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01-11-2019 | Non-small-cell lung cancer | News

Further data support lorlatinib as an option in advanced ROS1-positive NSCLC

medwireNews: The early potential of lorlatinib for the treatment of patients with advanced ROS1-positive non-small-cell lung cancer (NSCLC) who are either tyrosine kinase inhibitor (TKI)-naïve or have previously received crizotinib has been re-emphasized in the expanded analysis of a phase I–II trial.

The phase I part of the current study, previously reported by medwireNews, showed that lorlatinib had preliminary antitumor activity in patients with advanced ROS1-positive NSCLC.

The current analysis of the ongoing trial included 69 patients from 28 hospitals in 12 countries worldwide who mainly received lorlatinib 100 mg once daily in continuous 21-day cycles (10 patients from phase I received doses ranging from 10 mg/day to 100 mg twice a day, with five receiving a dose of less than 100 mg/day).

Of these, 30% were TKI-naïve, 58% had previously received crizotinib as their only TKI, and 12% had previously received one non-crizotinib ROS1–TKI or two or more ROS1–TKIs.

During a median 21.1 months of follow-up the objective response rates were 62% in the TKI-naïve patients and 35% in the patients previously treated with crizotinib as their only TKI. The median response durations were 25.3 and 13.8 months, respectively.

There were 11 TKI-naïve patients and 24 crizotinib-treated patients with baseline central nervous system (CNS) metastases, of whom 64% and 50%, respectively, achieved intracranial responses.

“These findings suggest an important role for lorlatinib in effectively treating and controlling CNS metastases in patients with ROS1-positive NSCLC, irrespective of previous crizotinib exposure,” Alice Shaw (Massachusetts General Hospital, Boston, USA) and co-authors write in The Lancet Oncology.

The team also reports median progression free survival durations of 21.0 months in the TKI-naïve patients and 8.5 months in the crizotinib-treated patients, adding that the “median time to intracranial progression could not be estimated at the time of data cutoff.”

No new safety signals were reported in the expansion phase of the study, with the most common grade 3–4 treatment-related adverse events being hypertriglyceridemia (19%) and hypercholesterolemia (14%). Serious treatment-related adverse events occurred in 7% of patients and there were no treatment-related deaths.

Shaw et al conclude: “Because crizotinib-refractory patients have few treatment options, lorlatinib could represent an important next-line targeted agent.”

Michaël Duruisseaux, from Université de Lyon in France, agrees with this statement in an accompanying comment. He says: “This study establishes lorlatinib as an effective treatment option after crizotinib failure in ROS1-positive patients.”

Duruisseaux adds: “A chemotherapy-free crizotinib-lorlatinib sequence is emerging as a treatment strategy of choice, with an expected cumulated progression-free survival of up to 27–28 months.

“Combined with the median overall survival of 51.4 months seen in crizotinib-treated patients in the PROFILE 1001 trial, these data highlight the importance of systematic, reliable ROS1 molecular testing in all patients with non-squamous advanced NSCLC.”

By Laura Cowen

medwireNews is an independent medical news service provided by Springer Healthcare. © 2019 Springer Healthcare part of the Springer Nature group

Lancet Oncol 2019; doi:10.1016/S1470-2045(19)30655-2
Lancet Oncol 2019; doi:10.1016/S1470-2045(19)30716-8