medwireNews: The tyrosine kinase inhibitor (TKI) ceritinib shows potent clinical activity in patients with heavily pretreated, ROS1-positive non-small-cell lung cancer (NSCLC), phase II study data show.
The drug also elicited intracranial responses in patients with brain metastases, Byoung Chul Cho (Yonsei University College of Medicine, Seoul, Republic of Korea) and colleagues report in the Journal of Clinical Oncology.
“Taken together, these data expand the role of ceritinib in patients with ROS1-rearranged NSCLC,” they write.
The study included 32 Korean patients (median age 62 years, 75% women) with ROS1-rearranged advanced NSCLC who received oral ceritinib 750 mg once daily, after a 2-hour fast, in continuous 28-day treatment cycles until disease progression or intolerance.
The patients had a median of three previous treatments before study enrolment, including two who had received crizotinib.
Of the patients enrolled, four (including the two treated with crizotinib) were not evaluable for response by independent radiologic review due to early progression or death (n=3) or withdrawal as a result of adverse events (n=1).
And the lack of clinical benefit in the two crizotinib-treated patients caused the researchers to amend the study protocol to only include crizotinib-naïve patients.
Overall, the objective response rate (ORR) during the median 14-month follow-up period was 62%, with one complete response and 19 partial responses. The ORR of the crizotinib-naïve patients was 67%.
The median duration of response was 21.0 months, the median disease control rate was 81%, and a decrease in tumor burden from baseline was observed in 75% of the 28 evaluable patients.
The researchers also report a median progression-free survival of 9.3 months overall, increasing to 19.3 months for crizotinib-naïve patients. The median overall survival was 24 months.
Among the eight patients with brain metastases at study entry, the intracranial ORR was 25%, with 63% achieving intracranial disease control.
In terms of safety, Cho and team say that the side effects were “manageable and consistent with the established safety profile of ceritinib.”
The most common adverse events were diarrhea (78%), nausea (59%), and anorexia (56%), which mainly occurred at grade 1 or 2.
In an accompanying editorial, Ibiayi Dagogo-Jack and Alice Shaw, both from Massachusetts General Hospital in Boston, USA, say the findings by Cho et al add “another highly effective agent to the growing roster of TKIs for advanced ROS1-positive NSCLC.”
However, they note that “the study also creates a new dilemma in the field, namely which ROS1 TKI should be used for patients with newly diagnosed ROS1-positive lung cancer?”
The editorialists suggest that the antitumor activity of ceritinib “could exceed that of crizotinib in ROS1-positive NSCLC” but caution that toxicity, particularly long-term, chronic daily gastrointestinal adverse effects, may be worse. They also point out that “ceritinib’s activity in ROS1-positive NSCLC is likely confined to crizotinib-naïve patients.”
Dagogo-Jack and Shaw therefore conclude: “Although the performance of ceritinib in this study is promising, a larger global study is needed to establish the drug’s activity, particularly in the [central nervous system].”
“In addition, the safety and efficacy of the alternative ceritinib dosing regimen [450 mg daily with food] warrant further study to maximize the drug’s tolerability.”
By Laura Cowen
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