Phase II clinical trial of everolimus in a pan-cancer cohort of patients with mTOR pathway alterations Journal Article
| Authors: | Adib, E.; Klonowska, K.; Giannikou, K.; Do, K. T.; Pruitt-Thompson, S.; Bhushan, K.; Milstein, M. I.; Hedglin, J.; Kargus, K. E.; Sholl, L. M.; Tsuji, J.; Hyman, D. M.; Sisk, A.; Shapiro, G. I.; Vargas, H. A.; Harding, J. J.; Voss, M. H.; Iyer, G.; Kwiatkowski, D. J. |
| Article Title: | Phase II clinical trial of everolimus in a pan-cancer cohort of patients with mTOR pathway alterations |
| Abstract: | Purpose: This was a multicenter, histology-agnostic, single-arm prospective phase II trial of therapeutic activity of everolimus, an oral mTORC1 inhibitor, in patients with advanced solid tumors that harbored TSC1/TSC2 or MTOR mutations. Patients and Methods: Patients with tumors with inactivating TSC1/TSC2 or activating MTOR mutations identified in any Clinical Laboratory Improvement Amendments (CLIA)-certified laboratory were eligible. Patients were treated with everolimus 10 mg once daily until disease progression or unacceptable toxicity. The primary endpoint was objective response rate (ORR). Whole-exome sequencing was performed to identify co-occurring genomic alterations. Results: Between November 2015 and October 2018, 30 patients were enrolled at Dana-Farber Cancer Institute and Memorial Sloan Kettering Cancer Center. Tumors harbored TSC1 (13/30), TSC2 (15/30), concurrent TSC1 and TSC2 (1/30), or MTOR (1/30) mutations. The most common treatment-related adverse event of any grade was mucositis (8/30, 27%); 1 patient had fatal pneumonitis. Partial responses were seen in 2 patients [7%; 95% confidence interval (CI), 1%–22%]. Median progression-free survival was 2.3 months (95% CI, 1.8–3.7 months) and median overall survival (OS) was 7.3 months (95% CI, 4.5–12.7 months). There was no clear association between other genomic alterations and response. Of the 2 patients with objective response, 1 had upper tract urothelial carcinoma with biallelic inactivation of TSC1 and high tumor mutation burden, and the other had uterine carcinoma with biallelic TSC2-inactivating mutations and PEComa-like pathologic features. Conclusions: Everolimus therapy had a disappointing ORR (7%) in this pan-cancer, mutation-selected, basket study. © 2021 American Association for Cancer Research. |
| Journal Title: | Clinical Cancer Research |
| Volume: | 27 |
| Issue: | 14 |
| ISSN: | 1078-0432 |
| Publisher: | American Association for Cancer Research |
| Date Published: | 2021-07-15 |
| Start Page: | 3845 |
| End Page: | 3853 |
| Language: | English |
| DOI: | 10.1158/1078-0432.Ccr-20-4548 |
| PROVIDER: | scopus |
| PMCID: | PMC8282751 |
| PUBMED: | 33727259 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 2 August 2021 -- Source: Scopus |
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