Eleonora Pagan

Background and Methods: Although OBS is a well‐established approach, evidence regarding its long‐term safety and outcomes in older women remains limited. We performed a retrospective analysis to identify patients ≥ 60 years who underwent OBS for breast cancer between 2001 and 2014. Patients were stratified into two age groups: elderly (60–74 years) and senior (≥ 75 years). Primary endpoints were disease‐free survival (DFS), overall survival (OS), and local recurrence rates. Secondary endpoints included post‐operative complication rates and distribution of OBS techniques according to age group. Results: 303 patients were identified, 287 (94.7%) elderly and 16 (5.3%) senior. Most patients (60.7%) had comorbidities. Fifteen patients had bilateral tumors, for a total of 318 operated breasts. Breast cancer was staged as Tis, T0, T1, T2, and T3 respectively in 15.1%, 1.3%, 48.1%, 33.3%, and 0.9% of breasts. Multicentricity and multifocality were reported in 6.6% and 12.3% of cases, respectively. Postoperative complications were recorded in 15.2% of patients. Median follow‐up time was 11.4 years. 5‐year and 10‐year OS were respectively 96.0% and 92.9%; 5‐year and 10‐year DFS were respectively 94.6% and 89.0%. Conclusions: Our findings support the oncologic safety and feasibility of OBS in elderly patients, demonstrating acceptable complication rates and oncologic outcomes.

Background: The surrogacy of progression-free survival (PFS) for overall survival (OS) at the trial-level in randomized clinical trials (RCTs) testing immune checkpoint inhibitors (ICIs) in patients with advanced non-small cell lung cancers (NSCLC) is influenced by several clinical-pathological factors. However, potential heterogeneity of PFS surrogacy according to patients’ sex has never been investigated. Methods: RCTs testing ICIs as monotherapy or combined with chemotherapy in patients with advanced NSCLC reporting hazard ratios (HRs) for PFS and OS according to patients’ sex were included. The main objective was to assess sex-based heterogeneity in the trial-level association between PFS (surrogate endpoint) and OS (reference endpoint), overall and in subgroups defined by treatment type (ICIs as monotherapy vs ICIs plus chemotherapy). We used the coefficient of determination (R2) to quantify surrogacy. Results: Twenty RCTs, for a total of 7528 male and 3008 female patients, were included. Overall, the association between OS-HR and PFS-HR was moderate: the R2 from a model adjusted by the type of treatment administered in the experimental arm was 0.69 (95% confidence interval [CI] = 0.34 to 0.88). Sex-disaggregated analysis showed heterogeneity in PFS surrogacy: the association was strong in male patients (adjusted R2 = 0.77; 95% CI = 0.56 to 0.89), but poor in female (adjusted R2 = 0.31, 95% CI = 0.03 to 0.63). Consistent results were obtained in subgroups analyses by treatment type, and in cross-validation analysis. Conclusions: In RCTs testing ICIs alone or combined with chemotherapy in patients with advanced NSCLC, PFS is a robust surrogate endpoint for OS in male patients but not in female.

Background: The surrogacy of overall response rate (ORR) or progression-free survival (PFS) for overall survival (OS) at the trial-level in randomized clinical trials (RCTs) testing antibody-drugs conjugates (ADC) has never been investigated. Methods: RCTs testing ADCs in patients with advanced solid tumors and reporting data on OS and PFS and/or ORR were analyzed. The main objective was to assess the trial-level association between the surrogate endpoints (ORR or PFS) and the reference endpoint (OS), overall and in subgroups of trials defined by tumor type, number of previous lines of systemic treatments, and specific ADC features. Results: Twenty-five RCTs, for a total of 26 treatment comparisons and 11 729 patients, were included in the analysis. In 21 comparisons the ADC was administered as monotherapy, and in 16 was tested in patients with breast cancer. The association between the hazard ratio for OS and relative risk of ORR was moderate: the R2 from a model adjusted by tumor type was 0.47 (95% CI = 0.11 to 0.83). The association between the hazard ratios for OS and PFS was strong: the R2 from the adjusted model was 0.79 (95% CI = 0.66 to 0.92). Cross-validation analyses showed similar results. Consistent results were obtained across all the subgroups analyzed, with the notable exception of the subgroup of trials testing ADCs for breast cancer, where the association between OS and ORR appeared strong (R2 = 0.77; 95% CI = 0.51 to 0.90). Conclusions: In RCTs evaluating ADCs in advanced solid tumors, PFS serves as a robust surrogate endpoint for OS, offering greater reliability than ORR and adequately supporting accelerated approval of ADCs in future trials.

Legends of supplementary figure S1 and S2