385P - Efficacy and safety of pyrotinib in untreated, advanced non-small cell lung cancer with HER2 mutations: A parallel, multi-center, multi-cohort patient-centric study (CTONG1702 and 1705)

Background

Large-scale screening was needed to identify rare genetic mutations. However, overly restrictive inclusion and exclusion criteria limit patients for trial participation. Here, we reported a patient-centric study with parallel, multi-center, multi-cohort for the enrollment of untreated, advanced non-small cell lung cancer (NSCLC) with HER2 mutations.

Methods

This study constituted of an open-label, phase II adaptive umbrella trial (CTONG 1702) and a real-world study (RWS) (CTONG 1705), which were simultaneously initiated. Untreated advanced NSCLC patients were screened by NGS. HER2 mutant patients eligible for pyrotinib were enrolled in criteria fulfilled (CF) cohort; patients ineligible but willing to receive pyrotinib by compassionate use (CU) enrolled in CU cohort; patients receiving standard treatment in clinical practice enrolled in RWS cohort. The primary endpoint of two pyrotinib cohorts was objective response rate (ORR).

Results

932 patients were screened and 48 HER2 mutant patients were included in analysis (CF cohort: n=28; CU cohort: n=12; RWS cohort: n=8). At the time of data cutoff (December 1, 2021), the median follow-up time was 16.5 months (range: 0.8 to 33.8). Pyrotinib achieved an ORR of 35.7% and 16.7%, and disease contral rate of 89.3% and 83.4% in CF and CU cohorts, respectively. Median progression free survival was 7.3, 4.7, 3.0 months and median overall survival was 14.3, 14.1, 12.2 months in CF, CU and RWS cohorts, respectively. No significant difference on efficacy of pyrotinib was observed in HER2 mutation subtypes, and in patients with or without brain metastasis. The most frequent treatment-related adverse events (TRAEs) of pyrotinib were diarrhea (87.5%), rash (35.0%), and AST increased (17.5%). Frequency of grade 3/4 TRAEs was 10.7% and 33.3% in CF and CU cohorts. Table: 385P

Efficacy of pyrotinib and standard anti-tumor therapy in this patient-centric study

Conclusions

Pyrotinib exhibited promising efficacy and acceptable safety in untreated NSCLC patients with HER2 mutations. Benefits were also observed from the compassionate use of pyrotinib.

Clinical trial identification

NCT03574402 (CTONG1702), NCT03605602 (CTONG1705).

Editorial acknowledgement

Legal entity responsible for the study

Chinese Thoracic Oncology Group (CTONG).

Funding

Jiangsu Hengrui Pharmaceuticals Co., Ltd.

Disclosure

Q. Zhou: Financial Interests, Personal, Other, honoraria: AstraZeneca, Boehringer Ingelheim, BMS, Eli Lilly, MSD, Pfizer, Roche, Sanofi. Y. Wu: Financial Interests, Personal, Advisory Role: Roche, AstraZeneca, Eli Lilly, Boehringer Ingelheim, Sanofi, MSD, BMS. All other authors have declared no conflicts of interest.