Pemetrexed plus platinum-based chemotherapy has emerged as an effective combination in patients with nonsquamous non-small-cell lung cancer (NSCLC). However, the efficacy of this combination in elderly patients (≥75 years of age) with advanced-stage disease remains unknown. Now, data from a phase III trial demonstrate the efficacy of pemetrexed plus cisplatin in this setting.
A total of 433 elderly patients with chemotherapy-naive advanced-stage nonsquamous NSCLC (stage IV disease, or stage III and not amenable to radiotherapy) were randomly assigned (1:1) to receive carboplatin plus pemetrexed followed by maintenance pemetrexed versus docetaxel monotherapy. Overall survival (OS) was the primary end point of this study.
At a median follow-up duration of 17.1 months, patients in the carboplatin plus pemetrexed group had a median OS of 18.7 months versus 15.5 months (stratified HR 0.85, 95% CI 0.68–1.06; Pnoninferiority = 0.003). Progression-free survival (PFS) outcomes also favoured carboplatin plus pemetrexed: median 6.4 months versus 4.3 months (unstratified HR 0.74, 95% CI 0.61–0.9; P <0.001).
More patients in the docetaxel group discontinued therapy owing to tolerability (13.6% versus 9.8%), although type of events varied: patients receiving docetaxel were more likely to have grade 3–4 neutropenia (86.0% versus 46.3%), white blood cell count (68.7% versus 28.0%) and febrile neutropenia (17.8% versus 4.2%), while those receiving carboplatin plus pemetrexed were more likely to have grade 3–4 anaemia (29.4% versus 1.9%) and reductions in platelet count (25.7% versus 1.4%).
These data demonstrate the noninferiority of carboplatin plus pemetrexed in elderly patients with nonsquamous NSCLC. No significant improvement in OS was observed, although secondary end points support the use of carboplatin plus pemetrexed.
Okamoto, I. 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. JAMA Oncol. https://doi.org/10.1001/jamaoncol.2019.6828 (2020)
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Sidaway, P. Doublet therapy effective in elderly patients. Nat Rev Clin Oncol 17, 337 (2020). https://doi.org/10.1038/s41571-020-0360-8