This comprehensive review highlights the history of discovering RAS and the decades of studies targeting KRAS-driven lung cancer, to the present applications. Although KRAS inhibitors have 36%–45% objective response rates with a median duration of response of 10 months, many tumors do not respond, and a variety of mechanisms of resistance have been observed, including new KRAS alterations, activation of alternate RTK pathway proteins, bypass pathways, and transcriptional remodeling. The authors conclude with a discussion of ongoing clinical trials aimed at overcoming resistance to KRAS inhibitors.

In this trial of nivolumab + chemotherapy vs. chemotherapy alone, nivolumab prolonged EFS by nearly 11 months and improved the pathologic complete response rate more than tenfold. There was also a trend toward improved OS with nivolumab. The study also reported an EFS improvement with nivolumab in both squamous and non-squamous NSCLC. Grade 3-4 treatment-related adverse events occurred in 34% of patients in the nivolumab arm and 37% of those in the chemotherapy-alone arm.

Nivolumab plus ipilimumab added to standard of care chemotherapy did not improve outcomes as 1st line therapy for unresectable or metastatic bladder cancers with PD-L1 expression > 1%.

CAR T-cell therapy has changed the treatment paradigm for relapsed/refractory aggressive B-cell NHL. The approach has seen strong response rates and durable remission in those whose disease has progressed despite multiple prior treatments. This review outlines current indications for CAR T-cell therapy, major toxicities, novel CARs under investigation, CARs for various hematologic malignancies, and future directions.

In this 15-minute CME activity, two experts provide a rundown of multiple disease factors to consider, evolving clinical trial data, and the various therapeutic options available in the second and subsequent lines of therapy for patients with locally advanced or metastatic urothelial carcinoma.

In an interim look at the SKYSCRAPER-01 study, investigators found tiragolumab plus atezolizumab didn’t meaningfully slow tumor progression compared to atezolizumab alone in patients with advanced, newly diagnosed non-small cell lung cancer (NSCLC). Tiragolumab has now fallen short in two phase 3 lung cancer trials, having already missed its study objectives in advanced SCLC earlier this year.