Mutations in STK11 (STK11^Mut) and, frequently co-occurring, KEAP1 mutations (KEAP1^Mut) are associated with poor survival in metastatic Non-small Cell Lung Cancer (mNSCLC) patients treated with immunotherapy. However, there are limited data regarding the prognostic or predictive significance of these genomic alterations among Hispanics. This retrospective study analyzed a cohort of Hispanic patients (N = 103) diagnosed with mNSCLC from the US and seven Latin American countries (LATAM) treated with immune checkpoint inhibitors (ICI) alone or in combination as first-line (Cohort A). All cases were treated in routine care between January 2016 and December 2021. The main objectives were to determine the association of mutations in STK11 or KEAP1 in these patients' tumors with overall (OS) and progression-free survival (PFS), presence of KRAS mutations, tumor mutational burden (TMB), and other relevant clinical variables. To compare outcomes with a STK11^Wt/KEAP1^Wt population, historical data from a cohort of Hispanic patients (N = 101) treated with first-line ICI was used, matching both groups by country of origin, gender, and Programed Death-ligand 1 (PD-L1) expression level (Cohort B). Most tumors had mutations only in STK11 or KEAP1 (45.6%) without KRAS co-mutation or any other genomic alteration. Besides, 35%, 8.7%, 6.8%, and 3.9% were KRAS^Mut + STK11^Mut, KRAS^Mut + STK11^Mut + KEAP1^Mut, STK11^Mut + KEAP1^Mut, and KRAS^Mut + KEAP1^Mut, respectively. Based on KRAS status, STK11 alterations were associated with significantly lower PD-L1 expression among those with KRAS^Wt (p = 0.023), whereas KEAP1 mutations were predominantly associated with lower PD-L1 expression among KRAS^Mut cases (p = 0.047). Tumors with KRAS^Mut + KEAP1^Mut had significantly higher median TMB when compared to other tumors (p = 0.040). For Cohort A, median PFS was 4.9 months (95%CI 4.3-5.4), slightly longer in those with KEAP1^mut 6.1 months versus STK11^Mut 4.7 months (p = 0.38). In the same cohort, PD-L1 expression and TMB did not influence PFS. OS was significantly longer among patients with tumors with PD-L1 ≥ 50% (30.9 months), and different from those with PD-L1 1-49% (22.0 months), and PD-L1 < 1% (12.0 months) (p = 0.0001). When we compared the cohorts A and B, OS was significantly shorter for patients carrying STK1 [STK11^Mut 14.2 months versus STK11^Wt 27.0 months (p = 0.0001)] or KEAP1 [KEAP1^Mut 12.0 months versus KEAP1^Wt 24.4 months (p = 0.005)] mutations. PD-L1 expression significantly affected OS independently of the presence of mutations in STK11, KEAP1, or KRAS. TMB-H favored better OS. This is the first large Hispanic cohort to study the impact of STK11 and KEAP1 mutations in NSCLC patient treated with ICI. Our data suggest that mutations in the above-mentioned genes are associated with PD-L1 expression levels and poor OS.

Uveal melanoma is the most prevalent and aggressive intraocular malignancy affecting adults. Compared with cutaneous melanoma, uveal melanoma has distinct pathogenesis and molecular characteristics. Not surprisingly, it derives limited benefits from checkpoint inhibitors. Until recently, no systemic therapy had impacted survival outcomes for this patient population. Tebentafusp, a T-cell receptor-based molecule, is the first US Food and Drug Administration/European Medicines Agency-approved systemic therapy to improve the survival outcomes for uveal melanoma patients expressing HLA-A∗02:01. Only 45%-50% of this patient population will express the HLA-A∗02:01, however, and therefore are eligible to receive this novel treatment. Moreover, global access to tebentafusp is limited, and there are no guidelines to aid clinicians in decision-making regarding treatment. In this review, we outline our experience as Canada's largest tertiary referral centre in managing metastatic uveal melanoma patients and provide a comprehensive overview of the currently available treatment options, challenging scenarios, and ongoing clinical trials for patients with metastatic uveal melanoma.

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.