medwireNews: The oral tyrosine kinase inhibitor pyrotinib is well tolerated and shows promising antitumor activity in people with HER2-mutated non-small-cell lung cancer (NSCLC), phase 2 study data show.
Caicun Zhou (Tongji University School of Medicine, Shanghai, China) and team explain that between 1% and 4% of NSCLCs carry a mutation in HER2 but to date there is no approved treatment for patients with this type of disease.
They say: “Despite the fast development of targeted therapies against other oncogenic drivers, treatment targeting HER2 mutations in NSCLC is poorly described.”
To address this, the researchers examined the efficacy and safety of pyrotinib in 60 patients (55% women, median age 57 years) with stage IIIB (3.3%) or IV (96.7%) HER2-mutant NSCLC.
Pyrotinib was previously approved in China for the treatment of HER2-positive advanced breast cancer in combination with capecitabine, the team notes.
All patients received pyrotinib 400 mg/day for 21-day cycles until disease progression, unacceptable toxicity, withdrawal of consent, or investigator decision. None had received prior immunotherapy, but the entire cohort had previously been treated with at least one line of platinum-based chemotherapy.
During a median 11.7 months of follow-up, the independent review committee-assessed objective response rate (ORR) was 30.0%, all of which were partial responses. The median response duration was 6.9 months.
Writing in the Journal of Clinical Oncology, Zhou and co-authors note that this ORR compares favorably with other treatments. “According to the previous reports, objective response rate with standard second-line chemotherapy is no greater than 10%,” they write.
A further 55.0% of patients had stable disease and 21.7% had stable disease for at least 21 weeks.
The team also reports that median progression-free survival (PFS) was 6.9 months and median overall survival (OS) was 14.4 months, with 12-month PFS and OS rates of 22.5% and 69.1%, respectively.
Nearly all (98.3%) patients reported at least one treatment-related adverse event (TRAE) during the median 10 cycles of treatment; 26.7% of these were grade 3 and 1.7% were grade 4 (one patient with elevated gamma-glutamyltransferase).
One patient discontinued treatment due to an AE and there were no treatment-related deaths.
Noting that diarrhea was the most common TRAE, occurring at grade 3 in 20% of patients, Zhou et al suggest: “To avoid diarrhea, the most common adverse event attributable to pyrotinib, prophylactic loperamide is recommended to patients.”
The researchers conclude: “Pyrotinib (400 mg daily) could be given to patients with HER2-mutant advanced NSCLC who had received at least 1 prior platinum-based chemotherapy.”
The drug will now be tested in a global, multicenter, randomized phase 3 trial.
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