Differential efficacy of cisplatin plus pemetrexed between L858R and Del-19 in advanced EGFR-mutant non-squamous non-small cell lung cancer

Background

Combined analysis from two randomized phase 3 trials showed afatinib improved overall survival (OS) compared with platinum doublets in patients with Exon 19 deletion (Del-19) mutation. However, in patients with Leu858Arg (L858R) point mutation, afatinib efficacy did not differ significantly from chemotherapy. We hypothesized that this discrepancy was due to differential efficacy of cisplatin plus pemetrexed between Del-19 and L858R.

Methods

This study is a multicenter retrospective study. We reviewed medical records of patients who had received cisplatin plus pemetrexed as first line chemotherapy. Efficacies were evaluated among epidermal growth factor receptor (EGFR) mutation status: Del-19; L858R; and wild type.

Results

Among 304 patients, 78 (25.7%) harbored EGFR mutations: Del-19 (36/78 patients, 46.2%); and L858R (42/78, 53.8%). Median PFS of L858R group (9.4 months, 95% confidence interval [CI]: 7.0-12.6) was significantly longer than Del-19 group (5.5 months, 95% CI: 3.6-8.6) (p = 0.049). Response rate (RR) and OS presented no significant difference among L858R, Del-19 or wild type. In multivariate analysis, EGFR mutation status (L858R versus Del-19) was the only significant factor for longer PFS (Hazard ratio [HR]: 0.78, 95% CI: 0.62-0.98) (p = 0.033).

Conclusions

Our study indicated better efficacy of cisplatin plus pemetrexed in L858R than in Del-19 patients. This result could be a valuable suggestion to consider better therapeutic strategies for L858R patients.

Clinical trial identification

none

Legal entity responsible for the study

Kurashiki Central Hospital

Funding

Kurashiki Central Hospital

Disclosure

H. Yoshioka: Hiroshige Yoshioka received lecture fees from Chugai, Astra Zeneca, Boehringer Ingelheim, and Eli Lilly. A. Hata: Akito Hata received lecture fees from Chugai, Astra Zeneca, Boehringer Ingelheim, and Eli Lilly. N. Katakami: Nobuyuki Katakami received grants from Astra Zeneca, Chugai, Eli Lilly, and Boehringer Ingelheim, and payment for lectures from Chugai, Boehringer Ingelheim, Astra Zeneca, and Eli Lilly. All other authors have declared no conflicts of interest.