ESMO: Lilly's Retevmo drives major benefits in lung, thyroid cancers as Roche bows out of competition

Eli Lilly is on a roll with its RET inhibitor Retevmo, with new trial results showing the drug can offer dramatic benefits in the treatment of certain lung and thyroid cancers. 

Detailed phase 3 data released at the European Society for Medical Oncology 2023 congress showed that Retevmo beat the combination of Merck’s Keytruda and chemotherapy in RET fusion-positive non-small cell lung cancer. In a separate trial, the Lilly drug also outperformed Exelixis’ Cabometyx or Sanofi’s Caprelsa in RET-mutant medullary thyroid cancer.

First up, the LIBRETTO-431 study showed that Retevmo reduced the risk of progression or death by 53.5% compared with the Keytruda-chemo combination in patients with newly diagnosed RET fusion-positive NSCLC, investigators said.

The Lilly drug more than doubled the median progression-free survival time to 24.8 months. That figure compared with 11.2 months for the Keytruda-chemo takers.

The trial is the first randomized study to show superior progression-free survival from a targeted therapy versus a combination of a checkpoint inhibitor and chemotherapy in a biomarker-selected patient population.

Retevmo’s progression-free survival improvement came in at 51.8% if counting the entire trial population, which also included a small group of patients who didn’t receive Keytruda.

Data on whether Retevmo prolonged patients’ lives remains immature. On a positive note for the therapy, with a 4% lower risk of death, Retevmo didn’t appear to show a potential detriment to overall survival. About 75% of patients in the control arm later went on to receive a RET inhibitor.

Investigators recorded seven deaths related to side effects in the Retevmo arm, including two cases deemed related to treatment. No deaths stemmed from side effects in the control group. The rate of serious side effects of grade 3 or above was generally higher for Retevmo, although the trial investigators noted that the majority of treatment-emergent adverse events were brought under control by dose modifications.

All told, Retevmo should be considered a first-line standard of care in RET fusion-positive advanced NSCLC, trial investigator Herbert Loong from the Chinese University of Hong Kong said in a presentation.

In the second study, coded LIBRETTO-531, Retevmo cut the risk of progression or death by 72% versus Cabometyx or Caprelsa in patients with RET-mutant medullary thyroid cancer (MTC) who had not previously received a kinase inhibitor. The analysis was performed by a blinded, independent data review committee.

MTC is a rare neuroendocrine tumor originating from the thyroid, accounting for less than 5% all thyroid cancer cases.

By the time of the analysis, about 90% of patients in the study were still alive. Retevmo was linked to a 62.6% reduction in the risk of death, which doesn’t come with any statistical rigor.

The Lilly drug also showed a favorable tolerability profile. While 76.3% of patients in the control arm experienced grade 3 or above treatment-emergent side effects, the rate was 52.8% in the Retevmo group.

Retevmo’s MTC win comes as Roche is in the process of pulling an accelerated approval in MTC for its rival RET inhibitor Gavreto. Roche said its phase 3 confirmatory trial was no longer feasible.

In fact, Roche has decided to return Gavreto back to its original developer Blueprint Medicines after seeing little sales potential.

Meanwhile, Gavreto’s phase 3 AcceleRET-Lung trial remains ongoing in a design similar to Retevmo’s LIBRETTO-431 for the first-line treatment of NSCLC.