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16-08-2022 | Oncology | News | Article

WCLC 2022

Entrectinib shows potential as first-line treatment for ROS1 fusion-positive advanced NSCLC

Author: Lynda Williams

medwireNews: The latest findings from an integrated analysis of three trials confirm the efficacy of entrectinib for patients with previously treated, locally advanced or metastatic ROS1 fusion-positive non-small-cell lung cancer (NSCLC), and point to a possible role as a first-line agent in this population.

The fourth update from the phase 1/2 STARTRK-1, STARTRK-2, and ALKA-372-001 studies was presented at the IASLC World Conference on Lung Cancer 2022 in Vienna, Austria, by Yun Fan (Zhejiang Cancer Hospital, Hangzhou, China).

Entrectinib had a “manageable safety profile,” Fan told delegates. Treatment-related adverse events (TRAEs) occurred in 95% of the full safety population of 247 patients, most commonly dysgeusia (43%), weight increase (38%), dizziness (35%), constipation (32%), and diarrhea (30%). TRAES led to dose interruption in 36%, reduction in 35%, and discontinuation in 7% of patients, and 43% had TRAEs of grade 3 or more severe.

Moreover, the presenter said that “entrectinib demonstrated robust and durable responses regardless of baseline CNS [central nervous system] status.”

She reported an objective response rate (ORR) of 67.4% for the full efficacy group of 172 patients, 63.3% for the 60 patients with baseline CNS metastases, and 69.6% for the 112 patients without baseline brain disease.

The median duration of response in the three groups was 20.4, 14.6, and 28.6 months, respectively. The corresponding durations of median progression-free survival (PFS) in the overall, baseline CNS metastases, and no baseline CNS metastases groups were a respective 16.8, 11.8, and 25.2 months, while median overall survival (OS) times were 44.1 months, 28.3 months, and unreached.

Exploratory analysis of 67 treatment-naïve patients gave an ORR of 68.7% – including a complete response rate of 14.9% and a partial response rate of 53.7% – and a median duration of response of 35.6 months. In this subgroup, median PFS and OS were 17.7 and 47.7 months, respectively.

Furthermore, when looking only at the intracranial efficacy of entrectinib, the ORR was 49.0% for all 51 patients with confirmed CNS metastases at baseline, increasing to 60.9% among the 23 patients with baseline CNS metastases who were given entrectinib as first-line treatment. The median duration of response was 12.9 months in both these groups and median intracranial PFS was 12.0 and 15.6 months, respectively.

Session discussant Lorenza Landi (‘Regina Elena’ National Cancer Institute, Rome, Italy) said that the exploratory analysis for the efficacy of first-line entrectinib was “very new” because earlier trials in the ROS1 fusion-positive setting of crizotinib, ceritinib, and lorlatinib were all conducted in patients who had previously received chemotherapy.

In addition to “longer follow-up to clearly establish the long-term benefit” of entrectinib, the discussant said it was important to determine the impact of entrectinib in NSCLC harboring both ROS1 and TP53 alterations.

Landi observed that findings from the PFROST study of lorlatinib for ROS1 fusion-positive NSCLC – also reported at the conference – indicate that the agent may be less effective when TP53 mutation is also present (median OS unreached vs 14.6 months), and that a similar relationship was previously reported for crizotinib in the EUCROSS trial.

medwireNews is an independent medical news service provided by Springer Healthcare Ltd. © 2022 Springer Healthcare Ltd, part of the Springer Nature Group

IASLC World Conference on Lung Cancer 2022; Vienna, Austria: 6–9 August

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