Analysis of a large cohort of patient tumor samples from four international adjuvant chemotherapy trials confirms the prognostic value of the latest, soon-to-be-published, World Health Organization lung adenocarcinoma classifications, investigators reported online April 27 in the Journal of Clinical Oncology.

More than half of all patients with early-stage non–small cell lung cancer will have recurrence after primary surgery and “identifying prognostic factors beyond stage is crucial to select patients who need adjuvant therapies … The results of our study represent the first markers, to our knowledge, from the LACE-Bio [the Lung Adjuvant Cisplatin Evaluation Biomarker] project that suggest a significant predictive value for survival benefit from ACT [adjuvant chemotherapy] in patients with early-stage lung adenocarcinoma,” Dr. Ming-Sound Tsao with the Princess Margaret Cancer Centre, University of Toronto, and his colleagues wrote (J. Clin. Oncol. 2015 Apr. 27 [doi:10.1200/JCO.2014.58.8335]).

A new lung adenocarcinoma classification system based on the predominant histological pattern observed in resected tumors, including lepidic (LEP), papillary (PAP), acinar (ACN), micropapillary (MIP), and predominantly solid (SOL) subgroups, forms the basis for the fourth edition of the WHO classification to be published in 2015. The LACE-Bio collaborative group evaluated biomarkers using data from a large cohort of patients participating in four ACT trials: the IALT (International Adjuvant Lung Cancer Trial), ANITA (Adjuvant Navelbine International Trialist Association), JBR-10, and CALGB (Cancer and Leukemia Group B; now Alliance for Clinical Trials in Oncology).

The current study evaluated the prognostic value of the classification regarding survival from adjuvant chemotherapy using hematoxylin and eosin (HE)-stained slides from a subset of these patients. Because of the low numbers of representative samples in some groups, the five subtypes were collapsed into three groups: LEP, ACN/PAP, and MIP/SOL.

Patients with invasive lung adenocarcinoma with MIP and SOL patterns had poorer disease-free survival (DFS) and specific disease-free survival (SDFS) compared with the ACN/PAP subtypes. Furthermore, in early-stage adenocarcinoma, MIP/SOL-predominant histology predicted benefit from ACT in DFS and SDFS.

Multivariate analysis showed a marginally significant chemotherapy benefit in OS for MIP/SOL (hazard ratio, 0.71; 95% confidence interval, 0.51-0.99; P = .04) but not for ACN/PAP. There was a significant ACT benefit within the MIP/SOL group for DFS and SDFS (P < .001 for both), but not within the ACN/PAP group.

At a median follow-up of 5.6 years, among 575 patients, there were 269 (47%) events for OS, 320 (56%) for DFS, and 292 (51%) for SDFS. The primary endpoint was OS, and secondary endpoints were DFS, defined as time from random assignment to first event (recurrence or death) and specific DFS defined as time to first cancer-related event. The prognostic impact of adenocarcinoma subtype on ACT benefit was determined by comparison with 293 patients in the observation arm who did not receive ACT.

Several previous studies demonstrated that patients with lung adenocarcinoma with predominantly MIP and SOL patterns had the worst outcomes. The association of the MIP growth pattern and poor outcomes in breast cancer is well known. The SOL pattern describes poorly differentiated carcinomas, and higher rates of this subtype have been observed in studies that included patients with higher stage disease.

“We have shown the first evidence to our knowledge that MIP/SOL–predominant histology is a promising predictive marker for benefit from ACT in DFS and SDFS in patients with early-stage lung adenocarcinoma; however, more analyses are needed to confirm these findings,” they wrote.