186P - Pooled efficacy and safety data of alectinib (A) vs. crizotinib (C) from the randomized phase III ALEX and J-ALEX trials

Background

Among patients (pts) with ALK+ advanced non-small cell lung cancer (NSCLC) naïve to ALK-inhibitors, A significantly prolonged progression-free survival (PFS) over C. We present results of a post-hoc patient-level pooled analysis at interim data cut-off of the randomized phase III trials ALEX (NCT02075840) and J-ALEX (JapicCTI-132316), exploring new prognostic factors.

Methods

In both studies, the primary endpoint was PFS by RECIST v1.1. Treatment crossover was only allowed in the J-ALEX trial. Multivariate analysis was performed by Cox’s model, the independence of the two trial data sets was managed by random effects models. Survival outcomes were correlated with baseline characteristics including high tumor burden (hTB, i.e. > median sum of diameter of target lesions) and body mass index (BMI).

Results

The pooled set included 500 pts (A=249, C=251) with data available for survival and safety analysis. There was no imbalance between A and C groups in age (median 58 vs 56), sex (female 58% vs 59%), brain metastases (29% vs 34%), BMI (<25 70% vs 67%). At a median follow-up of 17.1 months, A provided prolonged PFS over C (median not reached vs. 10.2 months, HR 0.41, 95% CI 0.31-0.55, p<0.001), with median OS not reached in any arm (HR 0.80, 95% 0.50-1.28, p=0.353). In the multivariate analysis with correction for ethnicity, hTB (>55mm) was linked to worse PFS regardless of the treatment received (HR 1.66, 95% CI 1.26-2.20, p<0.001), and BMI ≥25 was correlated with better OS compared to BMI <25 (HR 0.50, 95% 0.29-0.88, p=0.025). Treatment effectiveness in subgroups is shown in table. Significant interaction between treatment and TB (p=0.002) was found in subgroup PFS analysis. Grade ≥3 adverse events occurred in 36% of pts with A vs 51% with C, 15% of pts discontinued A vs 20% C. Table: 186P

Subgroup analysis

Conclusions

hTB is a prognostic and predictive factor in patients with advanced ALK+ NSCLC under ALK-inhibitors, while a BMI ≥25 is linked to a reduced risk of death. Escalation strategies could be explored for hTB.

Clinical trial identification

This is a pooled analysis of ALEX (NCT02075840) and J-ALEX (JapicCTI-132316) trials. This abstract is based on research using data from data contributor F. Hoffmann–La Roche that has been made available through Vivli, Inc. Vivli has not contributed to or approved, and is not in any way responsible for, the contents of this publication.

Editorial acknowledgement

Legal entity responsible for the study

Marco Tagliamento (Study PI) and IRCCS Policlinico San Martino Hospital.

Funding

Has not received any funding.

Disclosure

M. Tagliamento: Non-Financial Interests, Member, International Lung Cancer Foundation Fellow: IASLC; Non-Financial Interests, Member, Lung Cancer Group: EORTC; Other, Travel and accommodation expenses: Eli Lilly. C. Genova: Financial Interests, Personal, Invited Speaker, Speaker's Bureau (scientific meeting): AstraZeneca, Bristol Myers Squibb, Merck-Sharp-Dohme, Eli Lilly, Novartis; Financial Interests, Personal, Advisory Board, Advisory board: Amgen, Sanofi; Financial Interests, Personal, Advisory Board, Advisory Board: Roche, Takeda; Financial Interests, Institutional, Funding, Funding for support of translational study: Bristol Myers Squibb; Financial Interests, Institutional, Funding, Funding in support of translational study: AstraZeneca; Financial Interests, Institutional, Research Grant, Research Grant for translational study: Italian Ministry of Health; Non-Financial Interests, Principal Investigator, Local PI for clinical trials: AstraZeneca, Roche; Non-Financial Interests, Member, Scientific society membership: ASCO, AIOM, FONICAP, AIOT, IASLC, ISLB. E. Blondeaux: Financial Interests, Institutional, Research Grant, Research grant to my Institution for a research project: Gilead Science. M. Brandão: Financial Interests, Personal, Invited Speaker, Speaker at a symposium at the AORTIC Conference 2019 : Roche; Financial Interests, Institutional, Invited Speaker, December 2021 : Janssen; Financial Interests, Institutional, Advisory Board, 03/2023: Sanofi; Financial Interests, Institutional, Invited Speaker, 01/2023: Takeda; Financial Interests, Institutional, Invited Speaker, 05/2023: Pfizer; Financial Interests, Institutional, Local PI: AstraZeneca, Roche, Boehringer Ingelheim, Sanofi; Non-Financial Interests, Leadership Role, EORTC Lung Cancer Group - Young and Early Career group Chair (since January 2022): EORTC. J. Remon Masip: Financial Interests, Personal, Invited Speaker: Roche, MSD, Boehringer Ingelheim; Financial Interests, Personal, Writing Engagement: Pfizer; Financial Interests, Personal, Advisory Board: AstraZeneca, OSE Immunotherapeutics, BMS, Jansse, Takeda, Sanofi; Financial Interests, Institutional, Invited Speaker: Merck Portugal; Non-Financial Interests, Principal Investigator, PI of PECATI trial in Thymic malignancies endorsed by a grant by MSD: MSD; Non-Financial Interests, Other, Co-PI of APPLE trial (EORTC-1525): AstraZeneca; Non-Financial Interests, Member, Secretary of the Lung Cancer Group at the EORTC: EORTC. L. Del Mastro: Financial Interests, Personal, Invited Speaker, Educational meeting: Novartis, Symposia, Andromeda E20, Vyvamed srl; Financial Interests, Personal, Invited Speaker, Lecture: Ipsen; Financial Interests, Personal, Advisory Board, Her2+ and TN breast cancer: Roche; Financial Interests, Personal, Writing Engagement, Consultancy for TNBC text: Roche; Financial Interests, Personal, Advisory Board, denosumab: Amgen; Financial Interests, Personal, Advisory Board, Early and metastatic BC: Eli Lilly; Financial Interests, Personal, Invited Speaker, CDK4-6 inhibitors: Eli Lilly; Financial Interests, Personal, Advisory Board, tucatinib: Seagen Int; Financial Interests, Personal, Advisory Board, Oncotype dx: Exact sciences, Havas life; Financial Interests, Personal, Advisory Board, Neratinib: Pierre Fabre; Financial Interests, Personal, Invited Speaker, Internal training: MSD; Financial Interests, Personal, Invited Speaker, Educational meetings: Accademia Nazionale Medicina; Financial Interests, Personal, Writing Engagement, Author for BC text: Pensiero Scientifico Editore; Financial Interests, Personal, Advisory Board, Breast cancer: Uvet; Financial Interests, Personal, Other, Author slide kits and interviews: Think2it; Financial Interests, Personal, Advisory Board, Palbociclib: Pfizer; Financial Interests, Personal, Invited Speaker, Breast cancer: Aristea, Meeting SrL; Financial Interests, Personal, Other, Author slide kits: Forum service; Financial Interests, Personal, Other, Author text about biosimilars: Edizioni Minerva Medica; Financial Interests, Personal, Other, consultant: Kardo srl; Financial Interests, Personal, Invited Speaker, Breast cancer meetings: Delphi international, Over srl; Financial Interests, Personal, Invited Speaker: Prex Srl, Editree; Financial Interests, Personal, Advisory Board: Uvet, Collage SpA, Daiichi Sankyo, AstraZeneca, Agendia, Gilead; Financial Interests, Personal, Other, Interview: Infomedica srl; Financial Interests, Personal, Other, Consultant: Sharing progress in cancer care - Switzerland; Financial Interests, Personal, Other, Consultancy: Eli Lilly; Financial Interests, Institutional, Funding, National coordinating PI: Roche; Financial Interests, Institutional, Funding, Local PI: AstraZeneca, Roche, Eli Lilly, Daiichi Sankyo, Novella Clinical, Novartis; Non-Financial Interests, Institutional, Product Samples, Genomic Test: FoundationOne. L. Hendriks: Financial Interests, Institutional, Advisory Board: Amgen, Boehringer Ingelheim, Lilly, Novartis, Pfizer, Takeda, BMS, Merck, Janssen, MSD; Financial Interests, Personal, Other, mentorship with key opinion leaders funded by AstraZeneca: AstraZeneca; Financial Interests, Institutional, Invited Speaker, for educational webinar: AstraZeneca, Lilly; Financial Interests, Institutional, Invited Speaker, educational webinar/interview: Bayer; Financial Interests, Institutional, Invited Speaker, educationals: MSD; Financial Interests, Personal, Invited Speaker, for webinars: Medtalks; Financial Interests, Institutional, Advisory Board, one time also personal: Roche; Financial Interests, Institutional, Other, performing interviews at conference: Roche; Financial Interests, Personal, Other, travel support: Roche; Financial Interests, Institutional, Other, podcast on brain metastases: Takeda; Financial Interests, Personal, Invited Speaker, payment for post ASCO round table discussion: VJOncology; Financial Interests, Personal, Invited Speaker, payment for post ASCO/ESMO/WCLC presentations, educational committee member: benecke; Financial Interests, Institutional, Invited Speaker, payment for post ESMO/ASCO discussion: high5oncology; Financial Interests, Institutional, Other, educational webinar: Janssen; Financial Interests, Personal, Other, member of the committee that revised these guidelines: Dutch guidelines NSCLC, brain metastases and leptomeningeal metastases; Financial Interests, Institutional, Research Grant, for IIS: Roche, Boehringer Ingelheim, AstraZeneca, takeda; Financial Interests, Institutional, Local PI: AstraZeneca, GSK, Novartis, Merck Serono, Roche, Takeda, Blueprint Medicines, Mirati, AbbVie, MSD, Gilead; Financial Interests, Institutional, Research Grant, donation for health care improvement project: Merck; Financial Interests, Institutional, Research Grant, funding for healthcare improvement project: Pfizer; Non-Financial Interests, Other, Chair metastatic NSCLC for lung cancer group: EORTC; Non-Financial Interests, Other, secretary NVALT studies foundation: NVALT. F. Barlesi: Financial Interests, Institutional, Advisory Board: AstraZeneca, Bayer, Bristol Myers Squibb, Boehringer Ingelheim, Eli Lilly Oncology, F. Hoffmann–La Roche Ltd, Novartis, Merck, Mirati, MSD, Pierre Fabre, Pfizer, Sanofi Aventis, Seattle Genetics, Takeda, AbbVie, ACEA, Amgen, Eisai, Ignyta; Non-Financial Interests, Principal Investigator: AstraZeneca, BMS, Merck, Pierre Fabre, F. Hoffmann-La Roche Ltd., Innate Pharma, Mirati. D. Planchard: Financial Interests, Personal, Advisory Board: AstraZeneca, BMS, Merck, Novartis, Pfizer, Roche, Samsung, Celgene, AbbVie, Daiichi Sankyo, Janssen, Seagen, Gilead, Pierre Fabre; Financial Interests, Personal, Invited Speaker: AstraZeneca, Novartis, Pfizer, priME Oncology, Peer CME, Samsung, AbbVie, Janssen; Non-Financial Interests, Principal Investigator, Institutional financial interests: AstraZeneca, BMS, Merck, Novartis, Pfizer, Roche, Daiichi Sankyo, Sanofi-Aventis, Pierre Fabre; Non-Financial Interests, Principal Investigator: AbbVie, Sanofi, Janssen. M. Lambertini: Financial Interests, Personal, Advisory Board: Roche, AstraZeneca, Lilly, Novartis, Pfizer, Exact Sciences, MSD, Seagen, Gilead; Financial Interests, Personal, Invited Speaker: Takeda, Sandoz, Ipsen, Libbs, Knight, Daiichi Sankyo, Lilly, Pfizer, Novartis, Roche; Financial Interests, Personal, Other, Travel grant to attend ASCO 2022: Gilead; Financial Interests, Institutional, Coordinating PI, 2-year research grant paid to my Institution: Gilead. B. Besse: Financial Interests, Institutional, Funding: 4D Pharma, AbbVie, Amgen, Aptitude Health, AstraZeneca, BeiGene, Blueprint Medicines, Boehringer Ingelheim, Celgene, Cergentis, Cristal Therapeutics, Daiichi Sankyo, Eli Lilly, GSK, Janssen, Onxeo, OSE immunotherapeutics, Pfizer, Roche-Genentech, Sanofi, Takeda, Tolero Pharmaceuticals; Financial Interests, Institutional, Research Grant: Genzyme Corporation, Chugai pharmaceutical, EISAI, Inivata, IPSEN, Turning Point Therapeutics. All other authors have declared no conflicts of interest.