No abstract

Highlights KRAS mutation is a major driver in mesonephric and mesonephric-like carcinomas of cervical, endometrial or ovarian origin. ARID1A and PIK3CA mutations were also identified in endometrial and ovarian mesonephric-like carcinomas. Peripheral blood ctDNA liquid biopsy may detect mutations in recurrent and/or metastatic mesonephric carcinomas.

Key Points Question What is the comparative effectiveness of single-agent immune checkpoint inhibitors (ICIs) vs taxane chemotherapy in populations of patients with metastatic castration-resistant prostate cancer (mCRPC) defined by levels of tumor mutational burden (TMB)? Findings In this comparative effectiveness study of 741 patients with mCRPC, patients with TMB of 10 mutations per megabase (mt/Mb) or greater had significantly longer time to next treatment and overall survival with ICIs vs taxanes. Meaning These findings suggest that in scenarios where taxane use is considered, ICIs are a viable alternate treatment option for patients with mCRPC and TMB of 10 mt/Mb or greater.

Based on the approvals of crizotinib and entrectinib by the Food and Drug Administration for the treatment of ROS1 positive nonsmall cell lung cancer (NSCLC), we sought to examine the mutational profile of a variety of solid tumors (excluding sarcomas) with ROS1 fusions that underwent comprehensive genomic profiling. A review of our database was performed to extract all nonsarcoma patients with ROS1 fusions that were discovered by the hybrid capture‐based DNA only sequencing assays. We examined the coalterations representing potentially targetable biomarkers, resistance alterations and other alterations in these cases. In addition, we examined the histologic characteristics and protein expression with immunohistochemistry (IHC). From a series of clinically advanced nonsarcoma solid tumors, 356 unique cases with ROS1 fusions included 275 (77.2%) NSCLC and 81 (22.8%) non‐NSCLC. Ten novel ROS1 fusions were discovered. Importantly, the NSCLC ROS1 fusionpos tumors had a higher PD‐L1 IHC expression positivity when compared to the NSCLC ROS1 fusionneg population (P = .012, Chi‐squared). The frequency of known and likely anti‐ROS1 targeted therapy resistance genomic alterations in NSCLC was 7.3% (20/275) and in non‐NSCLC was 4.9% (4/81). Overall, the coalteration profile of ROS1 fusionpos NSCLC and non‐NSCLC was similar with only three genes altered significantly more frequently in non‐NSCLC vs NSCLC: TERT, PTEN, APC. In our study, we characterized a large cohort of ROS1 fusionpos NSCLC and non‐NSCLC solid tumors and discovered 10 novel ROS1 fusions.

Assessment of programmed cell death-ligand 1 (PD-L1) expression by immunohistochemistry (IHC) is the definite diagnostic test to guide treatment for patients with advanced-stage non-small cell lung cancer. Intratumoral heterogeneity and discrepancy of PD-L1 expression between primary and metastatic lesions may increase the risk of tumor misclassification. We performed a retrospective study of the Foundation Medicine, Inc clinical database on lung cancer cases that were evaluated for PD-L1 expression by IHC in the context of routine care. All cases were assessed with the Food and Drug Administration-approved 22C3 pharmDx assay and scoring system. 15,028 lung cancer cases, including 8285 primary tumors and 6743 unmatched metastatic lesions were analyzed. Metastatic lesions (mets) were more frequently high positive (tumor proportion score (TPS) ≥50%) for PD-L1 expression than primary lesions (33.8% vs 28.4%; OR, 1.28; 95% CI, 1.19 to 1.37; p<0.001). Higher levels in mets than primaries were seen in samples from lymph nodes, pleural fluid, soft tissue and adrenal gland but not in those from liver, brain and bone. Metastatic lesions of patients with non-squamous histology were more likely to have TPS ≥50% in comparison with primary (OR, 1.37; 95% CI, 1.27 to 1.49; p<0.001), but this was not the case for patients with squamous histology (OR, 0.89; 95% CI, 0.74 to 1.06; p=0.197). PD-L1 expression varies with respect to histologic subtype, sampling site and gender, but is generally higher in metastatic sites. This observation may affect future patient management and trial design.