Combination treatment with Enfortumab vedotin (EV), an antibody drug conjugate targeting Nectin-4 with a monomethyl auristatin E (MMAE) payload, and pembrolizumab, a programmed death 1 (PD-1) inhibitor, has become the new standard of care for previously untreated locally advanced or metastatic urothelial carcinoma. In the recently published phase III study, EV-302, EV and pembrolizumab demonstrated improved outcomes compared to platinum-based chemotherapy, including objective response rate, progression free survival, and an unprecedented median overall survival of 33.8 months (versus 15.9 months; hazard ratio for death 0.51; 95% confidence interval 0.43-0.61; p < 0.00001). We reviewed the mechanism of action, clinical efficacy, exploratory biomarkers, and safety profile of EV and pembrolizumab as monotherapies and combination in urothelial cancer.

Anti‐PD‐1/PD‐L1 agents play a crucial part in the treatment of non‐small cell cancer (NSCLC) demonstrating improved overall response rate (ORR) and overall survival (OS). Recent studies evaluating combination treatment with anti‐PD‐1 and anti‐CTLA‐4 suggests improved outcome but also increased toxicity. Evidence is scarce regarding subsequent treatment with immune checkpoint inhibitors (ICPI) after progression on anti‐PD‐1/PD‐L1. A total of 15 patients were treated with a combination of anti‐PD1 agent and ipilimumab after confirmed progression of disease on anti‐PD1/PDL1 alone during 2017. Clinical data were retrieved retrospectively. Disease control rate (DCR) was defined as partial response (PR) or stable disease (SD). The overall DCR was 33.3% (n = 5); two patients with PR and three patients with SD, three of whom had prior documented disease control on anti‐PD1. The immune‐related adverse event (irAE) rate was 40% (n = 6); two patients had grade 3 AE and one patient died of pneumonitis. While the median time to progression was two months (range 0.5–16), four of the five patients with PR/SD experienced durable benefit for 8–16 months. This small retrospective cohort of heavily pretreated unselected patients suggests ipilimumab might reboost the immune response in patients with advanced NSCLC following progression of disease on anti‐PD1 therapy, while delaying exposure to the higher toxicity rates associated with upfront combination therapy. This strategy should be explored prospectively.

Background: Unfortunately, the majority of patients with colorectal cancer liver metastases (CRCLM) experience disease recurrence following hepatic surgery. The key challenge is therefore optimal patient selection, which currently relies on anatomical and clinical parameters. Exploring a potential molecular signature may be predictive for seeing a clinical benefit from CRCLM resection. Methods: Consecutive patients who underwent CRCLM resection at our medical center between 2006 and 2016 were divided into cohorts of “good prognosis” (GP) or “poor prognosis” (PP) based on the time interval between their resection and disease recurrence. Proteomic analysis was performed on the surgical specimen and correlation analysis was carried out with demographics and clinical outcomes. Results: Proteomic analysis revealed 99 differentially expressed proteins of which a third were associated with extracellular matrix (ECM) pathways as the matrix metalloproteinases (MMPs). Multivariate analysis yielded a statistically differential proteomic pattern between the cohort regardless of perioperative treatment. Conclusion: Our results indicate a different proteomic landscape in the cohort of patients who had a clinical benefit from CRCLM resection which appears to be correlated with ECM pathways. Further prospective studies are needed to define the role of ECM pathways in prognostics and patient selection for surgical procedures for CRCLM.

PURPOSE: Telemedicine is increasingly used in oncology research including informed consent discussions, but data evaluating the potential impact of telemedicine on the quality of informed consent are scarce. METHODS: Consecutive patients with genitourinary malignancies who underwent informed consent discussions for biomarker (next-generation sequencing) or therapeutic (phase I to III) clinical studies at the Memorial Sloan Kettering Cancer Center were asked to complete modified versions of the validated Quality of Informed Consent (QuIC) questionnaire evaluating objective (QuIC A) and subjective (QuIC B) understanding. The method used for the informed consent discussion (in-person or telemedicine) was at the physician's discretion. QuIC scores were compared between telemedicine and in-person cohorts using separate linear regression models for QuIC A and B scores and for biomarker and therapeutic protocols. Cochran's Q was calculated to evaluate heterogeneity between biomarker and therapeutic protocols. RESULTS: Of 320 eligible patients approached between January 2021 and July 2022, 239 patients completed the QuIC questionnaires after informed consent discussion for biomarker (n = 128) or therapeutic (n = 111) protocols, conducted via telemedicine (n = 49) or in person (n = 190). We did not find evidence that telemedicine and in-person consent differed between the biomarker and therapeutic studies for either QuIC A or B (heterogeneity P = .13 and P = .5, Respectively), and so the main analyses combined both study types. There were no differences between groups for QuIC A (adjusted difference, –1.3 [95% CI, –4.6 to 1.9]; P = .4), but QuIC B scores were significantly higher for telemedicine versus in-person consent for the therapeutic cohort (adjusted difference, –5.2 [95% CI, –10.3 to –0.01]; P = .049). CONCLUSION: Our results support the use of telemedicine for informed consent discussions in clinical cancer research studies of biomarkers and clinical trials.