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.