Retrospective evaluation of chemotherapy options in non-squamous non-small cell lung cancer (non-Sq NSCLC) patients (pts) unfit for standard platinum-based chemotherapy in clinical practice

Abstract

Background: In clinical practice, major challenge in non-Sq NSCLC pts unfit for standard platinum-based chemotherapy, due to age and/or comorbidities, is the selection between mono- or doublet-chemotherapy properly weighing expected clinical outcome and safety profile in the individual patient. Patients and methods: Consecutive pts EGFR wild-type and mutant unsuitable for anti-EGFR were treated in clinical practice. Conventional or modified (schedules and/ or dosage of doublets, or mono-chemotherapy) first-lines were selected according to fitness, defined by age (non-elderly, young-elderly YE ≥65 < 75 y, old-elderly OE ≥75 y), performance status (PS), and comorbidity (Cumulative Illness Rating Scale). Activity and efficacy were evaluated, and compared by log-rank. Limiting toxicity syndromes (LTS) were used to evaluate individual safety. Results: From November 2009 to February 2015, 45 pts were treated: 21 fit (46.6%) with conventional and 24 (53.4%) unfit with modified regimens; specifically 14 (31.1%) fit standard platinum/pemetrexed (sPP) and 10 (22.2%) unfit modified PP (mPP). Unfit were prevalently YE/OE, PS 1-2, CIRS secondary. Overall, objective response rate (ORR), progression-free survival (PFS), overall survival (OS) were 47.7%, 7 and 13 months. Among fit and unfit, respectively: 61.1% and 30%, 8 and 6 months (p 0.935), 15 and 13 months (p 0.963). Among all PP, 60%, 8 and 15 months. Among sPP and mPP, respectively: 66.6% and 50%, 5 and 8 months (p 0.247), 15 and 13 months (p 0.816). In PP pts, no significantly different cumulative toxicities were reported among sPP and mPP; LTS were 6 (25%): only 1 (4.1%) single-site (LTS-SS) in fit, all 5 (20.8%) multiple-site (LTS-MS) in unfit, with cardiovascular comorbidities, and represented by neutropenia, thrombocytopenia, asthenia, hypertransaminasemia, hypoalbuminemia, atrial fibrillation, and arrhythmia. In mPP received dose-intensities (rDIs) were ?80% of projected standard doses. Overall, among unfit pts, 12 (26.6%) were treated with modified platinum-based doublets and 12 (26.6%), prevalently OE, with mono-chemotherapy; ORR, PFS and OS were: 50% and 10%, 8 and 3 months (p 0.008), 15 and 13 months (p 0.360), respectively. Conclusions: mPP schedules (rDIs ≥80%) may be a therapeutic option for unfit pts, due to not significantly different efficacy and cumulative toxicity compared to sPP, but individual unfit pts prevalently show LTS-ms. Unfit pts treated with mono-chemotherapy show significantly worse PFS.