98P - Retrospective indirect comparison of alectinib phase II data vs ceritinib real-world data in ALK+ NSCLC after progression on crizotinib

Date 07 May 2017
Event ELCC 2017
Session Poster Display Session
Topics Immunotherapy
Thoracic Malignancies
Non-Small Cell Lung Cancer
Presenter Jessica Davies
Citation Annals of Oncology (2017) 28 (suppl_2): ii28-ii51. 10.1093/annonc/mdx091
Authors J. Davies1, M. Martinec2, R. Martina3, P. Delmar2, M. Coudert4, W. Bordogna2, S. Golding2, G. Crane5
  • 1Roche Products Ltd., AL7 1TW - Welwyn/GB
  • 2F. Hoffmann-La Roche Ltd., Basel/CH
  • 3Translational Medicine, Liverpool/GB
  • 4F. Hoffmann-La Roche Ltd., Boulogne-Billancourt Cedex/FR
  • 5Roche Products Ltd., Welwyn/GB



Approvals of second-line ALK inhibitors (ALKi) ceritinib and alectinib are based on single-arm trials that lack comparative efficacy data to support health technology assessments. We assessed if real-world data (RWD) could provide this by acting as an external control for single-arm studies by comparing data generated from alectinib trials and ceritinib patient data.


We retrospectively analysed patients (pts) with ALK+ advanced NSCLC receiving an ALKi after crizotinib failure. The alectinib arm (ALC; n = 183) included pts from the phase II NP28673/NP28761 studies. To generate the ceritinib control arm (CER; n = 67) eligibility criteria similar to the alectinib trials was applied to the Flatiron Health’s electronic health record database. A propensity score based on prognostic factors was generated and applied by inverse probability treatment weighting. A multivariate Cox model was used to evaluate the association of ALC compared with CER on overall survival (OS) adjusting for age, sex, prior treatment, race and stage at diagnosis. Summary data from the CER trial ASCEND-2 were re-digitised to compare with CER RWD.


Prior to re-weighting, the arms were heavily imbalanced. Key differences between the arms included age, prior treatments and baseline CNS metastases (median: 53 vs 61 yrs, 36% vs 13% [≥3 lines], 61% vs 35%, ALC vs CER). After weighting, balance was achieved across all key prognostic factors with a standardised mean difference <10% for all factors. A multivariate Cox model showed ALC was associated with lower risk of death (HR 0.65; 95% CI 0.48–0.88). Adjusted median OS was 24.2 months for ALC (95% CI 17.5–NR) vs 15.6 months for CER (95% CI 15.5–18.6). Median OS in the RWD CER group was similar to that reported in the CER ASCEND-2 trial (14.9 months).


The results show that ALC is associated with prolonged OS vs CER, which was consistent through numerous sensitivity analyses. CER RWD median OS was similar to that observed in ASCEND 2, validating this analysis. For single-arm studies, RWD can serve as an external control for producing comparative data.

Clinical trial identification

NP28673 NP28761

Legal entity responsible for the study

F. Hoffmann-La Roche


F. Hoffmann-La Roche


J. Davies, G. Crane: Employee at Roche Products Ltd. P. Delmar, M. Coudert: Employee at F. Hoffmann-La Roche, Ltd. M. Martinec, W. Bordogna, S. Golding: Employee: F. Hoffmann-La Roche; Stock ownership: F. Hoffmann-La Roche. All other authors have declared no conflicts of interest.