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26-08-2022 | Non-small-cell lung cancer | News

ARROW update demonstrates first-line pralsetinib benefit for advanced RET fusion-positive NSCLC

Author: Lynda Williams

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medwireNews: Updated findings from the ARROW trial show that pralsetinib has “robust efficacy” for the first-line treatment of locally advanced or metastatic, RET fusion-positive, non-small-cell lung cancer (NSCLC), the investigators say.

The latest analysis, published in the Annals of Oncology, includes data for 281 patients who were given the recommended phase 2 pralsetinib dose of 400 mg/day in the first or second line, say Julien Mazieres (Hôpital Larrey, Toulouse, France) and co-authors.

After a median follow-up of 17.1 months, 110 of the 233 patients in the intention-to-treat population who began pralsetinib by May 2020 were continuing on treatment; discontinuations included 74 because of disease progression and 34 because of adverse events (AEs).

The intention-to-treat group included 75 treatment-naïve patients, 136 patients who had previously received platinum-based chemotherapy, and 22 patients who had received another type of chemotherapy.

All of the assessed treatment-naïve patients achieved tumor shrinkage; the objective response rate (ORR) was 72% and the disease control rate was 91%, with the mediation duration of response unreached after a median 7.4 months of follow-up.

And after a median 9.2 months’, progression-free survival (PFS) was 13.0 months with estimated 6- and 12-month rates of 80% and 53%, respectively. The corresponding values for overall survival (OS) after a median 12.8 months of follow-up were unreached, 92%, and 82%.

For patients given pralsetinib after platinum-based chemotherapy, 97% of the 120 assessed individuals achieved tumor shrinkage and the ORR was 59%. After a median follow-up of 16.7 months, the median duration of response was 22.3 months. After a median 18.4 months’, the median PFS was 16.5 months, and after a median follow-up of 20.1 months, median OS was not reached, with OS rates at 6 and 12 months of 85% and 72%, respectively.

All 10 patients with measurable intracranial metastases at baseline experienced shrinkage and seven achieved an intracranial response to pralsetinib, all of whom were given the RET inhibitor in the second line. Median duration of intracranial response was 10.5 months, with 71% and 36% of patients continuing to respond after 6 and 12 months, respectively.

Overall, the median duration of treatment in the study was 7.9 months and the median dose intensity was 92%, with 7% of 281 patients discontinuing treatment due to pralsetinib-related AEs. There were “no new safety signals,” the team says.

The authors describe the incidence of grade 3–4 treatment-related events as being “comparable to patients receiving chemotherapy with or without an immune checkpoint inhibitor.”

Focusing on the grade 3–4 treatment-related AEs in the treatment-naïve arm, the most common events were neutropenia (18%), hypertension (10%), elevated blood creatine phosphokinase (9%), and lymphopenia (9%).

The most common serious treatment-related AEs in both the treatment-naïve and previously treated patient groups were pneumonitis (5% both) and pneumonia (6 and 4%, respectively), and pneumonitis was the most common event leading to discontinuation (3 and 2%).

“The updated analysis of the ARROW study presented here supports the approval of pralsetinib as the first and only RET inhibitor for the first-line treatment of patients [with] RET fusion-positive NSCLC in the European Union,” in addition to its approvals for use in the second line in the USA and other countries, the researchers write.

Mazieres et al conclude: “These results show the importance of early comprehensive biomarker testing that includes fusions for all patients with metastatic NSCLC prior to treatment initiation to inform optimal healthcare decisions.

“Results from the phase III AcceleRET Lung study may further support the use of pralsetinib for RET fusion–positive NSCLC in the first-line setting.”

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

Ann Oncol 2022; doi:10.1016/j.annonc.2022.08.002

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