‘Biology-driven’ adjuvant treatment selection is feasible for NSCLC
medwireNews: French phase II study results indicate that selecting patients with non-small-cell lung cancer (NSCLC) for post-surgery chemotherapy according to the presence of certain biomarkers is a feasible approach.
Complete biomarker status was achieved before day 61 after surgery in 80% of study participants, comprising 77% of those in a standard treatment group and 83% in a customised treatment group, report Marie Wislez (Hôpital Tenon, Assistance Publique des Hôpitaux de Paris) and colleagues. This demonstrates the feasibility of a “national biology-driven approach” to adjuvant treatment of NSCLC.
However, the reliability of some of the immunohistochemical readouts in the study was questionable compared with previous studies, remark the researchers in the Journal of Clinical Oncology, leading to the cancellation of their planned phase III trial.
The research team randomly assigned 150 patients to undergo either standard (n=74; cisplatin 75 mg/m2 plus pemetrexed 500 mg/m2 [CP]) or customised (n=76; CP alone, CP plus erloinib or exclusive follow-up) chemotherapy schedules within 2 months of surgery. The type of customised treatment depended on epidermal growth factor receptor (EGFR) mutation and excision repair cross-complementation group 1 (ERCC1) status.
Among those in the customised treatment group, seven patients with activating EGFR mutations – a known predictor of erlotinib responsiveness – received it orally at 150 mg per day. All bar two of the 53 patients with negative ERCC1 status received at least one standard dose course of CP, and the remaining 16 patients with positive ERCC1 status, previously linked to platinum resistance, were followed up exclusively.
CP had an “excellent” tolerability profile, they add, with 82% of patients receiving four standard CP cycles and no grade 5 Common Terminology Criteria for Adverse Events reported. The most common grade 1 and 2 adverse events were asthenia and anaemia, at 66% and 63%, respectively, while the most common grade 3 and 4 event was neutropenia, reported by 32% of patients.
However, Wislez and team observed significant differences in ERCC1 expression status (60% of patients had no expression and 25% were positive) among the cohort compared with that reported by the International Adjuvant Lung Cancer Trial (IALT). Specifically, there were “clear discrepancies” between the 8F1 antibody batches as well as further differences when comparing IALT biosamples gathered in 2006 and 2011.
“This observation led us to the conclusion that ERCC1 [immunohistochemistry] readouts were suboptimal”, remark Wislez et al, who suggest that the methodology requires improvement.
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By Sarah Pritchard, medwireNews Reporter