nonsquamous Non–Small-Cell Lung Cancer

Abstract

A B S T R A C T PurposePointBreak (A Study of Pemetrexed, Carboplatin and Bevacizumab in Patients With Nonsquamous Non-Small Cell Lung Cancer) compared the efficacy and safety of pemetrexed (Pem) plus carboplatin (C) plus bevacizumab (Bev) followed by pemetrexed plus bevacizumab (PemCBev) with paclitaxel (Pac) plus carboplatin (C) plus bevacizumab (Bev) followed by bevacizumab (PacCBev) in patients with advanced nonsquamous non-small-cell lung cancer (NSCLC). Patients and MethodsPatients with previously untreated stage IIIB or IV nonsquamous NSCLC and Eastern Cooperative Oncology Group performance status of 0 to 1 were randomly assigned to receive pemetrexed 500 mg/m 2 or paclitaxel 200 mg/m 2 combined with carboplatin area under the curve 6 and bevacizumab 15 mg/kg every 3 weeks for up to four cycles. Eligible patients received maintenance until disease progression: pemetrexed plus bevacizumab (for the PemCBev group) or bevacizumab (for the PacCBev group). The primary end point of this superiority study was overall survival (OS). ResultsPatients were randomly assigned to PemCBev (n ϭ 472) or PacCBev (n ϭ 467). For PemCBev versus PacCBev, OS hazard ratio (HR) was 1.00 (median OS, 12.6 v 13.4 months; P ϭ .949); progression-free survival (PFS) HR was 0.83 (median PFS, 6.0 v 5.6 months; P ϭ .012); overall response rate was 34.1% versus 33.0%; and disease control rate was 65.9% versus 69.8%. Significantly more study drug-related grade 3 or 4 anemia (14.5% v 2.7%), thrombocytopenia (23.3% v 5.6%), and fatigue (10.9% v 5.0%) occurred with PemCBev; significantly more grade 3 or 4 neutropenia (40.6% v 25.8%), febrile neutropenia (4.1% v 1.4%), sensory neuropathy (4.1% v 0%), and alopecia (grade 1 or 2; 36.8% v 6.6%) occurred with PacCBev. ConclusionOS did not improve with the PemCBev regimen compared with the PacCBev regimen, although PFS was significantly improved with PemCBev. Toxicity profiles differed; both regimens demonstrated tolerability.

Efficacy and safety of maintenance pemetrexed in patients with advanced nonsquamous non-small cell lung cancer following pemetrexed plus cisplatin induction treatment: A cross-trial comparison of two phase III trials

“…The higher proportion of patients in the JMDB homogenized population with "Other" or "Indeterminate" histology could be due to a higher proportion of cytological diagnosis, although recent studies enrolled a similar percentage of patients with Other/Indeterminate histology as in JMDB [19] and [20]. For the JMDB homogeneous population, a higher percentage of patients with Other/Indeterminate histology might imply some prognostic disadvantage, while a greater percentage of patients with disease stage IIIb might have provided a prognostic advantage.…”

Improved tumor vascularization after anti-VEGF therapy with carboplatin and nab-paclitaxel associates with survival in lung cancer

“…Bevacizumab with carboplatin and paclitaxel chemotherapy is a standard first-line treatment of nonsquamous NSCLC based on the Eastern Cooperative Oncology Group (ECOG) 4599 trial (1). Efforts to improve on the outcomes have included combining bevacizumab with other agents, including carboplatin and pemetrexed (12), among others, but thus far, no regimen has shown clear superiority. In this single institution phase II study, the combination of bevacizumab with carboplatin and nab-paclitaxel was well tolerated, with a promising PR rate of 36% and a 6-mo PFS rate of 74%, with a median PFS of 8.5 mo and OS of 12.2 mo.…”

Nivolumab Monotherapy for First-Line Treatment of Advanced Non–Small-Cell Lung Cancer

“…[1][2][3][4][5][6] Addition of bevacizumab to firstline PT-DC modestly improves clinical outcome versus chemotherapy alone in patients with nonsquamous NSCLC (ORR,33% to 35%;median OS,12.3 to 13.4 months; and 1-year OS rate, 51% to 54.1%). 3,7 In the small subset of patients with advanced NSCLC driven by EGFR or ALK genomic alterations, first-line therapy with EGFR or ALK tyrosine kinase inhibitors (TKIs), respectively, has consistently demonstrated higher ORRs (56% to 83%) and longer PFS (median, 9.2 to 13.1 months) with less toxicity than first-line PT-DC. [8][9][10][11][12][13] Immune checkpoint inhibitors represent a distinct approach to treating malignancies, with durable antitumor activity and the potential for long-term survival demonstrated in multiple tumor types, including NSCLC.…”