Activity of Alectinib for ALK-Rearranged Metastatic Solid Tumours, Other Than NSCLC

In patients included in MyPathway, a multi-basket study assessing approved therapies in non-indicated advanced solid tumours with relevant alterations, alectinib showed activity in patients with ALKrearranged advanced solid tumours other than non-small cell lung cancer (NSCLC). As in NSCLC, cancers with ALK mutations or amplification were not responsive to ALK inhibition. Adverse events were consistent with the known alectinib safety profile. Findings were presented by Dr. Funda Meric-Bernstam of the University of Texas MD Anderson Cancer Center in Houston, TX, US on behalf of MyPathway colleagues at 2022 AACR Annual Meeting (8-13 April, New Orleans, US).

The study team analyzed alectinib activity and safety in a pan-tumour population with ALK alterations included in MyPathway study (NCT02091141). Enrolled patients were at least 18 years old and had metastatic tumours with ALK gene rearrangements, putative activating non-synonymous ALK mutations, and/or ALK gene amplification. All patients received alectinib.

The primary endpoint was investigator-assessed objective response rate (ORR) that comprised a complete response (CR) plus 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 tumour types have been enroled 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 tumours 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 for 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 (anaemia, 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 tumours, other than NSCLC.


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 (8-13 April, New Orleans, US).