A Randomized Phase II Trial of Pemetrexed/Gemcitabine/Bevacizumab or Pemetrexed/Carboplatin/Bevacizumab in the First-Line Treatment of Elderly Patients with Advanced Non-small Cell Lung Cancer

Purpose: To assess time to progression (TTP) in elderly patients with previously untreated nonsquamous non-small cell lung cancer treated with pemetrexed/gemcitabine/bevacizumab or pemetrexed/carboplatin/bevacizumab. Methods: Eligible patients were aged 70 years or older with newly diagnosed stage IIIB/IV nonsquamous non-small cell lung cancer; Eastern Cooperative Oncology Group performance status 0 to 1; adequate organ function; and no active central nervous system metastasis. Patients were randomized 1: 1 to cohort A (pemetrexed 500 mg/m(2) IV, gemcitabine 1500 mg/m2 IV, and bevacizumab 10 mg/kg IV; days 1 and 15 of 28-day cycles) or cohort B (pemetrexed 500 mg/m2 IV, carboplatin area under the concentration-time curve = 5 IV, and bevacizumab 15 mg/kg IV; day 1 of 21-day cycles). After six cycles, stable/responding patients continued bevacizumab until disease progression. Results: Between March 2007 and December 2009, 110 patients (median age, 76 years; 88% stage IV) were treated for medians of 2.5 cycles (cohort A) and 6 cycles (cohort B). Overall response rate was 35% in both cohorts, with stable disease rates of 33% (A) and 45% (B). TTP by cohort was 4.7 and 10.2 months with median OS 7.5 and 14.8 months, respectively. Severe toxicities included the following: neutropenia (A, 51% and B, 45%), fatigue (A, 36% and B, 18%), anemia (A, 22% and B, 7%), infection (A, 25% and B, 7%), thrombocytopenia (A, 11% and B, 31%), and thromboembolism (A, 7% and B, 7%). Three potential treatment-related deaths occurred in cohort A (sepsis, thrombocytopenia, and myocardial infarction) and two in B (sepsis and pulmonary hemorrhage). Conclusions: Treatment with pemetrexed/carboplatin/bevacizumab was associated with improved TTP and OS in this elderly population and should be further evaluated. Treatment-related toxicities were expected and usually manageable, although deaths occurred with both regimens.