The kinase inhibitor is a promising treatment option for patients with MET exon 14 skipping mutation non–small cell lung cancer.
New data demonstrate capmatinib (Tabrecta; Novartis) as a promising treatment option for patients with MET exon 14 skipping mutation (METex14) non–small cell lung cancer (NSCLC).1
A kinase inhibitor, capmatinib is approved by the FDA for the treatment of adult patients with metastatic NSCLC whose tumors have a mutation that leads to MET exon 14 skipping. This approval was based on the phase 2 GEOMETRY (NCT02414139) mono-1 study. Results of the study were presented at the virtual 2021 American Society of Clinical Oncology Annual Conference.2
The findings include data from the GEOMETRY study's new cohort 7 and updates some previously reported analyses.1 According to investigators, capmatinib achieved overall response rate (ORR) of 65.6% (95% CI, 46.8-81.4) in the first-line setting for cohort 7, and 67.9% ORR (95% CI, 47.6-84.1) in cohort 5b. In the second-line setting, 51.6% ORR was achieved in the new expansion cohort.1,3
Capmatinib also demonstrated a median duration of response (DOR) of 12.6 months (95% CI, 5.6-not estimable [NE]) among treatment-naive patients in cohort 5b. DOR for treatment-naive patients in cohort 7 is NE. Among previously treated patients, DORs of 9.7 months (95% CI, 5.61-3.0) and 8.4 months (95% CI, 4.2NE) were found in cohort 4 and cohort 6, respectively.3
Additionally, the study found a mature median overall survival (OS) rate of 20.8 months (95% CI, 12.42-not estimable [NE]) for treatment-naive patients in cohort 5b, and 13.6 months (95% CI, 8.61-22.24) in previously treated patients in cohort 4. Median OS for cohorts 6 and 7 are not yet reached, according to the authors.1,3
Overall, 160 patients with METex14 who received capmatinib 400 mg twice daily were analyzed. Although data for cohort 7 are still immature, the authors announced that median progression-free survival was 10.8 months (95% CI, 6.87-NE).
"This new analysis further supports [capmatinib] as a cornerstone targeted treatment for [patients with] METex14 NSCLC and highlights the importance of biomarker testing," Juergen Wolf, MD, from the Center for Integrated Oncology, University Hospital of Cologne, Germany, and lead investigator of the GEOMETRY study, said in a press release.3 "The impressive overall survival outcome and confirmed outstanding response in the first-line setting will help oncologists decide upon a therapeutic option for patients."
According to investigators, the safety profile remained unchanged across all GEOMETRY study cohorts (N=373), with 98.4% of patients reporting at least 1 adverse event (AE) (68.6% grade 3/4) regardless of causality, and 50.9% of patients reporting at least 1 serious AE. In 16.1% of patients, AEs leading to discontinuation (10.5% grade 3/4) were reported.1,3
Serious AEs reported in patients taking capmatinib include lung or breathing problems, liver problems, and risk of photosensitivity. The most commonly reported AEs (≥ 20% all grades) include swelling of the hands or feet, nausea, tiredness, weakness, vomiting, loss of appetite, and changes in certain blood tests.2
1. Wolf J, Garon EB, Groen HJM, et al. Capmatinib in MET exon 14-mutated, advanced NSCLC: updated results from the GEOMETRY mono-1 study. J Clin Oncol 2021;39(suppl 15; abstr 9020). doi:10.1200/JCO.2021.39.15_suppl.9020
2. Tabrecta (capmatinib) tablets. Prescribing information. Novartis; 2020. Accessed June 8, 2021. https://www.novartis.us/sites/www.novartis.us/files/tabrecta.pdf
3. Novartis announces Tabrecta first published overall survival and updated overall response data in patients with METex14 metastatic NSCLC. News release. Novartis. June 4, 2021. Accessed June 9, 2021. https://www.novartis.com/news/media-releases/novartis-announces-tabrecta-first-published-overall-survival-and-updated-overall-response-data-patients-metex14-metastatic-nsclc