105P - Prognostic factors in crizotinib (CRZ)-resistant anaplastic lymphoma kinase (ALK+) non-small cell lung cancer (NSCLC) patients (Pts)

Date 07 May 2017
Event ELCC 2017
Session Poster Display Session
Topics Non-Small-Cell Lung Cancer, Locally Advanced
Non-Small-Cell Lung Cancer, Metastatic
Cancer Immunology and Immunotherapy
Lung and other Thoracic Tumours
Presenter Karen Reckamp
Citation Annals of Oncology (2017) 28 (suppl_2): ii28-ii51. 10.1093/annonc/mdx091
Authors K.L. Reckamp1, J. Lee2, J. Huang3, I. Proskorovsky4, W. Reichmann3, M. Krotneva4, D. Kerstein3, H. Huang3
  • 1City of Hope Comprehensive Cancer Center, 91010 - Duarte/US
  • 2Evidera, San Francisco/US
  • 3ARIAD Pharmaceuticals Inc., Cambridge/US
  • 4Evidera, Montreal/CA

Abstract

Background

The aim of this analysis was to assess prognostic factors in patients with CRZ-resistant ALK+ NSCLC associated with progression-free survival (PFS), overall survival (OS), and objective response rate (ORR) based on the Phase 2 ALTA Trial (NCT02094573) of brigatinib.

Methods

Analyses used data from ALTA Arm B (180 mg qd with a 7-day lead-in at 90 mg, N = 110). Potential prognostic factors were evaluated using univariate and multivariate Cox proportional hazards models for PFS and OS, and logistic regression for ORR. Potential prognostic factors included age, sex, race, ECOG performance status, prior radiotherapy (RT), prior RT to brain, prior chemotherapy, prior platinum-based chemotherapy, smoking status, number of prior regimens, best response to prior CRIZ, number of metastatic sites, and active brain lesions. ALTA trial was not powered to detect differences in outcomes by these factors, thus a threshold of p < 0.5 was used to select variables into all models. Factors with hazard ratios >1.30 or < 0.77 were also included in the final models for PFS and OS.

Results

As of February 29, 2016, median follow-up was 8.3 months, and independent review committee (IRC) assessed median PFS was 15.6 months [95% CI: 11.0, NR] (31 events). Median OS was not reached (17 deaths). IRC-assessed ORR was 52.7% [95% CI: 43.0%, 62.3%]. Prognostic factors are shown in the table.rnTable: 105P

Important prognostic factors in CRIZ-resistant ALK+ NSCLC treated with brigatinib 180 mg qd with a 7-day lead-in at 90 mg (N = 110)

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Prognostic FactorPFS (HR [95% CI])*OS (HR [95% CI])*ORR (OR [95% CI])**
Age (per 1-year increase)0.98 [0.95, 1.01]
Sex Male vs female1.79 [0.84, 3.79]
Race Asian vs non-Asian1.29 [0.55, 3.04]0.15 [0.02, 1.25]1.87 [0.73, 5.00]
ECOG performance status 1 vs 0 2 vs 00.72 [0.33, 1.58] 3.24 [0.99, 10.60]2.56 [0.72, 9.06] 4.02 [0.73, 22.14]0.64 [0.26, 1.53] 0.19 [0.02, 1.07]
Prior chemotherapy Yes vs no0.42 [0.19, 0.95]0.34 [0.11, 1.04]1.90 [0.71, 5.24]
Best response to prior CRIZ CR/PR vs any other status or unknown0.56 [0.25, 1.27]0.74 [0.24, 2.33]1.88 [0.77, 4.70]
Prior radiotherapy to brain Yes vs no2.21 [1.02, 4.78]0.51 [0.17, 1.57]
Active brain lesions Yes vs no0.45 [0.15, 1.39]
Smoking status Never vs current/former/unknown0.49 [0.14, 1.67]2.45 [1.04, 5.97]
Number of metastatic sites 3 vs 1-2 4+ vs 1-21.05 [0.20, 5.58] 2.66 [0.59, 12.03]0.34 [0.10, 1.08] 0.81 [0.27, 2.36]
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Abbreviations: PFS = progression-free survival; OS = overall survival; ORR = objective response rate; HR = hazard ratio; OR = odds ratio; CI = confidence interval; CR = complete response; PR = partial response; ECOG = Eastern Cooperative Oncology Group;

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HR < 1 indicates lower risk of progression or death vs reference group;

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OR > 1 indicates higher odds of response vs reference group

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Conclusions

In this analysis of CRZ-resistant ALK+ NSCLC patients, a history of prior chemotherapy was associated with longer PFS, while prior radiotherapy was associated with shorter PFS, both likely due to unmeasured patient characteristics. Never smokers had more than double the odds of response, versus current or former smokers. ECOG status 2 was nominally associated with shorter PFS and OS and lower ORR, and presence of active brain lesions was associated with longer OS.

Clinical trial identification

The trial protocol number is NCT02094573.

Legal entity responsible for the study

Evidera Inc.

Funding

ARIAD Pharmaceuticals

Disclosure

K.L. Reckamp: Consulting or advisory role (ARIAD), research funding (ARIAD). J. Lee, M. Krotneva: Employee of Evidera Inc., which provides consulting services to pharmaceutical organizations. Evidera Inc. received funding from ARIAD pharmaceuticals. J. Huang: Employment, consulting or advisory role (ARIAD). W. Reichmann, D. Kerstein, H. Huang: Employment, stock shareholder (ARIAD). All other authors have declared no conflicts of interest.