Is treatment with carboplatin plus pemetrexed followed by pemetrexed maintenance noninferior compared with docetaxel monotherapy with regard to overall survival for elderly patients with advanced nonsquamous non–small cell lung cancer (NSCLC)?
This phase 3 randomized clinical trial including 433 elderly patients with a median age of 78 years met its primary end point and demonstrated noninferiority of carboplatin-pemetrexed treatment followed by pemetrexed maintenance compared with docetaxel monotherapy in terms of overall survival for chemotherapy-naive elderly patients with advanced nonsquamous NSCLC.
The combination of carboplatin and pemetrexed followed by pemetrexed maintenance is a valid option for first-line treatment of elderly patients with advanced nonsquamous NSCLC.
Few clinical trials have been specifically designed for elderly patients with advanced non–small cell lung cancer (NSCLC), and the anticipated increase in the number of such patients has prompted a search for new treatment options that provide a greater palliative benefit.
To determine whether treatment with carboplatin plus pemetrexed followed by pemetrexed maintenance is noninferior compared with docetaxel monotherapy with regard to overall survival (OS) for elderly patients with advanced nonsquamous NSCLC.
Design, Setting, and Participants
This open-label, multicenter, noninferiority phase 3 randomized clinical trial was conducted at 79 institutions in Japan. Cytotoxic chemotherapy–naive patients with advanced nonsquamous NSCLC, an Eastern Cooperative Oncology Group performance status of 0 or 1, and age of 75 years or older were enrolled between August 2013 and February 2017. Data were analyzed from November 2018 to February 2019.
Patients were randomized to receive either docetaxel monotherapy (60 mg/m2) every 3 weeks or 4 cycles of carboplatin (area under the curve of 5) plus pemetrexed (500 mg/m2) administered every 3 weeks followed by maintenance therapy with the same dose of pemetrexed for 3 weeks.
Main Outcomes and Measures
The primary end point was OS analyzed on an intention-to-treat basis with a noninferiority margin of 1.154 for the upper limit of the 95% CI of the hazard ratio (HR) estimated with a stratified Cox regression model.
Of the 433 enrolled patients, 250 (57.7%) were male, and the median (range) age was 78 (75-88) years. The median OS was 15.5 months (95% CI, 13.6-18.4) in the docetaxel group (n = 217) and 18.7 months (95% CI, 16.0-21.9) in the carboplatin-pemetrexed group (n = 216), with a stratified HR for OS of 0.850 (95% CI, 0.684-1.056; P for noninferiority = .003). Progression-free survival was also longer in the carboplatin-pemetrexed group (unstratified HR, 0.739; 95% CI, 0.609-0.896). Compared with those in the docetaxel group, those in the carboplatin-pemetrexed had lower rates of leukopenia (60 of 214 [28.0%] vs 147 of 214 [68.7%]) and neutropenia (99 of 214 [46.3%] vs 184 of 214 [86.0%]) of grade 3 or 4 and of febrile neutropenia (9 of 214 [4.2%] vs 38 of 214 [17.8%]) and higher rates of thrombocytopenia (55 of 214 [25.7%] vs 3 of 214 [1.4%]) and anemia (63 of 214 [29.4%] vs 4 of 214 [1.9%]) of grade 3 or 4. Dose reductions were less frequent with carboplatin-pemetrexed.
Conclusion and Relevance
Carboplatin-pemetrexed treatment followed by pemetrexed maintenance is a valid option for first-line treatment of elderly patients with advanced nonsquamous NSCLC.
University Hospital Medical Information Network Clinical Trials Registry Identifier: UMIN000011460
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Okamoto I, Nokihara H, Nomura S, et al. Comparison of Carboplatin Plus Pemetrexed Followed by Maintenance Pemetrexed With Docetaxel Monotherapy in Elderly Patients With Advanced Nonsquamous Non–Small Cell Lung Cancer: A Phase 3 Randomized Clinical Trial. JAMA Oncol. Published online March 12, 2020. doi:10.1001/jamaoncol.2019.6828
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