Survival outcomes and subgroup analyses derived from a phase III randomized trial comparing afatinib to chemotherapy in treatment-naïve non-small cell lung cancer with a sensitizing uncommon epidermal growth factor receptor mutation (ACHILLES/TORG1834).

<jats:p> 8588 </jats:p><jats:p> Background: The ACHILLES/TORG1834 trial is the first randomized phase 3 study, demonstrating the superiority of afatinib to chemotherapy in terms of progression-free survival (PFS) as a primary endpoint in sensitizing uncommon epidermal growth factor receptor (EGFR) mutant non-small cell lung cancer (NSCLC) (the hazard ratio [HR] of PFS was 0.422, p=0.0007). This trial was early terminated due to efficacy according to the recommendation by the data and safety monitoring committee. Here we report the overall survival (OS) result, subgroup analysis of PFS, and the response data according to detailed mutation status at the primary analysis. Methods: In this open-label phase III study, treatment-naïve patients (n=109) with sensitizing uncommon EGFR mutant NSCLC were randomized 2:1 to oral afatinib (30 mg or 40 mg daily) or the combination of platinum (cisplatin 75 mg/m<jats:sup>2</jats:sup> or carboplatin AUC 5 or 6) and pemetrexed (500 mg/m<jats:sup>2</jats:sup>), followed by pemetrexed maintenance therapy every 3 weeks. The primary endpoint was PFS per RECIST 1.1. The secondary endpoints included objective response rate (ORR), time to treatment failure (TTF), and OS. Results: Median follow-up time was 12.5 (range, 0 to 43.5) months. The OS HR of afatinib compared to chemotherapy was 0.989 (95% confidence interval [CI], 0.457 to 2.141; p=0.9772; 29/109 events, 26.6% maturity). Median OS was not reached in either population. All subgroups of PFS did better in the afatinib arm. In the subgroup regarding the starting dose of afatinib, the PFS HR in the 40mg afatinib arm (HR 0.128, 95%CI, 0.050 to 0.327) were favorable compared to that in the 30mg afatinib arm (HR 0.704, 95%CI, 0.352 to 1.406). In this subgroup, there were several differences in the baseline characteristics regarding age and gender. The detail of ORR and PFS according to mutations status was shown in the table. The safety profiles in both arms were consistent compared to previous reports. Conclusions: A consistent PFS benefit of afatinib over platinum-doublet chemotherapy was shown regardless the mutation status in patients with uncommon or compound EGFR mutations. The OS data were immature, and further follow-up will be warranted. Clinical trial information: 031180175. [Table: see text] </jats:p>