Immune checkpoint inhibitors (ICI) cemiplimab and pembrolizumab have revolutionized the treatment of advanced cutaneous squamous cell carcinoma (cSCC). We aimed to evaluate the effectiveness and safety of ICI in a real-world cSCC population, including patients with conditions that would exclude clinical trial participation. In this single-center, retrospective cohort study, we included all non-trial patients with advanced cSCC treated with ICI between 2017 and 2022. We evaluated investigator-assessed best overall response (BOR) and immune-related adverse events (irAEs). We correlated survival outcomes with age, performance status, immune status and irAEs. Of the 36 patients identified, the best overall response (BOR) to ICI was a partial response (PR) in 41.7%, a complete response (CR) in 27.8%, and stable disease in (SD) 13.9%. The progression-free survival (PFS) rate for 1 year was 58.1%; the median PFS was 21.3 months (95% CI 6.4–NE). The 1-year overall survival (OS) was 76.7%, and the median OS was 38.6 months (95% CI 25.4–NE). Immune-compromised patients, ECOG performance 2–3, and age ≥ 75 years were not significantly associated with PFS or OS. IrAE grades 3–4 were seen in 13.9% of patients. In our Canadian experience with real-world patients, ICI was an effective and safe treatment for advanced cSCC patients. Patients achieved great benefits with ICI regardless of age, immune status or ECOG performance status. We acknowledge the small sample size and retrospective methodology as the main limitations of our study.

The incidence of melanoma among young adults has risen, yet mortality has declined annually since the introduction of immune checkpoint inhibitors (ICI). The utilization of peri-operative ICI has significantly altered the treatment landscape in melanoma, with PD-1 inhibitors showing promising efficacy in improving relapse-free survival rates in high-risk stage II-III disease. With the increasing use of ICI, secondary concerns have emerged regarding the impact of cancer drugs on fertility and reproductive health among women of childbearing potential, especially in early-stage cancer settings. The exclusion of pregnant women from trials contributes to limited human data and clinical uncertainties, such as maternal and fetal toxicities related to ICI exposure during pregnancy, as well as the value of fertility preservation before ICI therapy. Uncertainty persists regarding pregnancy post-adjuvant immunotherapy, given the potential detrimental effects of hormonal and immunological changes during pregnancy on melanoma relapse. There is additional uncertainty about whether pregnancy-associated melanoma (PAM) represents a distinct disease entity that warrants tailored management compared to non-pregnant cases. Our review aims to give an overview of oncofertility practices among female melanoma patients after immunotherapy. We also focus on the literature gap in the published evidence and synthesize summaries regarding ICI toxicities on reproductive health and fetal development, pregnancy planning, and recurrence risks after melanoma treatment.

: Immune checkpoint inhibitors (ICI) cemiplimab and pembrolizumab have revolutionized the treatment of advanced cutaneous squamous cell carcinoma (cSCC). We aimed to evaluate the effectiveness and safety of ICI in a real-world cSCC population, including patients with conditions which would exclude clinical trial participation. In this single-center, retrospective cohort study, we included all non-trial patients with advanced cSCC treated with ICI between 2017 and 2022. We evaluated investigator-assessed best overall response (BOR) and immune-related adverse events (irAEs). We correlated survival outcomes with age, performance status, immune status and irAEs. For the 36 patients identified, best overall response (BOR) to ICI was partial response (PR) in 41.7%, complete response (CR) in 27.8%, and stable disease in (SD) 13.9% of patients. The PFS rate at 1 year was 63%; median PFS was not reached (NR). The median OS was 38.6 months (95% CI 25.4-NR). Immune compromised patients, ECOG performance 2-3, and age ≥75 years were not significantly associated with PFS or OS. IrAE grade 3-4 were seen in 13.9% of patients. In our Canadian experience with real-world patients, ICI was an effective and safe treatment for advanced cSCC patients. Patients achieved great benefit with ICI regardless of age, immune status or ECOG performance status.

Background/Objectives: Cancer of unknown primary (CUP) remains a significant challenge in the field of oncology. Despite advances elsewhere in the field, there have been few advances in the treatment of CUP and correspondingly no improvements in patient survival. Recent studies utilizing molecular profiling, including next-generation sequencing (NGS), and molecularly targeted treatment of CUP have shown some promising initial results, but have yet to be integrated into the standard of care in most jurisdictions. This study aimed to assess the use of molecular characterization and targeted treatment of patients with CUP treated at Princess Margaret Cancer Centre (PMCC). Methods: This study is a retrospective audit of patients with CUP treated between January 2019 and April 2024 to build understanding of the accessibility and use of these molecular tools. Results: We found that 82% of the 28 patients identified received NGS analysis, though all received the results late in their disease course and all accessed molecular profiling via either clinical trials, a charitable access programme, or a privately source outside of the hospital network. Only 13% of the patients who received molecular analysis received any modification of care as a result of this profiling, and only as third line of treatment. Conclusions: Our data highlights a lag between current understanding and current practice, and identifies a possible area for improvement of patient care by standardizing the use of molecular analysis in the early workup and targeted therapy in the treatment of CUP.