1246P - PIT-3: A multicenter phase II trial of erlotinib induction followed by surgery in stage IIIA (N2) EGFR mutated non-small cell lung cancer

Background

A multicenter phase II study, PIT-3 (Personized Induction Therapy-3), was performed to investigate the efficacy and safety of erlotinib induction followed by surgery in patients with stage IIIA (N2) EGFR mutated non-small cell cancer (NSCLC).

Methods

Patients with stage IIIA (pathologically confirmed N2) NSCLC with activating EGFR mutations (exon 19 deletion or exon 21 L858R mutation) were enrolled in this study. Patients received 150 mg of erlotinib once daily for 8 weeks, followed by surgery. The primary endpoint was the 2-year progression-free survival (PFS) rate. Key secondary endpoints included overall survival (OS), objective response rate (ORR), pathological response, feasibility, and toxicity.

Results

Of the 25 patients enrolled between April 2017 and February 2021, 24 received induction therapy and 23 underwent lobectomy (n = 19) or bilobectomy (n = 4) with mediastinal lymph node dissection. The ORR was 67% (16/24), and the complete resection rate was 83% (19/23). None of the patients achieved a pathological complete response. The respective 2-year PFS and OS rates were 16.7% (90% CI: 6.6-30.8%) and 91.7% (95% CI: 70.6-97.9%) (median follow-up time: 40.3 months). The primary end point was not met. EGFR-TKIs were administered to all of 20 patients who experienced a relapse. Although the 2-year PFS and OS rates in 11 patients with tumors harboring exon 19 deletions (27.3% and 100%, respectively) were higher than those in 13 patients with exon 21 L858R (7.7% and 84.6%, respectively), no statistically significant differences (P = 0.35 and P = 0.12, respectively) were observed. Grade (G) 3 adverse events (AEs) during erlotinib induction occurred in 3 patients (13%). No G4/5 or unexpected AEs occurred. No intraoperative complications were observed. G3/4 postoperative complications occurred in eight (35%) patients. No serious wound healing complications occurred. No 90-day postoperative mortality was observed.

Conclusions

Erlotinib induction followed by surgery can be safely performed in patients with stage IIIA (N2) EGFR mutated NSCLC. However, this strategy is insufficient to control postoperative relapse. EGFR-TKIs administration after relapse may substantially prolong OS.

Clinical trial identification

UMIN: 000026197, jRCT: s031180404.

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.