Use of selpercatinib in a patient with RET-mutated non-small cell lung cancer: case report

Background. The use of the modern targeted drugs in patients with non-small-cell lung cancer (NSCLC) with certain somatic alterations (genetic alterations in EGFR, ALK, ROS1, BRAF, RET genes, etc.) provides a significant increase in overall and disease-free survival with an acceptable toxicity profile. The use of RET inhibitors, such as selpercatinib, has significantly improved prognosis in NSCLC patients with RET gene translocation, since chemotherapy and immunotherapy in this cohort of patients are ineffective options. The RET gene translocation occurs rarely (2–3 % of cases among lung adenocarcinoma), but detection of this genetic alteration with subsequent administration of targeted therapy significantly improves the prognosis of the disease. Case report. We present a clinical case of the efficacy of targeted therapy with selpercatinib in a 60-year-old patient with RET-positive NSCLC. Methods to eliminate toxicity after selpercatinib therapy and therapy response are described. Results. Second-line selpercatinib therapy resulted in partial response in our patient with lung adenocarcinoma and the presence of translocation in RET gene. Adverse effects from targeted therapy were minimized or eliminated by the use of concomitant therapy, temporary cancellation of targeted therapy with subsequent dose reduction and gradual return to full therapeutic doses. Conclusion. This case demonstrates the high significance and importance of genetic testing in patients with lung adenocarcinoma not only for the most common mutations, but also for rarer somatic alterations, such as translocation in the RET gene. Detection of this translocation and subsequent administration of appropriate targeted therapy significantly improves the prognosis of patients.

1. AACR Project GENIE Consortium. AACR Project GENIE: Powering Precision Medicine through an International Consortium. Cancer Discov. 2017; 7(8): 818–31. doi: 10.1158/2159-8290.CD-17-0151.

2. Wang S., Jiang M., Yang Z., Huang X., Li N. The role of distinct co-mutation patterns with TP53 mutation in immunotherapy for NSCLC. Genes Dis. 2020; 9(1): 245–51. doi: 10.1016/j.gendis.2020.04.001.

3. Xiao J., Hu C.P., He B.X., Chen X., Lu X.X., Xie M.X., Li W., He S.Y., You S.J., Chen Q. PTEN expression is a prognostic marker for patients with non-small cell lung cancer: a systematic review and meta-analysis of the literature. Oncotarget. 2016; 7(36): 57832–40. doi: 10.18632/oncotarget.11068.

4. Pécuchet N., Laurent-Puig P., Mansuet-Lupo A., Legras A., Alifano M., Pallier K., Didelot A., Gibault L., Danel C., Just P.A., Riquet M., Le Pimpec-Barthes F., Damotte D., Fabre E., Blons H. Different prognostic impact of STK11 mutations in non-squamous non-small-cell lung cancer. Oncotarget. 2017; 8(14): 23831–40. doi: 10.18632/oncotarget.6379.

5. Rodak O., Peris-Díaz M.D., Olbromski M., Podhorska-Okołów M., Dzięgiel P. Current Landscape of Non-Small Cell Lung Cancer: Epidemiology, Histological Classification, Targeted Therapies, and Immunotherapy. Cancers (Basel). 2021; 13(18): 4705. doi: 10.3390/cancers13184705.

6. Drusbosky L.M., Rodriguez E., Dawar R., Ikpeazu C.V. Therapeutic strategies in RET gene rearranged non-small cell lung cancer. J Hematol Oncol. 2021; 14(1): 50. doi: 10.1186/s13045-021-01063-9.

7. Gainor J.F., Shaw A.T. Novel targets in non-small cell lung cancer: ROS1 and RET fusions. Oncologist. 2013; 18(7): 865–75. doi: 10.1634/theoncologist.2013-0095.

8. Drilon A., Oxnard G.R., Tan D.S.W., Loong H.H.F., Johnson M., Gainor J., McCoach C.E., Gautschi O., Besse B., Cho B.C., Peled N., Weiss J., Kim Y.J., Ohe Y., Nishio M., Park K., Patel J., Seto T., Sakamoto T., Rosen E., Shah M.H., Barlesi F., Cassier P.A., Bazhenova L., De Braud F., GarraldaE., Velcheti V.,SatouchiM.,OhashiK.,PennellN.A.,ReckampK.L., Dy G.K., Wolf J., Solomon B., Falchook G., Ebata K., Nguyen M., Nair B., Zhu E.Y., Yang L., Huang X., Olek E., Rothenberg S.M., Goto K., Subbiah V. Efficacy of Selpercatinib in RET Fusion-Positive Non-Small-Cell Lung Cancer. N Engl J Med. 2020; 383(9): 813–24. doi: 10.1056/NEJMoa2005653.