Journal
JOURNAL OF THORACIC ONCOLOGY
Volume 10, Issue 1, Pages 110-115Publisher
ELSEVIER SCIENCE INC
DOI: 10.1097/JTO.0000000000000385
Keywords
Small-cell lung cancer; Platinum sensitive; Platinum refractory; Clinical trials; Treatment; Southwest Oncology Group
Categories
Funding
- NCI NIH HHS [N01 CA038926, UG1 CA233340, CA58882, N01 CA032102, U10 CA058882, U10 CA038926, U10 CA180819, U10 CA180888, K12 CA138464, N01 CA046441, U10 CA032102, U10 CA180846, U10 CA046441, P30 CA093373] Funding Source: Medline
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Background: Extensive-stage small-cell lung cancer (SCLC) patients who progress after platinum-based chemotherapy are traditionally categorized as platinum sensitive (progression >= 90 days from last platinum dose) or refractory (progression < 90 days), a practice arising from seminal observations of worse survival in refractory patients. Subsequent trials accounted for platinum sensitivity, resulting in higher sample sizes and increased resource use. Methods: To assess whether platinum-sensitivity status remains associated with outcomes, patient-level data from recent Southwest Oncology Group trials in second-and/or third-line extensive-stage SCLC were pooled. Hazard ratios (HRs) for progression-free survival (PFS) and overall survival (OS) accounting for platinum sensitivity were calculated using unadjusted and adjusted Cox Proportional Hazard models. Recursive partitioning was performed to define prognostic risk groups. Results: Of 329 patients, 151 were platinum sensitive and 178 refractory. HRs from unadjusted Cox PFS and OS models for refractory versus sensitive disease were 1.0 (95% confidence interval, 0.81-1.25; p = 0.98) and 1.24 (0.99-1.57; p = 0.06), respectively. Adjusted Cox models showed that only elevated serum lactate dehydrogenase (HR, 2.04; p < 0.001), males (HR, 1.36; p = 0.04), performance status of 1 (HR, 1.25; p = 0.02), and weight loss greater than or equal to 5% (1.53, p = 0.01) were independently associated with OS. Platinum-sensitivity status was not associated with PFS (HR, 1.11; p = 0.49) or OS (HR, 1.25; p = 0.14), except in a model that excluded 36 patients who received more than one prior chemotherapy regimen (HR, 1.34; p = 0.049). Prognostic groups with differential OS outcomes (high, intermediate, and poor risk) were identified. Conclusions: Platinum-sensitivity status may no longer be strongly associated with PFS or OS in at least one multivariate model. Validation of prognostic risk groups identified here is warranted. These data have critical implications in the design of future SCLC trials.
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