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Lung Cancer. 2017 Mar;105:7-13. doi: 10.1016/j.lungcan.2016.12.020. Epub 2016 Dec 31.

A randomized phase II study of LY2510924 and carboplatin/etoposide versus carboplatin/etoposide in extensive-disease small cell lung cancer.

Author information

1
Department of Medicine, The University of Chicago, Chicago, IL, United States. Electronic address: rsalgia@coh.org.
2
Eli Lilly and Company, Indianapolis, IN, United States.
3
Florida Cancer Specialists, St. Petersburg, FL, United States.
4
Florida Cancer Specialists, Fort Myers, FL, United States.
5
PharPoint Research Inc., Durham, NC, United States.
6
Lung Cancer Research Program, Sarah Cannon Research Institute, LLC, Nashville, TN, United States.

Abstract

OBJECTIVES:

This multicenter, open-label, randomized phase II study evaluated the efficacy and safety of LY2510924 (LY) added to first-line standard of care (SOC) chemotherapy for extensive-disease small cell lung cancer (ED-SCLC) and explored the predictive value of C-X-C motif receptor 4 (CXCR4) tumor response.

MATERIALS AND METHODS:

Patients with treatment-naïve ED-SCLC were randomized (1:1) to receive up to six 21-day cycles of carboplatin/etoposide alone (SOC) or in combination with 20mg LY2510924 administered subcutaneously on days 1-7 of each cycle (LY+SOC). The primary efficacy endpoint was progression-free survival (PFS). Secondary endpoints were overall survival (OS), overall response rate (ORR), and safety. Response relative to CXCR4 expression on baseline tumor was an exploratory endpoint.

RESULTS:

Of 94 patients randomized, 90 received treatment (LY+SOC, n=47; SOC, n=43). Median PFS (95% confidence interval [CI]) was 5.88 (4.83, 6.24) months for LY+SOC versus 5.85 (4.63, 5.51) months for SOC (hazard ratio [95% CI], 1.01 [0.62, 1.63]; p=0.9806). Median OS (95% CI) was 9.72 (6.64, 11.70) months for LY+SOC versus 11.14 (8.25, 13.44) months for SOC. ORR was 74.5% for LY+SOC versus 81% for SOC. Safety results between arms were similar, although the following adverse events were more frequent on the LY+SOC arm: anemia (61.7% vs 46.5%), neutropenia (61.7% vs 53.5%), leukopenia (27.7% vs 9.3%), vomiting (27.7% vs 16.3%), and pneumonia (10.6% vs 2.3%). In patients whose baseline CXCR4 expression was above the optimal cutoff (H-score 210), the hazard ratio (95% CI) was 1.27 (0.51, 3.15).

CONCLUSION:

LY2510924 did not improve efficacy but had an acceptable toxicity profile when added to SOC for ED-SCLC.

TRIAL REGISTRATION:

ClinicalTrials.gov NCT01439568.

KEYWORDS:

CXCR4; Extensive-disease small cell lung cancer; LY2510924; Phase II trial

PMID:
28236984
DOI:
10.1016/j.lungcan.2016.12.020
[Indexed for MEDLINE]

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