Retevmo (selpercatinib) Treatment of Lung and Other “RET Fusion” Cancers

Retevmo precision cancer medicine targeting RET in NSCLC patients delays cancer progression better that chemotherapy-immunotherapy.

Charles H. Weaver, MD
4–6 minutes
Home » Lung Cancer » Retevmo (selpercatinib) Treatment of Lung and Other “RET Fusion” Cancers

by Dr. C.H. Weaver M.D. Updated 10/2023

Retevmo (selpercatinib -LOXO-292), a novel precision cancer medicine targeting tumors containing a mutated protein known as RET was approved by the US Food and Drug Administration in May 2020. Retevmo is approved for the treatment of non-small cell lung cancers (NSCLC) and other cancers with RET mutations identified by NGS testing. Retevmo delays cancer progression in patients with RET fusion–positive NSCLC according to data from the phase 3 LIBRETTO-431 trial presented during the October 2023 ESMO Congress and should be considered the first-line standard of care in RET fusion–positive, advanced NSCLC.

About Retevmo (selpercatinib)

Retevmo is an oral precision cancer medicine that is designed to target cancers with genomic alterations in the RET kinase, which include fusions and activating point mutations which lead to overactive RET signaling and uncontrolled cell growth. These “RET fusions” have been identified in approximately 2% of non-small cell lung cancer, 10-20% of papillary and other thyroid cancers, and a subset of other cancers. Activating RET point mutations account for approximately 60% of medullary thyroid cancer. Retevmo was designed to inhibit native RET signaling as well as anticipated acquired resistance mechanisms that could otherwise limit the activity of this therapeutic approach. In the initial clinical trial Retevmo shrank the cancer in 77% of patients with RET fusion cancers originating in the lungs, thyroid and pancreas. 

Non Small Cell Lung Cancer

In an analyses updated in April 2022, among 247 patients with advanced RET fusion-positive NSCLC the confirmed objective response rate was 61% and among 69 treatment-naïve patients, the rate was 84.%. The central nervous system (CNS) response rate was 85%. At a median follow-up of approximately two years the median duration of response is estimated to 20.2 and 28.6 months for previously treated and treatment naïve patients respectively.6

Standard initial treatment for newly diagnosed advanced NSCLC has consisted of platinum plus pemetrexed chemotherapy combined with Keytruda (pembrolizumab) immunotherapy. Overall ~48% of patients respond to this treatment and have an average cancer free survival of 8.8 months.10

The LIBRETTO-431 clinical trial was designed to determine if individuals with a RET fusion mutation could be better treated with Retevmo.7 In the trial 261 individuals with newly diagnosed stage IIIB, IIIC or IV RET mutated NSCLC were treated with either Retevmo at a twice-daily dose or platinum plus pemetrexed chemotherapy with or without Keytruda immunotherapy and directly compared.

Overall, 84% of patients responded to treatment with retevmo compared with 65% treated with standard chemo-immunotherapy. The median duration of response was 24 months with retevmo compared to 11.5 months with chemo-immunotherapy. Patients with measurable CNS disease were also more likely to respond to retevmo.

The most common side effects seen in patients treated with selpercatinib, included hypertension, diarrhea, swelling and minor elevations of liver enzymes.

The study authors concluded that “Retevmo should be considered as a first-line standard of care in RET fusion–positive, advanced NSCLC. The results reinforce the importance of genetic testing to identify RET fusions at the time of diagnosis, to inform initial therapy.”

RET in Thyroid Cancer

Selpercatinib is also currently available for treatment of Thyroid Cancer. RET fusions occur when a portion of the chromosome containing the RET gene breaks and rejoins with another piece of chromosome, creating a fusion protein capable of fueling cancer growth. RET alterations also occur in roughly 10-20% of papillary thyroid cancers (PTC) and the vast majority of medullary thyroid cancers (MTC). Up to half of all RET fusion-positive cancers metastasize to the brain.

Among patients with MTC the response to treatment was 73% in previously untreated patients and 69% in those receiving prior targeted therapies. In patients with previously treated papillary/anaplastic thyroid cancer, the response rate was 79%.

The most common side effects are low white blood count, dry mouth, diarrhea, hypertension, fatigue, edema, decreased platelets, rash, and constipation.

Connect With Others for Support and information

Cancer Connect was the first social network created for people with lung cancer. Founded by oncologists to support cancer patients and their caregivers, over 40 million individuals have accessed Cancer Connect programs since 1997. Cancer Connect is used by leading cancer centers like Dana Farber, Roswell Park and The James at Ohio State to support their patients. Join the conversation, ask questions, share your experience, and learn how the best cancer centers are treating lung cancer from others. Share your experience, ask a question, or start a conversation by posting on Cancer Connect.

References:

  1. abstracts.asco.org/214/AbstView_214_219841.html
  2. Drilon A, Oxnard GR, Wirth L, et al. A phase 1/2 trial of LOXO-292 in patients with RET fusion-positive lung cancers. Presented at: IASLC 2019 World Conference on Lung Cancer hosted by the International Association for the Study of Lung Cancer; September 7-10, 2019; Barcelona, Spain. Abstract PL02.08.
  3. International Association for the Study of Lung Cancer. Registrational data from the LIBRETTO-1 trial demonstrate compelling and durable activity of selpercatinib (LOXO-292) in RET fusion-positive lung cancer. Published September 9, 2019. Accessed September 9, 2019.
  4. FDA approves selpercatinib for lung and thyroid cancers with RET gene mutations or fusions
  5. https://investor.lilly.com/news-releases/news-release-details/lilly-presents-updated-data-retevmor-selpercatinib-advanced-ret
  6. Lilly’s Retevmo (selpercatinib) is the first targeted therapy to demonstrate superior progression-free survival compared to a PD-1 inhibitor plus chemotherapy for adults with newly-diagnosed advanced or metastatic RET fusion-positive non-small cell lung cancer. News release. Eli Lilly and Company. August 4, 2023. Accessed August 4, 2023. https://investor.lilly.com/news-releases/news-release-details/lillys-retevmor-selpercatinib-first-targeted-therapy-demonstrate
  7. Loong HHF, Goto K, Solomon BJ, et al. Randomized phase II study of first-line selpercatinib versus chemotherapy and pembrolizumab in RET fusion-positive NSCLC. Ann Oncol. 2023;34(suppl 2):S1303. doi:10.1016/j.annonc.2023.10.059
  8. FDA approves selpercatinib for locally advanced or metastatic RET fusion-positive non-small cell lung cancer. FDA. September 21, 2022. Accessed October 21, 2023. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-selpercatinib-locally-advanced-or-metastatic-ret-fusion-positive-non-small-cell-lung
  9. Drilon A, Subbiah V, Gautschi O, et al. Selpercatinib in patients with RET fusion-positive non-small-cell lung cancer: updated safety and efficacy from the registrational LIBRETTO-001 phase I/II trial. J Clin Oncol. 2023;41(2):385-394. doi:10.1200/JCO.22.00393
  10. Gandhi L, Rodríguez-Abreu D, Gadgeel S, et al. N Engl J Med. 2018;378(22):2078-2092. doi:10.1056/NEJMoa1801005
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