EU Panel Recommends Pralsetinib for RET Fusion+ Advanced NSCLC


The European Medicines Agency’s Committee for Medicinal Products for Human Use has recommended the approval of pralsetinib for use as a single agent in adult patients with RET fusion–positive advanced non–small cell lung cancer who did not receive prior RET inhibition.

Levi Garraway, MD, PhD

Levi Garraway, MD, PhD

The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended the approval of pralsetinib (Gavreto) for use as a single agent in adult patients with RET fusion–positive advanced non–small cell lung cancer (NSCLC) who did not receive prior RET inhibition.1

The recommendation is supported by data from the phase 1/2 ARROW trial (NCT03037385), in which the agent elicited an overall response rate (ORR) of 62% (95% CI, 53%-70%) in 126 patients who previously received platinum-based chemotherapy.2

The median duration of response (DOR) was 22.3 months (95% CI, 15.1–not reached) with pralsetinib in this subset, with a disease control rate (DCR) of 91% (95% CI, 85%-96%) and a clinical benefit rate (CBR) of 74% (95% CI, 65%-81%). Moreover, the median progression-free survival (PFS) with the agent was 16.5 months (95% CI, 10.5-24.1; n = 136).

Among 68 treatment-naïve patients, pralsetinib elicited an ORR of 79% (95% CI, 68%-88%), and the median DOR had not yet been reached (NR; 95% CI, 9.0–NR). In this subset, pralsetinib resulted in a DCR of 93% (95% CI, 84%-98%), a CBR of 82% (95% CI, 71%-91%), and a median PFS of 13.0 months (95% CI, 9.1–NR; n = 75).

Among 25 treatment-naïve patients who were enrolled to trial following revision of eligibility criteria to allow candidates for platinum-based therapy, the agent induced an ORR of 88% (95% CI, 69%-98%). In this subset, the median DOR was NR (95% CI, NR–NR), the DCR was 96% (95% CI, 80%-100%), the CBR was 88% (95% CI, 69%-98%), and the median PFS was NR (95% CI, NR–NR).

“This positive CHMP opinion for [pralsetinib] represents another important step towards our goal of providing effective therapeutics that target genomic drivers of disease for as many cancer patients as possible,” Levi Garraway, MD, PhD, chief medical officer and head of Global Product Development at Roche, stated in a press release. “Advances in personalized medicine also underscore the important of tumor genomic profiling to identify patients who may benefit from targeted therapies.”

ARROW enrolled patients with an advanced or metastatic solid tumor that harbored a RET alteration per local assessment who was at least 18 years of age, had measurable disease per RECIST v1.1 criteria, and had an ECOG performance status of 0 or 1.

In July 2019, criteria were expanded by a protocol amendment that permitted the enrollment of treatment-naïve patients who were candidates for platinum-based therapy and to provide a study population that is more representative of the real-world population.

The phase 1 dose-escalation portion of the research was completed, and the phase 2 dose of pralsetinib was determined to be 400 mg per day. The phase 2 dose-expansion portion of the research is ongoing, and participants are receiving the agent at a daily dose of 400 mg.

The primary end point of the research is ORR per blinded independent central review and RECIST v1.1 criteria, as well as safety. Important secondary end points are DOR, CBR, DCR, PFS, and OS.

Data presented during the 2021 ASCO Annual Meeting showed that at a median follow-up of 17.1 months and data cutoff date of November 6, 2020, 216 patients with RET fusion–positive NSCLC comprised the measurable disease population.

Among those who were treatment-naïve (n = 68), 43 patients were enrolled before the eligibility criteria revision, and 25 were enrolled after. In patients who received prior treatment, 126 received prior platinum therapy and 22 received prior non-platinum treatment.

Among all patients with RET fusion–positive NSCLC, the median age was 60 years (range, 26-87). Forty-eight percent of patients were male, 52% were White, 37% were current or former smokers, 63% had an ECOG performance status of 1, and 38% had brain metastases. Regarding prior therapy received, 58% had platinum-based therapy, 19% had a multikinase inhibitor, and 31% had a PD-(L)1 inhibitor.

Six percent of the 471 patients in the overall study population discontinued pralsetinib because of treatment-related adverse effects (AEs). Treatment-related neutropenia resulted in dose interruption for 15% of patients spanning all tumor types; this toxicity resulted in dose reductions in 14% of all patients. Only 2 patients discontinued pralsetinib because of treatment-related neutropenia.

Other AEs reported in the subgroup of patients with RET fusion–positive NSCLC (n = 233) included neutropenia, aspartate aminotransferase increase, anemia, white blood cell count decreased, alanine aminotransferase increase, hypertension, asthenia, constipation, lymphopenia, diarrhea, blood creatinine increased, dysgeusia, thrombocytopenia, dry mouth, blood creatinine phosphokinase increase, edema, pneumonitis, and hyperphosphatemia.

A final decision regarding the approval of pralsetinib is anticipated from the European Commission in the coming months, according to Roche.


  1. Roche receives positive CHMP opinion for Gavreto (pralsetinib) for the treatment of adults with RET fusion-positive advanced non-small cell lung cancer. News release. Roche. September 17, 2021. Accessed September 17, 2021.
  2. Curigliano G, Gainor JF, Griesinger F, et al. Safety and efficacy of pralsetinib in patients with advanced RET fusion-positive non-small cell lung cancer. J Clin Oncol. 2021;39(suppl 15):9089. doi:10.1200/JCO.2021.39.15_suppl.9089
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