1369P - BrigAlec study: Focus on alectinib efficacy after brigatinib exposure in BrigALK2 study (GFPC 02-2019)

Background

Brigatinib and alectinib are both next-generation ALK inhibitors (ALKi) showing efficacy in naïve and post-crizotinib ALK+ advanced non-small-cell lung cancer (aNSCLC). Real-life data on alectinib efficacy after brigatinib failure are missing.

Methods

BrigALK2 study retrospectively assessed the efficacy of brigatinib in 183 ALK ⁺ aNSCLC pretreated with at least one ALKi during the brigatinib French Early-Access Program (1 August 2016–21 January 2019). BrigAlec study made a focus on alectinib activity after brigatinib treatment, according to post-brigatinib treatment line in BrigALK2.

Results

92 (50.3%) patients received ≥ 1 agent(s) post-brigatinib. 30 (16.4%) received alectinib: 19 (10.3%) patients were treated with alectinib immediately after brigatinib, 11 (4.9%) following at least one line of treatment. At data cut-off, median follow up was 25.5 (95% CI: 10.6-30.5) months. Median duration of brigatinib treatment (mDOT) and median progression free survival according to investigator (InvmPFS) were 13.6 (95% CI: 6.3-17.7) and 10.9 (95% CI: 6.2-20.2) months, respectively. For patients who received alectinib immediately after brigatinib, mDOT was 7.1 (95% CI: 2.1-18.2) months, mInvPFS, 4.8 (95% CI: 2.0-12.5) months and mOS, 27 (95% CI: 12.5-NR) months from the start of alectinib treatment. Response (RR) and disease control rates (DCR) were 25% and 60%, respectively. Among this subgroup, reasons for brigatinib discontinuation were toxicity and progressive disease for 5 and 14 patients, respectively. mDOT and mPFS were 18.2 (95% CI: 3.4-21.6) and 12.5 (95% CI: 3.3-17.9) months for the former and 5.7 (95% CI: 0.9-10.6) and 3.4 (95% CI: 0.9-9.2) months for the latter, respectively. For patients receiving at least one treatment between brigatinib and alectinib, with a median follow up of 13.3 (95% CI: 2.3-31.5) months, mDOT, mInvPFS and mOS were 11.7 (95% CI: 0.7-21.5), 5.0 (95% CI: 0.5-18.8) and 16 (95% CI: 2.3-NR) months, respectively. RR and DCR were 10 and 30.

Conclusions

According to our retrospective real-life study, alectinib after brigatinib treatment remains an option in metastatic ALK+ NSCLC, especially if brigatinib is discontinued due to toxicity.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

GFPC (Groupe Français de Pneumo-Cancérologie): French Lung Cancer Group.

Funding

Takeda.

Disclosure

R. Descourt: Financial Interests, Personal, Advisory Board: Takeda, AstraZeneca, BMS, Pfizer. F. Guisier: Financial Interests, Personal, Advisory Board: AstraZeneca, Roche, BMS, Sanofi, Amgen, MSD; Financial Interests, Institutional, Research Funding: Roche, Pfizer, Takeda. M. Pérol: Financial Interests, Personal, Advisory Board: Roche, AstraZeneca, MSD, BMS, Lilly, Novartis, Takeda, Gritstone, Sanofi, Pfizer, Amgen, Janssen, Gsk, Eisai, Ipsen; Financial Interests, Personal, Invited Speaker: Roche, AstraZeneca, MSD, BMS, Boehringer Ingelheim, Takeda, Illumina, Pfizer, Medscape; Financial Interests, Institutional, Research Grant: AstraZeneca, Roche, Takeda, Boehringer Ingelheim; Financial Interests, Personal, Steering Committee Member: Roche; Financial Interests, Personal, Other, DMSB: Roche. J. Cadranel: Financial Interests, Personal, Advisory Board, Participation to boards: Amgen, Daiichi, Takeda, MSD, Jansen, AZ; Financial Interests, Institutional, Other, prospective: AbbVie; Non-Financial Interests, Principal Investigator, Trials: AZ, AbbVie, Takeda, BI, Daiichi, Pfizer, Novartis, Amgen, Sanofi, Jansen, BMS; Financial Interests, Institutional, Research Grant, Translational research: AbbVie; Financial Interests, Institutional, Research Grant, Preclinical research: Sanofi; Financial Interests, Institutional, Research Grant, Support to academic trial: Pfizer; Financial Interests, Personal, Advisory Board, Participation to Boards: Pfizer; Financial Interests, Institutional, Advisory Board, Participation to boards: Novartis, Sanofi; Financial Interests, Personal, Invited Speaker, Participation to boards: BI. M. Duruisseaux: Financial Interests, Personal, Advisory Board: Takeda, Roche, BMS, GSK, Amgen, MSD, Janssen, AstraZeneca, Elevation oncology, Lilly; Financial Interests, Institutional, Research Funding: Lilly. H. Doubre: Financial Interests, Personal, Advisory Board: Amgen; Financial Interests, Personal, Invited Speaker: Léo Pharma; Financial Interests, Institutional, Local PI: BMS, Merck. C. Lamour: Financial Interests, Personal, Advisory Board: Takeda, AstraZeneca, MSD, Sanofi. D. Moro-Sibilot: Financial Interests, Personal, Advisory Board: Lilly, Roche, BMS, MSD, Abbvie, Becton Dickinson, Pfizer, Takeda, AstraZeneca, Boehringer Ingelheim, Novartis, GSK, Sanofi; Financial Interests, Personal, Invited Speaker: Amgen; Financial Interests, Institutional, Funding, IFCT clinical trials: Pfizer; Financial Interests, Institutional, Funding: Roche, Abbvie, AstraZeneca. B. Mennecier: Financial Interests, Personal, Advisory Board: BMS, MSD, AstraZeneca, Sanofi, Pfizer, Lilly, Novartis, Takeda, Boehringer; Financial Interests, Personal, Invited Speaker: Roche. N. Martin: Financial Interests, Personal, Advisory Board: AstraZeneca. O. Bylicki: Financial Interests, Personal, Advisory Board, Expert Board: BMS, Roche, Takeda; Financial Interests, Personal, Advisory Board, Annuel contrat: MSD; Financial Interests, Personal, Advisory Board, expert board: AstraZeneca, Janssen. C. Chouaid: Financial Interests, Personal, Advisory Board: AZ, BI, GSK, Roche, Sanofi Aventis, BMS, MSD, Lilly, Novartis, Pfizer, Takeda, Bayer, Janssen and Amgen; Financial Interests, Institutional, Funding: AZ, BI, GSK, Roche, Sanofi Aventis, BMS, MSD, Lilly, Novartis, Pfizer, Takeda, Bayer, Janssen and Amgen. L. Greillier: Financial Interests, Personal, Advisory Board: AbbVie, AstraZeneca, BMS, MSD, Novartis, Sanofi, Takeda, Roche; Financial Interests, Personal, Invited Speaker: Lilly, Pfizer; Financial Interests, Institutional, Local PI: AstraZeneca, AbbVie, BMS, MSD, Novartis, Takeda, Pfizer, PharmaMar; Financial Interests, Institutional, Coordinating PI: Sanofi; Financial Interests, Personal, Local PI: Roche. All other authors have declared no conflicts of interest.