1298O_PR - Alectinib vs crizotinib in treatment-naïve ALK+ NSCLC: CNS efficacy results from the ALEX study

Date 11 September 2017
Event ESMO 2017 Congress
Session NSCLC, metastatic 2
Topics Anti-Cancer Agents & Biologic Therapy
Non-Small-Cell Lung Cancer, Metastatic
Lung and other Thoracic Tumours
Presenter Shirish Gadgeel
Citation Annals of Oncology (2017) 28 (suppl_5): v605-v649. 10.1093/annonc/mdx440
Authors S. Gadgeel1, S. Peters2, T. Mok3, A.T. Shaw4, D. Kim5, S.I. Ou6, M. Perol7, R. Dziadziuszko8, J.S. Ahn9, R. Rosell10, A. Zeaiter11, E. Mitry11, E. Nueesch11, B. Balas11, R. Camidge12
  • 11500e Medical Center Drive, University of Michigan, 48109 - Ann Arbor/US
  • 2Oncology, Lausanne University Hospital, Lausanne/CH
  • 3State Key Laboratory Of South China, Chinese University of Hong Kong, New Territories/HK
  • 4Cancer Center, Massachusetts General Hospital, Boston/US
  • 5Oncology, Seoul National University Hospital, Seoul/KR
  • 6Chao Family Comprehensive Cancer Center, University of California, Irvine School of Medicine, Orange/US
  • 77department Of Medical Oncology, Centre Léon Bérard, 69008 - Lyon/FR
  • 8Department Of Oncology And Radiotherapy, Medical University of Gdansk, Gdansk/PL
  • 9Division Of Hematology-oncology, Departments Of Internal Medicine, Samsung Medical Center Sungkyunkwan University School of Medicine, Seoul/KR
  • 10Oncology, Catalan Institute of Oncology, Badalona/ES
  • 11Oncology, F. Hoffmann-La Roche Ltd., Basel/CH
  • 12Oncology, University of Colorado Hospital, Denver/US



ALEX phase III study (NCT02075840) of alectinib (ALC) vs crizotinib (CRZ) in treatment-naïve advanced ALK+ NSCLC, met its primary endpoint of improved progression-free survival (PFS). Pts with asymptomatic brain mets at baseline (BL), treated with radiotherapy (RT) or not, were eligible. We present comprehensive CNS efficacy data.


Pts aged ≥18 years were randomized 1:1 to ALC 600mg or CRZ 250mg (both twice daily) until disease progression (PD), toxicity, withdrawal or death. CNS MRIs were done at BL and every 8 wks in all pts. An Independent Review Committee (IRC) assessed CNS endpoints (RECIST v1.1 and RANO). Endpoints (analysed by subgroup: pts with/without BL CNS disease; pts with/without prior RT) included patterns of PD, CNS objective response rates (CORR), CNS PD and PFS.


Overall, 303 pts were randomised (ALC n = 152; CRZ n = 151); 122 had BL CNS mets by IRC (ALC n = 64 [42%]; CRZ n = 58 [38%]), of whom 43 had IRC-assessed measurable lesions (ALC n = 21; CRZ n = 22); 47/122 pts had received prior RT (ALC n = 26 [62% WBRT]; CRZ n = 21 [71% WBRT]). Subgroup analyses of PFS and CNS PD are in Table 1. In the CRZ arm first PD was more common in CNS than in non-CNS sites in pts with (CNS PD 57% vs non-CNS PD 24%) and without (CNS PD 38% vs non-CNS PD 20%) CNS mets at BL. In the ALC arm first PD was more common in non-CNS sites in pts without CNS mets at BL (CNS PD 6.8% vs non-CNS PD 28%); first PD in CNS and non-CNS was similar in pts with CNS mets at BL (CNS PD 19% vs non-CNS PD 17%). CORR (RECIST) in pts with measurable CNS mets at BL was ALC 85.7% vs CRZ 71.4% for pts with prior RT and ALC 78.6% vs CRZ 40.0% for pts without RT. In pts with measurable and non-measurable CNS mets at BL, CORR was ALC 36.0% vs CRZ 28.6% for pts with prior RT, and ALC 74.4% vs CRZ 24.3% for those without. Data by RANO criteria will be presented.Table:

1298O_PR Subgroup analysis of PFS and CNS PD§

Pts without CNS disease at BL (IRC)Pts with CNS disease at BL (IRC)
All patientsPts who had received prior RTPts who had not received prior RT
ALC N = 88CRZ N = 93ALC N = 64CRZ N = 58ALC N = 25*CRZ N = 21ALC N = 39CRZ N = 37
Median PFS by INV, months (95% CI)NE (NE)14.8 (10.8–20.3)NE (9.2–NE)7.4 (6.6–9.6)NE (11.0–NE)12.7 (7.2–14.6)14.0 (5.6–NE)7.2 (3.9–8.6)
HR (95% CI) P value 0.51 (0.33–0.80)0.40 (0.25–0.64) 0.34 (0.15–0.78) 0.44 (0.25–0.78)
p = 0.0024p 


ALC showed significantly superior CNS activity vs CRZ in previously untreated advanced ALK+ NSCLC, irrespective of prior RT, and had a protective effect in the CNS.

Clinical trial identification


Legal entity responsible for the study

F. Hoffmann-La Roche Ltd.


F. Hoffmann-La Roche Ltd.


S. Gadgeel: Consulting fees from Boehringer Ingelheim, ARIAD, Novartis, Genentech, Pfizer and AstraZeneca during the conduct of the study. S. Peters: Grants and personal fees from Amgen, AstraZeneca, Boehringer-Ingelheim, Bristol-Myers Squibb, Clovis, Eli Lilly, Roche, Guardant health, Janssen, Merck Sharp and Dohme, Merck Serono, Merrimack, Morphotek, Pfizer, Regeneron and Takeda. T.S.K. Mok: Personal fees: AZ, MSD, Novartis, BI, Pfizer, Roche/Genentech, BMS, Eli Lilly, Eisai, SFJ, Clovis, Taiho, Merck Serono, Celgene, OncoGenex Technologies, ACEA Biosciences, Vertex, Ignyta, Cirina, GeneDecode., Ariad/Tekeda. Stock ownership: Sanomics. A.T. Shaw: Personal fees from Genentech/Roche, Pfizer, Novartis, Genentech/Roche, Ariad, Ignyta, Daiichi-Sankyo, Taiho, Blueprint Medicines, Loxo, EMD Serono and Foundation Medicine. S-H.I. Ou: Personal fees from Pfizer, Roche, Astra Zeneca, ARIAD, Ignyta and Foundation Medicine. M. Perol: Personal fees from Roche, Lilly, BMS, Novartis, Astra-Zeneca, Boehringer-Ingelheim, Clovis Oncology, Merck, Pfizer, Pierre Fabre, Amgen. R. Dziadziuszko: Personal fees from Roche, Novartis, Tesaro, Clovis, Pfizer, Boehringer-Ingelheim, Ignyta and Astra-Zeneca. J.S. Ahn: Personal fees from BMS, Eisai, Janssen, Roche, Menarini and Boehringer Ingelheim. A. Zeaiter, E. Mitry, E. Nueesch: Full-time employee at F. Hoffmann-La Roche Ltd. B. Balas: Full-time employee at F. Hoffmann-La Roche Ltd with stock ownership. R. Camidge: Personal fees from Roche Genetech, Genoptix, G1 Therapeutics, Orion, Clovis, Ariad, Novartis, Celgene, Array, Abbvie and Eli Lilly. All other authors have declared no conflicts of interest.