1209PD - Time to response in patients with ALK+ NSCLC receiving alectinib in the phase II NP28673 and NP28761 studies

Date 09 October 2016
Event ESMO 2016 Congress
Session NSCLC, metastatic
Topics Anticancer Agents
Non-Small Cell Lung Cancer
Biological Therapy
Presenter Leena Gandhi
Citation Annals of Oncology (2016) 27 (6): 416-454. 10.1093/annonc/mdw383
Authors L. Gandhi1, S. Gadgeel2, A. Shaw3, F. Barlesi4, L. Crinò5, J.C. Yang6, A.C. Dingemans7, D. Kim8, F. de Marinis9, M. Schulz10, S. Liu10, S. Fish10, A. Kotb11, S.I. Ou12
  • 1Medical Oncology, Dana Farber Cancer Institute, 02284-9168 - Boston/US
  • 2Wayne State University, Karmanos Cancer Institute, Detroit/US
  • 3Massachusetts General Hospital Cancer Center, Massachusetts General Hospital, 02114 - Boston/US
  • 4Multidisciplinary Oncology & Therapeutic Innovations, Aix Marseille University, 13915 - Marseille/FR
  • 5Medical Oncology, Santa Maria della Misericordia Hospital, 06122 - Perugia/IT
  • 6Graduate Institute Of Oncology & Cancer Research Centre, National Taiwan University Hospital, 10617 - Taipei/TW
  • 7Pulmonology, MUMC, 6202 AZ - Maastricht/NL
  • 8Medical Oncology, Seoul National University Hospital, Seoul/KR
  • 9Thoracic Institute Of Oncology, European Institute of Oncology, Milano/IT
  • 10Us Medical Affairs, Genentech, Inc., San Francisco/US
  • 11Medical Affairs, F. Hoffmann-La Roche Ltd, Basel/CH
  • 12Medical Oncology, University of California at Irvine, Orange/US



Alectinib was approved by the FDA based on the efficacy and safety shown in two phase II studies (NP28673 [NCT01801111] and NP28761 [NCT01871805]) of patients (pts) with previously treated ALK+ non-small-cell lung cancer (NSCLC). Both studies showed that alectinib achieved high response rates (51% and 52%, respectively) and that responses were durable (median 14.1 mos and 13.5 mos, respectively) (Barlesi et al, ECC 2015; Shaw et al, WCLC 2015). This exploratory pooled analysis looked at the time to systemic response (TTR) and time to CNS response (TTCR) in both studies, to determine how rapidly patients can benefit from alectinib.


Pts (n = 225) ≥18 years with confirmed ALK+ NSCLC, which had progressed after prior crizotinib, received 600 mg oral alectinib twice daily. Restaging scans, including brain scans, were obtained every 8 wks (NP28673) or every 6 wks (NP28761) thereafter. Response was assessed by an independent review committee (IRC), according to RECIST v1.1. TTR and TTCR were defined as time from date of first dose to date of first occurrence of response in the response-evaluable population with confirmed response or in the safety population with confirmed CNS response, respectively.


Median follow-up was 14.5 mos (NP28673) and 9.9 mos (NP28761) (data cut-off 27 Apr 2015). Median TTRs and TTCRs by IRC for both studies are shown in the Table, including sub-analyses by baseline measurable (M) or non-measurable (NM) disease and no prior radiation (RT). Results were consistent between IRC and investigator assessment. In all populations, most pts who achieved a response did so by the first evaluation.


These data from the phase II alectinib studies suggest that alectinib can achieve a rapid response in patients, both systemically and in the CNS, with pts having RECIST response by first assessment in most cases. The ongoing phase III ALEX study will assess the efficacy of first-line alectinib vs crizotinib.

NP28673 (N = 138) NP28761 (N = 87)
Total no. of responders (no. responders by wk 8, wk 16) Median, wks (95% CI) Total no. of responders (no. responders by wk 6, wk 12) Median, wks (95% CI)
TTR in all responders 62 (44, 55) 8.0 (8.0–8.3) 35 (28, 31) 6.0 (5.9–6.1)
TTCR in M disease 20 (15, 17) 8.0 (7.9–10.3) 12 (9, 11) 6.0 (5.7–NE)
TTCR in M/NM disease 37 (26, 31) 8.1 (7.9–9.9) 21 (16, 20) 6.0 (5.7–11.0)
TTCR in M disease with no prior RT 6 (5, 5) 7.9 (7.9–NE) 5 (4, 5) 5.7 (5.7–NE)
TTCR in M/NM disease with no prior RT 12 (10, 10) 8.0 (7.9–NE) 12 (9, 12) 5.9 (5.7–NE)

NE = not estimable

Clinical trial identification

NP28673 [NCT01801111] and NP28761 [NCT01871805].

Legal entity responsible for the study

F. Hoffmann-La Roche Ltd


F. Hoffmann-La Roche Ltd


L. Gandhi: Honoraria for Merck, Consulting role for Merck, Genentech/Roche, AstraZeneca, Abbvie, Pfizer, Travel accommodation for Merck, BMS (grant recipient meeting)and Research funding from Bristol-Myers Squibb. S. Gadgeel: Advisory Board for Genentech/Roche, Pfizer, Ariad, Novartis. A. Shaw: Blueprint medicines Advisory board, Consulting for Genentech, Roche, Novartis, Pfizer, Ariad, Ignyta, Daiichi-sankyo, Taiho, EMD Serono. F. Barlesi: Roche Advisory board or board of directors and Corporate-sponsored research. J.C-H. Yang: Advisory board for Boehringer Ingelheim, Eli Lilly, Bayer, Roche/Genentech/Chugai, Astrazeneca, Astellas, MSD, Merck Serono, Pfizer, Novartis, Clovis Oncology, Celgene, innopharma, Merrimack. A-M.C. Dingemans: Advisory board or board of directors for Roche. D-W. Kim: Consulting or Advisory role for Novartis. M. Schulz: Roche Stock Ownership. S. Liu, S. Fish: Employee and Stock ownership in Genentech, Inc. A. Kotb: Employee of Roche. S-H.I. Ou: Roche Advisory Board, Roche Corporate sponsored research and Roche speakers bureau. All other authors have declared no conflicts of interest.