Practice Patterns and Outcomes for Pemetrexed Plus Platinum Doublet as Neoadjuvant Chemotherapy in Adenocarcinomas of Lung: Looking Beyond the Usual Paradigm

Abstract

Aims: Neoadjuvant chemotherapy (NACT) is the standard of care in non-small cell lung cancers (NSCLC) with locally advanced N2 disease. There is a scarcity of data for the pemetrexed-platinum regimen as NACT. Also, apart from N2 disease, the role of NACT in locally advanced NSCLCs for tumour downstaging is unclear.

Materials and methods: Non-metastatic adenocarcinomas of lung treated with pemetrexed-platinum-based NACT were analysed. The patients with locoregionally advanced N2 disease and those who were borderline candidates for upfront definitive treatment were planned for NACT after discussion in a multidisciplinary clinic. In total, four cycles of 3-weekly pemetrexed and platinum were delivered in the combined neoadjuvant and adjuvant setting. A response assessment was carried out using RECIST criteria. Progression-free (PFS) and overall survival were calculated using the Kaplan-Meier method.

Results: Of 114 patients, 96 evaluable patients received NACT with pemetrexed-platinum. The most common indication for NACT was N2 disease at baseline (46.8%). The objective response rate was 36.4% (95% confidence interval 22-52%), including two complete and 32 partial responses, whereas 12.5% of patients had progressive disease on NACT. The median PFS was 14 months (95% confidence interval 10.7-17.3) and the median overall survival was 22 months (95% confidence interval 15.6-28.4) at a median follow-up of 16 months. There was a significant improvement in the overall survival of patients undergoing definitive therapy versus no definitive therapy (median overall survival 25 months [95% confidence interval 19.6-30.4] versus 12 months [95% confidence interval 3.2-20.7], respectively; P = 0.015, hazard ratio 0.56 [95% confidence interval 0.3-0.9]). Among patients who could not undergo definitive chemoradiation upfront due to dosimetric constraints (n = 34), 24 (70.6%) patients finally underwent definitive therapy after NACT.

Conclusions: Pemetrexed-platinum-based NACT seems to be an effective option and many borderline cases, where upfront definitive therapy is not feasible, may become amenable to the same after incorporation of NACT.

Keywords: Non-metastatic adenocarcinoma lung; pemetrexed neoadjuvant chemotherapy.