Icotinib plus chemotherapy as neoadjuvant treatment for resectable stage II-IIIB EGFR-mutant lung adenocarcinoma: a phase II study (NEOIPOWER).

BACKGROUND

EGFR tyrosine kinase inhibitors (EGFR-TKIs) have shown activity in the neoadjuvant setting of EGFR-mutant (EGFRm) non-small cell lung cancer; however, data on the combination of neoadjuvant EGFR-TKIs plus chemotherapy are limited. This study aimed to evaluate the safety and efficacy of neoadjuvant icotinib plus chemotherapy for stage II-IIIB EGFRm lung adenocarcinoma.

METHODS

NEOIPOWER is a single-arm, phase II study (NCT05104788). Eligible adult patients with resectable, stage II-IIIB, EGFRm lung adenocarcinoma received 8 weeks of 125 mg icotinib three times daily plus two 21-day cycles of chemotherapy (pemetrexed 500 mg/m and carboplatin AUC5 on day 1), followed by surgical resection. The primary endpoint was major pathologic response (MPR) rate. Secondary endpoints were R0 resection rate, objective response rate (ORR), pathologic complete response (pCR), disease control rate (DCR), disease-free survival (DFS), overall survival, and safety.

RESULTS

From October 25, 2021, to April 2, 2023, 30 patients were enrolled and completed neoadjuvant therapy. MPR was observed in 6.7 % of patients (95% CI, 0.8-22.1%), which did not meet the primary endpoint. No patients had pCR. Twenty-eight (93.3 %) patients underwent surgery, of whom 27 (96.4 %) achieved R0 resection, and pathological downstaging was observed in 10 (35.7 %) patients. The ORR was 83.3 % (95% CI, 65.3-94.4 %) and DCR was 96.7 % (95% CI, 82.8-99.9 %) among 30 treated patients. With a median follow-up of 25.0 (range, 6.4-33.6) months, the median DFS was not reached (95% CI, 25.1-not estimable), and the 2-year DFS rate was 92.0 %. Grade 3 treatment-related adverse events (TRAEs) were reported in 6 (20.0 %) patients and mainly included leukopenia (6.7 %) and neutropenia (6.7 %). No grade 4 or 5 TRAEs were observed, and no deaths occurred.

CONCLUSION

Neoadjuvant icotinib combined with chemotherapy did not meet its primary endpoint for MPR rate in resectable stage II-IIIB EGFRm lung adenocarcinoma, but demonstrated a manageable safety profile.