P86.02 Pyrotinib Combined with Apatinib for HER2-Mutant Non-Small Cell Lung Cancer: Interim Analysis from a Phase II Clinical Study

Abstract

Currently, there has been no approved tyrosine kinase inhibitors (TKIs) for non-small cell lung cancer (NSCLC) harboring HER2 mutations, resulting in an unmet need of this molecular entity. We performed this phase II study to assess the efficacy and safety of pyrotinib combined with apatinib in HER2-mutant advanced NSCLC patients who had failed to prior treatment. Patients with metastatic HER2-mutant lung adenocarcinomas who had been pretreated with chemotherapy or other TKIs were enrolled to administer pyrotinib (dose of 400mg once daily) in combination with apatinib (dose of 250mg once daily) for 28-day cycles. The primary endpoint was objective response rate (ORR), and the second endpoint included progression-free survival (PFS), duration of response (DoR), disease control rate (DCR), overall survival (OS) and safety. The trial was approved by ethics committee and registered to Chinese Clinical Trial Registry (ChiCTR1900021684). All participants of this study provided written informed consent. Between March 5, 2019, and January 20, 2020, 14 patients were enrolled and received pyrotinib with apatinib combination therapy, and all of them were stage IV at baseline. Seven (50.0%) patients had received first-line platinum-based chemotherapy or afatinib treatment, and the others had received at least 2 lines of prior therapy (range, 2-6). At the last follow-up time July 14, 2020, among these 14 evaluable patients, the ORR was 35.7% (5/14), and it showed no difference between patients with or without brain metastases (ORR, 40.0% vs 33.3%; median PFS, 6.6 vs. 8.0 months, P = 0.623). All subgroups of patients (10 with exon 20 insertions, 2 with missense mutations and 2 with amplifications) showed disease control with a DCR of 100%. The median PFS, DoR and OS were 8.0 (95%CI: 5.8-10.2), 5.3 (95%CI: 3.6-7.0) and 12.9 (95%CI: 3.8-22.0) months, respectively. The ORR in patients who administered pyrotinib with apatinib as second-line and third- or above-line treatment was 28.6% (2/7) and 42.9% (3/7), respectively; and median PFS did not differ in these two subgroups [8.8 (95%CI: 6.6-11.0) vs. 6.1 (95%CI: 4.0-8.2) months; HR=0.362; P = 0.144]. Common treatment-related adverse events included diarrhea (7.1%, grade 3; 64.3%, grade 2), hypertension (21.4%, grade 2; 50.0%, grade 1) and anorexia (57.1%, grade 1). No treatment-related deaths were reported. Patient characteristics at baseline and response for pyrotinib with apatinibTabled 1ParametersGroupsN (%)Age>602 (14.3)≤6012 (85.7)GenderMale7 (50.0)Female7 (50.0)Molecular variantA775_G776insYVMA9 (64.3)P780_Y781insGSP1 (7.1)G776V1 (7.1)R811L with Q820K1 (7.1)HER2 amplification2 (14.4)Prior lines of treatment17 (50.0)23 (21.4)≥34 (28.6)Brain metastasesPresence5 (35.7)Absence9 (64.3)Partial responseG766V HER2 amplification A775_G776insYVMA1 (7.1) 1 (7.1) 3 (21.4) Open table in a new tab Pyrotinib in combination with apatinib showed favorable antitumor activity and acceptable safety in heavily pretreated NSCLC patients with diverse HER2 mutations.