NEW YORK – A Phase II trial conducted in China has demonstrated that Jiangsu Hengrui Medicine's pyrotinib elicited promising antitumor activity and was safe and tolerable in patients with HER2-mutated, advanced non-small cell lung cancer after platinum-based chemotherapy.
Pyrotinib, which in 2018 was granted approval in China for the treatment of advanced HER2-positive breast cancer in combination with chemotherapy, is a pan-HER2 tyrosine kinase inhibitor. The agent is currently being evaluated in early-phase clinical trials for multiple HER2-mutated or HER2-expressing solid tumors, including breast cancer, gastric cancer, and NSCLC.
The Phase II study in NSCLC, the results for which were recently published in the Journal of Clinical Oncology, enrolled 60 patients with stage IIIB or IV, HER2-positive NSCLC who had previously received at least one line of platinum chemo. The patients received 400 mg of oral pyrotinib per day until disease progression, unacceptable toxicity, withdrawal of consent, or investigators decided to discontinue patients on treatment.
After a median follow-up of 11.7 months, the overall response rate was 30 percent and the median duration of response was 6.9 months. At 12 months, the overall survival rate was 69 percent, though the study authors acknowledged that as a Phase II trial with a limited sample size and no control arm, the overall survival figures do not reflect the agent's clinical benefit. As such, the investigators cited the need for data from a randomized Phase III trial, which they said is currently in the planning stages.
Of note, the study was also designed to assess pyrotinib's antitumor activity within specific subgroups of patients, stratified by the type of HER2 mutation their tumors harbored. The groups included 44 patients with a 12 base pair exon 20 insertion, six patients with G776 mutations, five patients with a nine base pair exon 20 insertion, four patients with L755P mutations, and one patient with a V777L mutation. Pyrotinib elicited responses in all of these subgroups, and the overall response rate was similar for patients who did and did not have brain metastases.
In terms of safety and tolerability, the investigators noted that adverse events — the most common of which was diarrhea — were similar to what they had seen in pyrotinib breast cancer trials.
HER2-positive NSCLC accounts for one to four percent of lung cancer diagnoses, wrote Caicun Zhou of Shanghai Pulmonary Hospital, who authored the Journal of Clinical Oncology study along with colleagues. And while HER2 expression in breast cancer is associated with improved survival with HER2-targeting drugs such as trastuzumab (Genentech's Herceptin) and pertuzumab (Genentech's Perjeta), such an association is not clear in lung cancer. As such, drug developers and experts have focused on HER2 mutation status, instead of HER expression, as a better way to identify lung cancer patients who might respond to anti-HER2 drugs.
The US Food and Drug Administration in May granted AstraZeneca and Daiichi Sankyo's fam-trastuzumab deruxtecan-nxki (Enhertu), a potential competitor to pyrotinib, breakthrough therapy designation as a treatment for HER2-mutated, metastatic non-small cell lung cancer that has progressed after platinum-based therapy.