Byrd et al. Page 3918

Ibrutinib, an inhibitor of Bruton's tyrosine kinase (BTK), has shown great efficacy in chronic lymphocytic leukemia (CLL). To assess the long-term impact of ibrutinib treatment, Byrd and colleagues performed a long-term extension study, following patients with CLL and small lymphocytic leukemia (SLL) treated with ibrutinib for up to 8 years. Sustained efficacy of ibrutinib was observed, including for patients with high-risk genomic profiles. Ibrutinib was well-tolerated during follow-up as well. These data provide strong evidence for use of ibrutinib in patients with CLL/SLL, even those with unfavorable disease characteristics.

Fader et al. Page 3928

Her2/Neu, the target of the monoclonal antibody trastuzumab, is overexpressed in approximately 30% of uterine-serous-carcinoma (USC), a highly aggressive variant of endometrial cancer. Fader and colleagues report the final results of a randomized multicenter phase II trial of trastuzumab (T) in combination with carboplatin/paclitaxel (C/p. compared with carboplatin/paclitaxel (C/P) alone in USC patients overexpressing Her2/Neu. T/C/P-treated patients achieved a significantly longer progression-free-survival (PFS) and overall-survival (OS) when compared to C/P patients. The benefit was most notable in USC patients with stage III–IV disease. These findings support T/C/P as a new standard for USC patients overexpressing HER2/Neu.

Shi et al. Page 3979

Recent work has demonstrated that glypican-3 (GPC3) is a potential immunotherapeutic target in hepatocellular carcinoma (HCC). To explore the novel therapeutic strategy for HCC, Shi and colleagues conducted two phase I clinical trials using CAR-GPC3 T-cell therapy in patients with advanced GPC3-positive HCC. The results demonstrated that CAR-GPC3 T-cell therapy was feasible and well tolerated in patients with advanced HCC, and early signals of antitumor activity were observed. Thus, CAR-GPC3 T-cell therapy shows promise for treating HCC and should undergo further clinical examination.

Cooper et al. Page 4072

The search for new oncogenic drivers in non-small cell lung cancer (NSCLC) remains an ongoing challenge. Cooper and colleagues studied a patient with advanced NSCLC with a sustained response to sunitinib. Pursuing multiplatform genomic analysis of the responder's tumor tissue, RNA sequencing identified a novel gene fusion, TMEM87A-RASGRF1. Oncogenicity of this fusion and its ability to activate MAPK pathway were validated in vitro using CRISPR-Cas9. As the diversity of oncogenic drivers in lung cancer grows, further genomic analysis of patients considered to be outliers, including with RNA sequencing, represents an important mechanism to identify similar unanticipated oncogenic events.