Exploratory analysis of JFCM: Predictive value of rash, EGFR expression, and EGFR copy for necitumumab in squamous NSCLC

Background: JFCM, an open-label, multicenter, phase 1b/2 study (n = 181), demonstrated that addition of necitumumab (N) to gemcitabine and cisplatin (GC) resulted in significant improvement in overall survival (OS; hazard ratio [HR] = 0.66) in the first-line treatment of advanced squamous non-small cell lung cancer (NSCLC) patients in Japan. Previous studies have suggested that rash, EGFR expression, and EGFR copy number gain might be associated with the efficacy of EGFR-targeting drugs in the treatment of squamous NSCLC. Methods: Our analysis assessed: development of acne-like rash in the first cycle; EGFR expression (evaluated by H-score of immunohistochemistry, H ≥ 200 vs H < 200); and EGFR copy number gain of tumor cells (evaluated by fluorescence in situ hybridization [FISH]; positive vs negative) for association with clinical outcome in JFCM study. Results: Of the 90 patients in the GC+N arm, 80 (88.9%) had first-cycle rash. Median OS was 14.52 vs 15.93 months (HR = 1.39) in patients experiencing first-cycle rash vs those without rash in the GC+N arm. For EGFR expression, the majority of patients had H < 200 in both arms (H < 200: GC+N=74, GC = 65; H ≥ 200: GC+N=13, GC = 23). The efficacy outcome did not vary significantly with EGFR expression with median OS of 14.92 and 10.28 months (HR = 0.643) in the H < 200 subgroup, and 14.00 and 10.28 months (HR = 0.580) in H ≥ 200 subgroup, for GC+N and GC arms respectively. For EGFR copy number, 29 vs 37 cases were FISH positive while 38 vs 32 cases were FISH negative in the GC+N vs GC arms, respectively. In FISH positive patients, median OS was 14.00 and 9.43 months (HR = 0.73) while median OS in FISH negative patients was 15.70 and 12.02 months (HR = 0.65) in GC+N vs GC arms, respectively. Conclusion: Our analysis did not identify first-cycle rash, EGFR expression, and EGFR copy number gain as predictive markers of survival in JFCM study. (Trial Registration Number: NCT01763788)