Background/Objectives: The clinical value of KRAS mutations in lung adenocarcinoma, alone or in combination with other mutations, has been assessed especially in advanced stages. This study evaluates how KRAS and the presence of co-mutations could affect survival in early-stage lung. Methods: We analyzed a real-world cohort including all staged NSCLC patients diagnosed and treated from 2018 to 2022 at our Institute with availability of NGS molecular data. Statistical analyses were made using log-rank test, the two-tailed Fisher’s exact test and Kaplan-Meier survival curves. Results: KRAS mutations were observed in 179/464 cases (38.6%). The majority of KRAS co-mutations were in TP53 (74%) and STK11 (14.3%) genes. KRAS+TP53 co-mutations were more frequent compared to KRAS-only tumors in stage IV NSCLC (p = 0.01). In early stage and locally advanced cases (stage I-III), better prognosis was associated to KRAS-only mutated NSCLC and to KRAS+STK11 mutated cases compared to KRAS+TP53 (p = 0.008). In particular, patients carrying KRAS+TP53 in stage I and II displayed a shorter survival, similar to patients diagnosed at stage III. Conclusions: Routine NGS provides important information for potential actionable mutations but also for the prognostic and predictive role of the presence of co-occurring mutations. In particular, the presence of KRAS+TP53 in stage I and II NSCLC may be considered an unfavorable prognostic marker possibly leading to adapt the perioperative chemo-immunotherapy.

Background: Adherence to oral anticancer therapies among breast cancer patients is an often-overlooked issue. A lack of patient compliance can be caused by several factors, and may hinder the efficacy of prescribed medication, leading to a shorter than expected survival. In this context, few data about adherence to CDK4/6 inhibitors in real-world practice are available. We report here the results of a retrospective analysis of adherence to abemaciclib plus endocrine therapy in a cohort of women with hormone receptor-positive (HR+), epidermal growth factor 2 negative (HER2−) breast cancer. Methods: Abemaciclib adherence was computed as the ratio between the total number of cycles/months that medication was supplied and the months between the first and the last prescription. The proportion of Days Covered (PDC) ranged from 0 to 1. A score of 0.8 (i.e., 80% adherence rate) was the cutoff used to classify the patients as adherent (0.8 ≤ PDC ≤ 1) or non-adherent (0 ≤ PDC < 0.8). The received dose intensity was also calculated. Results: The abemaciclib pharmacy claims of 100 women with HR+/HER2− breast cancer were retrieved. Most patients (91%) were treated in the advanced setting. Abemaciclib was more frequently taken with an aromatase inhibitor (63%) than with fulvestrant (27%). In this population, the adherence rate was high (92.25% + 1.939 SD). The proportion of non-adherent patients taking abemaciclib with PDC <0.8 was 12%. There was a significative correlation between the occurrence of side effects and the use of <5 drugs for non-oncological illnesses, probably reflecting concomitant non-oncological diseases. Conclusions: Adherence to abemaciclib-based therapy is high in a real-life setting, pending the adequate and proactive management of patients. The careful evaluation of patients and detailed information about expected adverse events are essential to ensure adherence to this antineoplastic agent.

Background. In recent years, the role of prostate-specific membrane antigen (PSMA) in the imaging and treatment of prostate cancer (PCa) has been extensively investigated. However, despite its name, PSMA is not exclusively specific to PCa. It has been found to be expressed in the neo-vasculature of various solid tumors, including breast cancer (BC), in which it is associated with tumor angiogenesis. Methods. This review aims to assess the potential of PSMA-based radiopharmaceuticals for BC diagnosis and treatment. It explores the current landscape by analyzing preclinical and clinical studies, as well as ongoing clinical trials, to provide insights into the PSMA-targeted approaches in BC management. Results. Early studies suggest PSMA-based imaging could improve BC lesion detection, especially in TNBC. The available data remains too preliminary to conclusively assess whether PSMA-based imaging or therapy will offer a significant advantage in BC. However, some preclinical findings suggest that this approach may hold promise as a novel strategy for managing this widespread malignancy. Conclusions. PSMA-based strategies show potential for BC diagnosis and treatment, but further research is needed. Ongoing and future clinical trials are expected to provide deeper insights into the potential utility of this approach.

Background/Objectives: The clinical value of KRAS mutations in lung AC, alone or in combination with other mutations, has been assessed especially in advanced stages. This study evaluates how KRAS and the presence of co-mutations could affect survival in early-stage lung. Methods: We analyzed a real-world cohort including all staged NSCLC patients diagnosed and treated from 2018 to 2022 at our Institute with availability of NGS molecular data. Statistical analyses were made using log-rank test, the two-tailed Fisher's exact test and Kaplan-Meier survival curves. Results: KRAS mutations were ob-served in 179/464 cases (38.6%). The majority of KRAS co-mutations were in TP53 (74%) and STK11 (14.3%) genes. KRAS+TP53 co-mutations were more frequent compared to KRAS-only tumors in stage IV NSCLC (p=0.01). In early stage and locally advanced cases (stage I-III), better prognosis was asso-ciated to KRAS-only mutated NSCLC and to KRAS+STK11 mutated cases compared to KRAS+TP53 (p=0.008). In particular, patients carrying KRAS+TP53 in stage I and II displayed a shorter survival, similar to patients diagnosed at stage III. Conclusions: Routine NGS provides important information for potential actionable mutations but also for the prognostic and predictive role of the presence of co-occurring mutations. In particular, the presence of KRAS+TP53 in stage I and II NSCLC may be considered an unfavorable prognostic marker possibly leading to adapt the perioperative chemo-immunotherapy.

Background: Adherence to oral anticancer therapies among breast cancer patients is an often-overlooked issue. Lack of patients’ compliance can be caused by several factors, and may hinder the efficacy of prescribed medication, determining shorter than expected survival. In this context, few data are available about adherence to CDK4/6 inhibitors in the real-world practice. We report here the results of a retrospective analysis of adherence to abemaciclib plus endocrine therapy in cohort of women with hormone receptor-positive (HR+), epidermal growth factor 2 negative (HER2-) breast cancer. Methods: Abemaciclib adherence was computed as the ratio between the total number of cycles/months of supply for medication and months between the first and the last prescription. The proportion of Days Covered (PDC) may range from 0 to 1. A score of 0.8 (i.e. 80% adherence rate) was the cutoff to classify the patients as adherent (0.8 ≤ PDC ≤1) or non-adherent (0 ≤ PDC <0.8). Received dose intensity was also calculated. Results: Abemaciclib pharmacy claims of 100 women with HR+/HER2- breast cancer were retrieved. Most patients (91%) were treated in the advanced setting. Abemaciclib were more frequently taken with an aromatase inhibitor (63%), than with fulvestrant (27%). In this population, adherence rate was high (92.25% + 1.939 SD). The proportion of non-adherent patients taking abemaciclib with PDC <0.8 was 12%. There was a significative correlation between the occurrence of side effects and polypharmacy, probably reflecting concomitant non-oncological diseases. Conclusions: Adherence to abemaciclib-based therapy is high in a real-life setting, pending adequate and proactive management of patients. Careful patients’ evaluation and detailed information about expected adverse events are essential to ensure adherence to this antineoplastic agent.

Background/Objectives: Several genetic alterations have been identified as drivers of uncontrolled cell growth in lung cancer, with KRAS mutations representing the most prevalent driver oncogene. Despite advances in targeted treatment, the 5-year survival rate of patients with advanced/metastatic NSCLC is still less than 20%. This study aims to assess the clinical relevance of KRAS mutations in the context of PD-L1 expression, focusing on patients with PD-L1 Tumor Proportion Score (TPS) ≥ 50% and treated with first-line immune checkpoint inhibitors (ICIs). Methods: We conducted a retrospective analysis of a real-world cohort comprising all staged NSCLC patients diagnosed and treated between 2018 and 2022 at our Institution with the available Next Generation Sequencing and PD-L1 immunohistochemistry results. Statistical analyses were made using the log-rank test, the two-tailed Fisher’s exact test, and Kaplan–Meier survival curves. Results: Among 520 NSCLC patients, 288 were adenocarcinoma (AC). Of these, 110/288 (38.2%) were KRAS mutants, and 83/278 (29.8%) presented a PD-L1 TPS ≥ 50%. In this subgroup, KRAS mutants demonstrated longer median overall survival (mOS) and progression-free survival (PFS) compared to the KRAS wild-type (28.7 vs. 10.7 months, p = 0.010; 6.4 vs. 3.5 months, p = 0.005, respectively). While OS did not differ among KRAS mutation subtypes, PFS was significantly shorter in patients with p.G12D (3.5 months, p = 0.03). Conclusion: This study is the first to investigate the interplay between KRAS mutations and PD-L1 expression in a real-world stage IV lung AC cohort treated with ICIs. Our findings indicate that the p.G12D mutation is associated with an extremely severe disease upon ICI monotherapy. These preliminary results need further validation in larger, prospective cohorts.