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Introduction: Extended-interval (EI) dosing of pembrolizumab (400 mg IV every 6 weeks) was approved across all solid tumors based on pharmacokinetic modeling and exposure-response analyses. Although EI dosing is more convenient for patients, whether the higher dose and extended dosing interval impacts immune-related adverse events (irAE) and clinical outcomes in patients with breast cancer is unknown.

Methods: In this retrospective cohort study, patients with breast cancer treated with pembrolizumab between 2017 and 2024 were included. Safety (irAE) and clinical outcomes including event-free survival (EFS), progression-free survival (PFS) and overall survival (OS) were compared between patients who received only standard-interval (SI) dosing (200 mg IV every 3 weeks) pembrolizumab and those who received ≥ 1 cycle of EI dosing.

Results: Of the 355 patients included, 59 (17%) received ≥ 1 cycle of EI and 296 (83%) received ≥ 1 cycle of only SI. Of those who received ≥ 1 cycle of pembrolizumab EI, 27 (45.8%) started with 200 mg, 7 (11.9%) started with 400 mg, 9 (15.2%) received only 400 mg, and 16 (27.1%) switched between dosing schedules. The majority (71%) of patients had early-stage disease, and 92% had triple-negative breast cancer. In patients with early-stage disease, rates of any-grade irAE were similar (p = 0.3), while grade 3 or higher irAE was lower in EI dosing versus SI (4% vs. 20%; p = 0.01). EFS and OS were similar between the two dosing regimens (p = 0.8 and p = 0.5, respectively). In patients with metastatic disease, any-grade irAE (p = 0.5), grade 3 or higher irAE (p = 0.1), PFS (p = 0.8), and OS (p = 0.5) were similar between the dosing regimens.

Conclusion: In this real-world study in which patients were often switched to EI dosing after initial SI therapy, safety and efficacy of EI dosing were maintained in patients with breast cancer. As more patients are treated with EI dosing, this data provides new evidence that switching to EI dosing is safe and effective, while improving medication burden for patients.

Purpose: Axillary lymph node dissection (ALND) has traditionally been recommended for breast cancer patients with positive sentinel lymph nodes (SLNs). Although omitting ALND is now widely accepted for patients undergoing breast-conserving surgery (BCS) with limited sentinel lymph node biopsy (SLNB) involvement, based on trials such as Z0011, evidence for patients undergoing total mastectomy (TM) remains limited and conflicting. This meta-analysis aimed to evaluate whether ALND can be safely omitted in TM patients with 1-2 positive SLNs by comparing survival outcomes between ALND and SLNB alone groups.

Methods: A systematic search of PubMed, Embase, Cochrane Library, and Web of Science (up to December 2024) identified 29 studies (6 randomized controlled trials and 23 observational) involving a total of 146 407 patients. Survival outcomes, including overall survival (OS), disease-free survival (DFS), and recurrence-free survival (RFS), were pooled using random- or fixed-effects models. Heterogeneity and publication bias were assessed using I2 statistic, Begg's test, and Egger's test. Subgroup analyses were performed based on study design, type of surgical (TM vs. BCS), and pathological T-stage.

Results: Overall, no significant differences in OS (OR = 0.93, 95% confidence interval [CI]: 0.83-1.04), DFS (OR = 1.02, 95% CI: 0.87-1.20), or RFS (OR = 1.08, 95% CI: 0.89-1.30) were observed between ALND and SLNB alone groups. However, in the TM subgroup, ALND was associate with improved OS (OR = 0.75, 95% CI: 0.62-0.90). Similarly, patients with T3-4 tumors demonstrate better OS outcomes with ALND. No significant differences in DFS or RFS were observed across subgroups.

Conclusion: SLNB alone provides comparable survival outcomes to ALND in early breast cancer (EBC) patients with 1-2 positive SLNs, supporting its safety in those undergoing BCS. However, while our analysis suggests a potential survival advantage with ALND in TM patients and those with advanced T-stage (T3-4), this observation requires cautious interpretation due to potential selection bias, residual confounding from unmeasured variables and confounding by indication where ALND may reflect more intensive multimodal therapy rather than causally improving OS. Therefore, these subgroup findings should not be considered practice-changing at this stage. Further high-quality prospective studies are warranted to validate these associations and optimize patient selection criteria.

Background: Metastatic colorectal cancer (mCRC) remains a leading cause of cancer-related mortality. While metastasectomy could improve survival in selected patients, the role of repeated resections in oligorecurrent disease is less defined.

Methods: We retrospectively analyzed patients with mCRC treated at Fondazione Policlinico Universitario Agostino Gemelli-IRCCS (Rome, Italy) between 2010 and 2024. Eligible patients underwent ≥2 resections of metastatic lesions. Disease-free survival after second metastasectomy (DFS2) and overall survival (OS) were the coprimary end points. Prognostic factors were tested with Cox regression, and a composite risk score (Fondazione Policlinico Gemelli Risk Score [FPGRiskScore]) was developed.

Results: Among 1586 patients with mCRC, 396 (24.9%) received at least one metastatic surgery and 143 (9%) underwent ≥2 metastasectomies. Median DFS2 was 8.2 months (95% confidence interval [CI]: 7.3-13.1), and 5-years OS rate was 73.1% (95% CI: 64.5-83.0); after a median follow-up from the last metastasectomy of 34.3 months, 49/143 patients (34.2%) were relapse-free and median DFS after the second surgery of the metastases from the last surgery was 13.1 months (95% CI: 9.1-17.5). Patients stratified by FPGRiskScore (disease-free interval [DFI] from the first metastasectomy ≤ vs. >12 months, metastatic burden ≤ vs >5 cm, RAS/BRAF status, and Eastern Cooperative Oncology Group Performance Status [ECOG PS] scale 0 vs. ≥1) showed distinct outcomes: low-risk patients achieved a median DFS2 of 18.4 months and 5-years OS of 87.6%, compared with 7.8 months/72.0% in intermediate-risk and 4.9 months/55.3% in high-risk group.

Conclusions: Repeated metastasectomy offers substantial survival benefit in selected patients with oligorecurrent mCRC, with long-term disease control achievable in a subset. Prognostic stratification incorporating clinical and molecular features (FPGRiskScore) may refine patient selection and guide multidisciplinary management.

Background: Limited data are available on estradiol (E2) levels during fulvestrant treatment in women with hormone receptor-positive breast cancer.

Methods: We measured plasma E2 levels in women receiving fulvestrant using liquid chromatography-tandem mass spectrometry. Patient characteristics and treatment efficacy were assessed in relation to E2 levels. A cutoff of 2.72 pg/mL was used because it defines E2 suppression and postmenopausal status.

Results: A total of 69 women were enrolled, with a median age of 48 years. The median duration of fulvestrant treatment was 11.6 months. The median E2 level across the cohort was 3.60 pg/mL, with considerable interindividual variability (range: 1.11-526.13 pg/mL), and 49 women (71.0%) had E2 levels above 2.72 pg/mL. Eleven women (15.9%) had premenopausal E2 levels (>10 pg/mL). During a median follow-up period of 8.4 months, there was no statistically significant difference in progression-free survival (PFS) between women with E2 levels >2.72 pg/mL and those with E2 levels ≤2.72 pg/mL (P = .391). However, among women who benefited from first- or second-line fulvestrant therapy (PFS > 6 months), those with E2 levels >2.72 pg/mL exhibited significantly poorer PFS compared to those with E2 levels ≤2.72 pg/mL (P = .043).

Conclusions: These findings support the need for E2 monitoring in women receiving fulvestrant therapy to better assess E2 status and its association with treatment efficacy.

Importance: Avelumab maintenance therapy improves survival in patients with advanced urothelial carcinoma who respond to first-line platinum-based chemotherapy. However, real-world evidence on its effectiveness and on the prognostic value of baseline clinical factors remains limited.

Objective: To evaluate the real-world effectiveness of Avelumab maintenance therapy and to identify baseline prognostic factors associated with clinical outcomes.

Design: Multicenter prospective observational study including a retrospective cohort of patients treated before study initiation.

Setting: Several Italian oncology centers participating between 2021 and 2023.

Participants: A total of 251 patients with advanced or metastatic urothelial carcinoma who received Avelumab maintenance therapy after achieving disease control with first-line platinum-based chemotherapy.

Intervention(s) or exposure(s): Avelumab maintenance therapy administered according to clinical practice. Baseline clinical variables, including ECOG performance status, metastatic sites, and corticosteroid use, were assessed for prognostic significance.

Main outcome(s) and measure(s): Primary outcomes were overall survival (OS) and progression-free survival (PFS). Secondary outcomes included overall response rate (ORR) and disease control rate (DCR). Prognostic factors were evaluated using multivariate Cox regression.

Results: Median OS was 22.4 months, and median PFS was 7 months. The ORR and DCR were 26.75% and 69.30%, respectively. Independent predictors of worse OS were ECOG ≥1 (HR 1.57), bone metastases (HR 1.88), brain metastases (HR 7.02), and baseline corticosteroid use (HR 2.42). An exploratory prognostic score integrating ECOG status, bone metastases, and steroid use stratified patients into three groups with significantly different outcomes: median OS was 39.9 months (no adverse factors), 14.1 months (one factor), and 8.4 months (two or more factors), with corresponding ORRs of 33.6%, 28.0%, and 6.9%.

Conclusions and relevance: In this large real-world cohort, Avelumab maintenance confirmed its effectiveness and safety in advanced urothelial carcinoma. A simple exploratory prognostic score based on ECOG performance status, bone metastases, and baseline corticosteroid use successfully stratified patients by survival outcomes and may support personalized treatment strategies in clinical practice.

Introduction: FoundationOne®CDx (F1CDx) and Oncomine Dx target test (ODxTT) are commercially available oncology biomarker assays that apply different next-generation sequencing methodologies used to identify predictive markers for therapy selection in non-small cell lung cancer (NSCLC). We hypothesized that F1CDx can detect a higher number of actionable alterations compared with the ODxTT assay.

Materials and methods: We compared the prevalence of genomic alterations (GA) in a real-world NSCLC cohort tested by F1CDx to the theoretical detection by ODxTT, based on publicly available coverage specifications. The clinical actionability of GA was assessed based on NCCN treatment guidelines and FDA oncology drug approvals.

Results: KRAS G12C, EGFR mutations, and MET mutations were among the most frequent actionable alterations detected in a large genomic dataset of NSCLC data assayed by the F1CDx test. The ODxTT specifications indicate that ODxTT detects all BRAF and KRAS FDA-approved alterations detected by F1CDx and subsets of the following clinically significant markers: EGFR 83%, RET 76%, ROS1 74%, and ERBB2 38%. In addition, ODxTT had no coverage for actionable genomic findings in ALK, MET, NTRK1/2/3, TMB, or MSI-High status. In this study, the ODxTT assay may fail to report at least one of the clinically actionable biomarkers in 42% of tissue samples compared to F1CDx.

Discussion: In summary, in advanced NSCLC, hybrid capture-based NGS, such as F1CDx, may capture more actionable genomic alterations as compared with ODxTT, an amplicon-based NGS.

Background: The increasing reliance on accelerated approvals and surrogate endpoints for Food and Drug Administration (FDA) approvals of gastrointestinal (GI) cancer therapies raises concerns about their clinical benefit and long-term patient outcomes. The shift toward single-arm trials in regulatory decisions further complicates treatment evaluation.

Material and methods: This retrospective observational study evaluated all FDA approvals for GI cancer therapies from January 2006 through January 2025. Data were extracted from FDA archives, ClinicalTrials.gov, and PubMed. Approvals were categorized by regulatory pathway (accelerated vs regular), trial design (single-arm vs randomized), and primary endpoint (surrogate vs overall survival [OS]). Clinical benefit was assessed based on OS improvement and the European Society for Medical Oncology Magnitude of Clinical Benefit Scale (ESMO-MCBS). The primary outcome was the proportion of approvals based on surrogate versus OS endpoints. Secondary outcomes included use of single-arm designs, frequency of accelerated approvals, OS gain, and the proportion meeting ESMO-MCBS substantial benefit (score ≥ 4).

Results: The FDA granted 60 GI cancer drug approvals from 67 trials. Approvals rose from 15 (25%) in 2006-2014 to 45 (75%) in 2015-2025. Single-arm trials increased to 24%, and surrogate endpoints were used in 41.8% (ORR 20.9%, PFS 19.4%). Median OS improvement was 2.1 months (IQR: 1.6-2.65). Only 24.3% of trials met ESMO-MCBS substantial benefit. Of 15 accelerated approvals, 66.7% remained pending, 13.3% received full approval, and 20% were withdrawn.

Conclusion: Expedited approvals have improved drug access in GI oncology, but modest benefits highlight the need to balance speed with outcomes that truly matter to patients.

Introduction: Prior studies have shown mixed findings regarding the relationship between prognostic awareness with quality of life (QOL) and psychological distress in patients with advanced cancer. Prognostic awareness is a multidimensional construct including a cognitive component (ie, the ability to understand one's life-limiting illness) and an emotional coping component (ie, the capacity to process terminal prognosis). Yet, it remains unclear which domains of prognostic awareness are associated with QOL and psychological distress.

Materials and methods: We conducted a cross-sectional study of adults with metastatic solid tumors treated with noncurative intent at a single academic center from 11/2019 to 6/2022. We used the Prognostic Awareness Impact Scale (PAIS) to measure components of prognostic awareness, including the cognitive and emotional coping components. We used the Functional Assessment of Cancer Therapy-G and Hospital Anxiety and Depression Scale to measure QOL and psychological distress, respectively. Linear regression models were used to examine the relationship between the PAIS domains and patient-reported outcomes.

Results: We enrolled 61.9% (632/1021) of eligible patients. Cognitive understanding of prognosis was not associated with QOL (B = -2.3, P = .114), anxiety (B = 0.7, P = .057), or depression symptoms (B = 0.4, P = .293). However, higher emotional coping with prognosis was associated with better QOL (B = 1.7; P < .001), lower anxiety (B = -0.6; P < .001), and depression (B = -0.3; P < .001).

Conclusion: Patients' emotional coping with their prognosis, rather than cognitive acknowledgment of their incurable cancer, was associated with QOL and psychological distress. Our findings underscore patients' ability to tolerate an accurate understanding of their prognosis and the critical need to incorporate effective coping strategies during prognostic discussions.

Background: Erdafitinib is approved for locally advanced/metastatic urothelial cancer (LA/mUC). As enfortumab vedotin (EV) plus pembrolizumab enters frontline management, outcomes with erdafitinib pre- and post-EV are clinically relevant but not specifically evaluated in clinical trials.

Methods: UNITE is a multi-institutional retrospective study of patients with LA/mUC treated with novel targeted agents. All patients with FGFR3 alterations treated with EV only, erdafitinib then EV (Erda->EV), and EV then erdafitinib (EV->Erda) were included. Sequential treatment with EV and Erda was not required. Primary endpoints were observed response rates (ORR) and progression-free survival (PFS); secondary endpoint was overall survival (OS).

Results: We identified 83 patients with FGFR3 alterations and separated them into three cohorts: EV only (n = 44), Erda->EV (n = 24), and EV->Erda (n = 15). Most (72%) received ≥2 lines of therapy before erdafitinib (checkpoint inhibitor [87%], platinum-based chemotherapy [64%]). Median PFS with erdafitinib for EV-naïve cohort was 7.5 months and in EV-treated cohort 4.0 months (HR 0.78; 95% CI 0.35-1.7). ORR with erdafitinib for EV-naïve was 33% and EV-treated 31% (OR 1.1; 95% CI 0.29-4.1). Median PFS with EV for patients who were erdafitinib-naïve was 6 months and in erdafitinib-treated 5.3 months (HR 0.61; 95% CI 0.34-1.09). ORR with EV was 54% in erdafitinib-naïve cohort and 32% in erdafitinib-treated cohort (OR 2.5; 95% CI 0.87-6.3).

Conclusion: In patients with FGFR3-altered LA/mUC, erdafitinib is active pre- and post-EV. Outcomes with erdafitinib were consistent with clinical trial data generated prior to broader frontline use of EV. Findings are hypothesis-generating and given small sample size should be interpreted with caution.