Open-label, multicenter, randomized phase III trial of pemetrexed/carboplatin doublet vs pemetrexed singlet in chemotherapy-naïve elderly patients aged 70 or more with advanced non-squamous non–small-cell lung cancer and good performance status

Conference Correspondent - ASCO 2016


Age and related comorbidities often reduce the therapeutic index of drugs; however, there is no evidence in favor of selecting chemotherapy based on age. Lee and colleagues compared the pemetrexed/carboplatin (PC) doublet versus pemetrexed singlet in chemotherapy-naïve elderly patients aged 70 years or older with advanced nonsquamous non–small-cell lung cancer (NSCLC) and an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1.1 In this open-label, multicenter phase 3, randomized trial, elderly patients aged 70 years or older with advanced nonsquamous NSCLC; ECOG PS of 0-1; adequate hematologic, hepatic, and renal function; no prior chemotherapy; and histologically or cytologically confirmed disease were assigned to PC doublet (pemetrexed, 500 mg/m2; carboplatin, area under the curve of 5) or pemetrexed singlet (500 mg/m2) after stratified randomization according to sex and Charlson Comorbidity Index (CCI). The treatment was given every 3 weeks until disease progression, unacceptable toxicity, or withdrawal of consent. However, carboplatin was given only for the first 4 cycles. Maintenance therapy with pemetrexed alone was allowed after 4 cycles of induction therapy. The primary end point was progression-free survival (PFS). Secondary end points included overall survival (OS), response rate, and safety. A total of 267 eligible patients were enrolled; the median age was 74 years (range, 70-86); 95% had a PS of 1; 65% were men; and 63% had a CCI of ≥1. The median PFS was 5.4 months for patients receiving the PC doublet and 4.2 months for those treated with the pemetrexed singlet (hazard ratio [HR], 0.85; 95% confidence interval [CI], 0.65-1.11; P = 0.253). The median OS was 12.5 months for PC and 9.0 months for pemetrexed (HR, 0.86; 95% CI, 0.62-1.21; P = 0.4108). Overall response rates between the 2 groups were not significantly different (35% vs 26%; P = 0.1387). Grade 3/4 toxicity was seen more frequently in patients receiving PC than in those treated with pemetrexed alone, especially with respect to anemia, fatigue, and diarrhea. The authors concluded that addition of carboplatin to pemetrexed did not show the improvement of survival time in elderly patients aged 70 years or older with advanced nonsquamous NSCLC and ECOG PS of 0-1, and that pemetrexed alone was effective in this patient population.
  1. Lee DH, et al. ASCO 2016. Abstract 9081.