Crizotinib offered a 71.7% objective response rate (ORR) and a median duration of response (DOR) of 19.7 months in East-Asian non-small cell lung cancer (NSCLC) patients harbouring c-ros oncogene 1 (ROS1) rearrangements. This was concluded by investigators from China, Japan, South-Korea, and Taiwan who published the results of the trial in the Journal of Clinical Oncology (JCO) on March 29, 2018.

“Approximately 1% to 2% of NSCLCs harbour a ROS1 rearrangement”, first author Prof. Wu Yi-Long, Guangdong General Hospital and Guangdong Academy of Medical Sciences in Guangzhou, People’s Republic of China, and colleagues wrote in JCO.

The Phase II open-label study enrolled 127 East-Asian patients with confirmed ROS1-positive NSCLC who had received up to three prior lines of systemic therapy. Participants received two oral doses of 250 mg crizotinib daily until progression disease (RECIST 1.1) as confirmed by an independent radiological review (IRR). The primary efficacy endpoint was ORR by IRR.

Crizotinib (XalkoriⓇ, Pfizer Inc.) is an inhibitor of anaplastic lymphoma kinase (ALK), ROS1, and the hepatocyte growth factor receptor (MET).

Figure 1. Responses observed with crizotinib in East-Asian patients with ROS1-rearranged NSCLC.

At the time of the data cut-off, 49.6% of patients were still receiving crizotinib-treatment. Seventeen complete responses and 74 partial responses (Figure 1) were observed, translating into an ORR of 71.7% (95% CI, 63.0% – 79.3%) by IRR. Responses were lasting, the median DOR was 19.7 months (95% CI, 14.1 months – not reached), and irrespective of the number of prior lines of therapy The median progression-free survival (PFS) by IRR was 15.9 months (95% CI, 12.9 – 24.0).

The authors reported no new toxicities. The most common adverse reactions which occur in ≥25% of patients treated with crizotinib are vision disorders, nausea, diarrhoea, vomiting, oedema, constipation, elevated transaminases, fatigue, decreased appetite, upper respiratory tract infection, dizziness, and neuropathy.

References

1. Wu YL et al. J Clin Oncol 2018;JCO2017755587 DOI: 10.1200/JCO.2017.75.5587
2. Pfizer Inc. XalkoriⓇ (crizotinib) USPI, revised 2/2018