Pyrotinib Shows ‘Promising’ Activity For HER2-Positive Advanced NSCLC

Author: By Lynda Williams, Senior medwireNews Reporter

medwireNews: Early study findings suggest that patients with HER2 mutation-positive advanced non-small-cell lung cancer (NSCLC) may benefit from treatment with the targeted agent pyrotinib.

Following the approval of the oral irreversible tyrosine kinase inhibitor in China for HER2-positive advanced breast cancer, the investigators hypothesised that the agent could offer a novel treatment for lung adenocarcinomas, up to 4% of which harbour HER2 mutations.

The phase II open-label study included 60 patients who had received at least one line of platinum-based chemotherapy for stage IIIB (3.3%) or IV (96.7%) disease, and 41.7% had received at least two lines of treatment previously.

As reported in the Journal of Clinical Oncology, pyrotinib 400 mg/day given in 21-day cycles achieved an independent review committee-assessed objective response in 30.0% of patients, all of which were partial.

More than half (55.0%) of the patients had stable disease, with 21.7% doing so for at least 24 weeks. The median duration of response was 6.9 months, and this was ongoing in 33.3% of responders at time of data analysis, say Caicun Zhou, from Tongji University School of Medicine in Shanghai, China, and co-authors.

Median progression-free survival was 6.9 months and the median overall survival was 14.4 months, with 12-month rates for these endpoints of 22.5% and 69.1%, respectively.

Further analysis of patients by mutation types gave an objective response rate of 27.3% for the 44 patients with a 12-bp exon 20 insertion, including one patient with an EGFR single nucleotide polymorphism.

In addition, responses were reported for 16.7% of the six patients with G776 mutations, 60.0% of the five patients with a 9-bp exon 20 insertion, and 25.0% of the four patients with an L755P mutation, as well as for the one patient with a V777L mutation.

However, the researchers emphasize that the small study size meant they were “unable to adequately compare the clinical benefit of different subtypes in HER2 mutations.”

After a median of 10 treatment cycles, 98.3% of patients had sustained at least one treatment-related adverse event (TRAE), most commonly diarrhoea (91.7%), elevated creatinine (30.0%), vomiting (28.3%) and elevated alanine aminotransferase or aspartate aminotransferase (each 15.0%).

Diarrhoea was again the most common grade 3 TRAE, affecting 20.0%; there was one grade 4 event of elevated gamma-glutamyltransferase, but no grade 5 events.

Further investigation revealed that 83.3% of patients experienced diarrhoea in their first treatment cycle after a median 4.5 days and this lasted a median 6.0 days. Grade 3 diarrhoea occurred in 11.7% of patients during the first cycle, and was significantly more common in patients aged at least 65 years than younger individuals (50.0 vs 12.5%).

While noting that “the incidence of diarrhea gradually declined” in subsequent cycles of pyrotinib, Caicun Zhou and co-workers say that in the future “prophylactic loperamide will be recommended to patients.”

They conclude that “pyrotinib as a single agent showed promising antitumor activity and an acceptable safety profile in chemotherapy-treated patients with HER2-mutant NSCLC” and that a “global, multicenter, randomized phase III trial is being planned and will be started soon.”

Reference

Zhou C, Li X, Wang Q, et al. Pyrotinib in HER2-mutant advanced lung adenocarcinoma after platinum-based chemotherapy: a multicenter, open-label, single-arm, phase II study. J Clin Oncol; Advance online publication 2 July 2020. DOI: 10.1200/JCO.20.00297