In non-indicated advanced solid tumors with relevant alterations, alectinib (Alecensa®; Genentech/Roche), a Food and Drug (FDA-) approved drug for ALK-positive, metastatic non-small cell lung cancer (NSCLC), showed activity in patients with ALK–rearranged advanced solid tumors other than NSCLC.
In NSCLC, cancers with ALK mutations or amplification were not responsive to ALK inhibition. This is one of the outcomes of the MyPathway trial (NCT02091141), a multi-basket study assessing approved therapies, including alectinib.
The study results also demonstrated that adverse events were consistent with the known alectinib safety profile.
The findings of the study were presented by Funda Meric-Bernstam, MD, Chair of the Department of Investigational Cancer Therapeutics at the University of Texas MD Anderson Cancer Center in Houston, Texas, at the annual meeting of the American Association for Clinical Research (AACR), held April 8-13, 2022, in New Orleans, LA (Abstract nr CT032).
The study team analyzed alectinib activity and safety in a pan-tumor population with ALK alterations included in MyPathway study. Enrolled patients were at least 18 years old and had metastatic tumors with ALK gene rearrangements, putative activating non-synonymous ALK mutations, and/or ALK gene amplification. All patients received alectinib.
The primary endpoint was an investigator-assessed objective response rate (ORR) which comprised a complete response (CR) plus a partial response (PR). Other endpoints included duration of response (DoR), disease control rate (DCR) defined as a CR plus PR plus stable disease (SD) longer than 4 months, progression-free survival (PFS), and safety.
Until 18 November 2021 as a data cut-off, 21 patients with various tumor types have been enrolled and treated. Among included patients, 11 (52.4%) had ALK mutations or amplification and 10 patients (47.6%) had ALK rearrangements with or without other ALK alterations. Patients received a median of 2 (range, 1-5) prior lines of therapy.
In 10 patients with ALK rearrangements, there were 3 PRs (30.0%) in one patient with melanoma, papillary urothelial carcinoma, and colon adenocarcinoma each and fusion gene partners in those tumors were EMILIN1, DCTN1, and DIAPH2; a median DoR was 6.8 months. Additionally, 3 patients (with colon adenocarcinoma, uterine leiomyosarcoma, and pancreatic adenocarcinoma) in this group had SD longer than 4 months, one of those had also ALK amplification, and fusion gene partners were STRN, IGFBP5, and EML4; DCR was 60.0%. However, there were no responses among the 11 patients with ALK mutations or amplification.
Confirmed ORR for the entire group was 14.3% (in 3 of 21 patients), and DCR was 42.9% (in 9 of 21 patients). Median PFS was 8.2 months in patients with ALK rearrangements versus 1.8 months in those with other ALK alterations.
Alectinib-related adverse events were observed in 85.7% of patients, with 3 (14.3%) experiencing grade 3 adverse events (anemia, hypokalaemia, and changes in AST, ALT, and/or blood creatinine levels). Adverse events were consistent with the known alectinib safety profile.
The authors concluded that although the number of included patients was small, alectinib showed activity in patients with ALK-rearranged advanced solid tumors, other than NSCLC.
My Pathway: A Study Evaluating Herceptin/Perjeta, Tarceva, Zelboraf/Cotellic, Erivedge, Alecensa, and Tecentriq Treatment Targeted Against Certain Molecular Alterations in Participants With Advanced Solid Tumors – NCT02091141
 Swanton C, Friedman CF, Sweeney CJ, at al. Activity and safety of alectinib for ALK-altered solid tumors from MyPathway. Presented at 2022 AACR Annual Meeting (April 8 – 13). In: Proceedings of the 113th Annual Meeting of the American Association for Cancer Research; 2021 April 8-13; New Orleans LA. Philadelphia (PA): AACR; 2022. Abstract nr CT032.
Featured image: The American Association for Cancer Research (AACR) Annual Meeting in pre-COVID19 Days: New Orleans, LA – The AACR 2016 Annual Meeting. Photo courtesy AACR/Scott Morgan.