Background KRAS is the most frequently mutated gene in non-small cell lung cancer (NSCLC), however conflicting data are available on its role as a biomarker. Objective The aim of our work was to investigate the impact of KRAS mutations on response and survival outcomes in advanced non-squamous NSCLC patients treated with immune checkpoint inhibitors alone or in combination with chemotherapy. Patients and Methods We retrospectively identified 119 patients, most of whom (58%) were KRAS wild type. For each patient we evaluated overall survival (OS), progression-free survival (PFS), and disease control rate (DCR). An exploratory analysis was performed among KRAS mutated patients to investigate the impact of specific KRAS mutations on response and survival outcomes. Results After a median follow-up of 10.3 months, the median OS was 14.9 months (95% confidence interval [CI] 7.6–22.7) in wild-type KRAS patients versus 14.7 months (95% CI 8.0–19.5) in mutated KRAS patients (p = 0.529). No differences were detected between the two groups in terms of PFS and DCR. Patients with a KRAS G12C mutation reported survival and response outcomes that were not statistically different from those of patients with other KRAS mutations. Conclusion Our data confirmed that KRAS mutational status is not associated with survival and response outcomes in advanced non-squamous NSCLC patients treated with immunotherapy alone or combined with chemotherapy.

Introduction: In recent years, several inflammation-related factors and nutritional parameters have been evaluated to develop prognostic scores as potential biomarkers in non-small-cell lung cancer (NSCLC) patients receiving immune checkpoint inhibitors (ICIs). The aim of this study was to retrospectively investigate the prognostic role of the advanced lung cancer inflammation (ALI) index, lung immune prognostic index (LIPI), prognostic nutritional index (PNI) and systemic inflammation score (SIS) in metastatic NSCLC patients receiving ICI alone or in combination with chemotherapy. Methods and patients: We retrospectively included 191 patients with advanced NSCLC who received first-line ICI with or without chemotherapy from 2017 to 2024. The association between pretreatment ALI, LIPI, PNI, and SIS and overall survival (OS) was evaluated using the Kaplan–Meier method and Cox regression models. Results: After a median follow-up of 27.7 months, significantly longer OS was associated with an ALI score > 18 vs. ≤18 (18.0 vs. 7.3 months; p = 0.00111), LIPI score 0 vs. 1 and 2 [18.9 vs. 8.2 and 4.2 months; (p = 0.001)], PNI ≥ 45 vs. <45 (22.7 vs. 9.6 months; p = 0.002), and SIS score 0 vs. 1 and 2 (27.4 vs. 7.1 and 8.6 months, respectively; p < 0.001). The OS benefit was independent of treatment (ICI vs. ICI + chemotherapy). At multivariate analysis, pretreatment albumin was positively associated with OS, while ECOG PS 1 and liver metastases were negatively associated with OS. Conclusions: Inflammatory and nutritional biomarkers such as the ALI, LIPI, PNI, and SIS represent useful tools to prognosticate survival in metastatic lung cancer patients treated with ICI alone or in combination with chemotherapy as first-line.

Androgen deprivation therapy (ADT) is a cornerstone of treatment for prostate cancer and, in recent years, androgen receptor (AR)-targeted therapies (abiraterone and enzalutamide) have both been used for the treatment of castration-resistant prostate cancer (CRPC). In our study, we sought to investigate the association between ADT and immune disorders, considering a potential role of androgens in the immune modulation. We retrospectively evaluated CRPC patients treated with abiraterone/enzalutamide between July 2011 and December 2018. We assessed the risk of developing immune alterations and their impact on outcome. We included 844 CRPC patients receiving AR-directed therapies, of whom 36 (4.3%) had autoimmune diseases and 47 (5.6%) second tumors as comorbidities. Median age was 70 years [interquartile range (IQR) = 63–75)]. We showed higher significant incidence of autoimmune diseases during their hormone sensitive status (p = 0.021) and the presence of autoimmune comorbidities before starting treatment with abiraterone/enzalutamide was significantly associated with worse overall survival (OS) (10.1 vs. 13.7 months, HR = 1.59, 95% CI 1.03–2.27, p = 0.038). In a multivariate analysis, the presence of autoimmune disorders was an independent predictor of OS (HR = 1.65, 95% CI 1.05–2.60, p = 0.031). In conclusion, CRPC patients with autoimmune alterations before starting AR-directed therapies may have worse prognosis. Further prospective studies are warranted to assess the role of immune modulation in the management of prostate cancer patients.

The treatment of epidermal growth factor receptor (EGFR)-mutant non-small-cell lung cancer (NSCLC) patients was dramatically revolutionized by the introduction of EGFR tyrosine kinase inhibitors in clinical practice, both in advanced and locally advanced/early stages. The present work focuses on osimertinib use in locally advanced and early NSCLC stages. Phase 3 clinical trials have supported the use of osimertinib as the new standard of care, both in the adjuvant setting and in locally advanced disease. The ADAURA study reported an overall survival (OS) advantage for adjuvant osimertinib in completely resected stage II-IIIA EGFR-mutant tumors, while the LAURA study proved a statistically significant benefit in progression-free survival (PFS) and a delay of central nervous system metastasis development in EGFR-mutant patients treated with osimertinib maintenance after concurrent chemoradiotherapy for locally advanced disease. In the neoadjuvant setting, data on osimertinib’s efficacy are conflicting; therefore, the Neo-ADAURA study is evaluating the efficacy and safety of neoadjuvant osimertinib alone or in combination with chemotherapy in patients with stage II-IIIB NSCLC and common EGFR mutations. We discuss several issues that need to be clarified, such as the efficacy of the drug on uncommon mutations, the long-term impact on survival, and the management of resistance mechanisms. Moreover, we report the studies that are trying to identify potential biomarkers of response, such as the circulating tumor DNA (ctDNA), with the aim of selecting patients who will benefit most from osimertinib.