Local consolidative therapy prolongs PFS in patients with metastatic NSCLC

CHICAGO — Local consolidative therapy, with or without systemic therapy, improved PFS in patients with oligometastatic non–small cell lung cancer previously treated with induction systemic therapy, according to study results presented at the ASCO Annual Meeting.

“These data are provocative, as it is the first randomized prospective study to demonstrate a benefit for aggressive local therapy,” Daniel Gomez, MD, assistant professor in the department of radiation oncology at The University of Texas MD Anderson Cancer Center, told HemOnc Today. “Several retrospective studies have suggested a benefit, but there are often significant limitations in these analyses.”

Gomez and colleagues identified patients with histologically confirmed stage IV NSCLC and three or fewer metastases who did not experience progression after induction systemic therapy.

Induction systemic therapy consisted of four or more cycles of platinum doublet therapy, or 3 or more months of treatment with erlotinib (Tarceva; Genentech, Astellas Oncology) or crizotinib (Xalkori, Pfizer) for patients with EGFR mutations or ALK fusions.

The researchers randomly assigned patients to local consolidative therapy — consisting of chemoradiation or surgical resection of all sites, with or without systemic therapy — or systemic therapy alone. Systemic therapy was at physicians’ discretion and based on predefined standard-of-care regimens.

PFS served as the primary endpoint.

The researchers planned to enroll 94 patients; however, the study closed early due to significant efficacy in the investigational arm.

The analysis included data from 74 patients. Prior to closure, the study had enrolled 49 patients (local consolidative therapy, n = 25; systemic therapy; n = 24). The remaining 25 patients were enrolled after randomization ceased.

Median follow-up was 18.7 months.

Patients assigned local consolidative therapy had a median PFS of 11.9 months (95% CI, 5.2-not reached), compared with 3.9 months (95% CI, 2.2-6.6) among those assigned systemic therapy alone (HR = 0.36; P = .013).

Three patients in the systemic therapy arm crossed over to the investigational arm prior to progression, all due to toxicity. An additional 11 patients crossed over after experiencing progression.

Thirty patients experienced progression. A higher proportion of locoregional failure occurred in the systemic therapy only arm (17% vs. 4%), whereas the local consolidative therapy arm had higher proportions of metastatic failures (40% vs. 25%).

However, the systemic therapy arm had a higher percentage of combined locoregional and metastatic failures (29% vs. 8%).

A total of 14 deaths had occurred at the time of reporting (investigational arm, n = 6; systemic therapy arm, n = 8). Median OS has not been reached. The researchers continue to monitor patients for this endpoint.

The researchers performed an exploratory analysis in which patients with EGFR or ALK alterations were removed. The PFS benefit seen with local consolidative therapy persisted (HR = 0.41; 95% CI, 0.19-0.9).

“We hope to use these results to initiate a larger study that further addresses the question, and will perhaps also utilize novel systemic agents,” Gomez said. – by Cameron Kelsall

Reference:

Gomez DR, et al. Abstract 9004. Presented at: ASCO Annual Meeting; June 3-7, 2016; Chicago.

Disclosure: Gomez reports research funding from Merck and travel expenses from ProCure. Please see the abstract for a list of all other researchers’ relevant financial disclosures.