P3.103 | Efficacy of Crizotinib in Retrospective Comparisons with Standard-Of-Care (SOC) Regimens from Three Pfizer-Sponsored Clinical Trials in Patients with Advanced Non-Small Cell Lung Cancer (NSCLC)
Y. Tang, B. Huang, K. Wilner, P. Selaru
Pfizer Oncology,/UNITED STATES OF AMERICA
Background:
Crizotinib is a potent, selective, ATP-competitive, small-molecule anaplastic lymphoma kinase (ALK) inhibitor. In an expanded cohort of an early clinical study in patients with advanced ALK+ NSCLC, crizotinib demonstrated clinical activity with a high response rate. Results of retrospective analyses comparing the efficacy of crizotinib in patients with advanced NSCLC with that of SOC regimens (paclitaxel/carboplatin or gemcitabine/cisplatin as first-line treatment and erlotinib as second-/third-line treatment) in three Pfizer-sponsored clinical trials are reported.
Methods:
We conducted two types of analysis: (1) covariate-matched simulations of randomized controlled trials of crizotinib versus SOC for advanced NSCLC from control arms of the three Pfizer-sponsored trials to compare efficacy outcomes in patients with comparable baseline characteristics (adenocarcinoma histology, smoking classification, age, and race [Asian/non-Asian]), and (2) a covariate-adjusted modeling analysis to retrospectively predict the response rates of patients treated with crizotinib who had the same baseline characteristics (adenocarcinoma histology, smoking classification, age, race [Asian/non-Asian], gender, disease stage, ECOG performance status, and weight) as those treated with a SOC regimen from a control arm in the three Pfizer-sponsored trials. Information about ALK status was not available from the three control trials.
Results:
Crizotinib therapy was associated with a higher objective response rate (ORR; 61%; 95% confidence interval [CI]: 52, 70%) than ORRs of the covariate-matched unselected historical controls from the three Pfizer-sponsored trials, ranging from 10% to 24%. Similar results were observed using the covariate-adjusted modeling approach with estimated ORRs for the standard regimens ranging from 15% to 21% after simultaneous adjustment for eight baseline characteristics. Overall, the estimated magnitudes of the ORRs generated for unselected controls using both approaches were at least 50% lower relative to the ORR of 61% observed with crizotinib. An assessment of the secondary endpoints, progression-free and overall survival (PFS; OS), produced similar results. The preliminary median PFS of crizotinib therapy was 10 months (95% CI: 8.2, 14.7 months) in heavily pretreated patients, which was longer than PFS reported in the covariate-matched unselected historical controls, ranging from 1.9 to 5.9 months. The hazard ratios for PFS of crizotinib versus each of the three control regimens ranged from 0.28 to 0.38. The median OS of crizotinib in the clinical trial has not yet been reached. However, the hazard ratios for OS of crizotinib versus the three control regimens ranged between 0.25 and 0.47.
Conclusion:
There is supporting evidence that crizotinib treatment may provide clinical benefit for the treatment of patients with ALK+ advanced NSCLC in the context of SOC therapies in first- or later-line treatment settings.
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