Search Results (416)

Immunotherapy with immune checkpoint inhibitors (ICIs) has profoundly transformed the therapeutic landscape of lung cancer. Although ICIs are generally associated with a more favorable toxicity profile compared with traditional chemotherapy, rare and potentially severe immune-related adverse events (irAEs) may occur, sometimes posing significant diagnostic challenges. We report a case of macrophage activation syndrome (MAS) following a single administration of the anti-PD-L1 antibody atezolizumab in a patient with advanced non-small-cell lung cancer (NSCLC). A 62-year-old woman was diagnosed in February 2024 with stage IIIB NSCLC according to the 8th TNM classification. The patient was deemed ineligible for radiotherapy because of previous thoracic irradiation for breast cancer. First-line therapy with carboplatin plus pemetrexed was administered from March to June 2024, resulting in stable disease; this was followed by pemetrexed maintenance from July to October 2024, at which time thoracic disease progression was documented. Second-line treatment with atezolizumab was initiated in November 2024. Ten days after the first infusion, the patient was admitted to the emergency department for fever and confusion. Laboratory investigations revealed markedly elevated C-reactive protein and hyperferritinemia. Despite empirical antibiotic therapy, fever and thrombocytopenia persisted. Bone marrow biopsy demonstrated findings consistent with MAS. Corticosteroid therapy with prednisone at 1 mg/kg was promptly initiated under rheumatologic supervision, leading to a rapid clinical and biochemical improvement. During tapering, inflammatory markers relapsed when prednisone was reduced to below 12.5 mg/day. Given the occurrence of a grade 4 (CTCAE v5.0) immune-related adverse event, atezolizumab was permanently discontinued. The patient remains in follow-up without radiological evidence of disease progression. This case highlights the diagnostic challenge of MAS secondary to ICIs, which may initially present with nonspecific symptoms such as fever, confusion, and elevated inflammatory markers. Early recognition and timely initiation of high-dose corticosteroids were essential for effective management and full recovery. Clinicians should maintain a high index of suspicion for MAS among rare but severe hematologic irAEs during immunotherapy. Full article

Docetaxel has been a standard second-line or later (2L+) treatment for advanced non-small cell lung cancer (NSCLC) for more than two decades and remains recommended in current treatment algorithms. However, real-world outcomes in the era of immune checkpoint inhibitors (ICI) are limited. This multicenter retrospective study included patients with advanced NSCLC treated with 2L+ docetaxel monotherapy between January 2011 and December 2020. The primary endpoint was median overall survival (mOS) from docetaxel initiation. Subgroup analyses were conducted to identify predictors of OS. A total of 285 patients were analyzed. Median age was 62 years; 43% female, 75% ECOG performance status (PS) 0–1, and 65% adenocarcinoma. Molecular alterations included EGFR (20%) and KRAS (15%). PD-L1 status was available in 66% of patients. Median docetaxel exposure was three cycles, administered as 2L (48%), 3L (35%), or 4L+ (17%). Prior therapies included chemotherapy (96%), ICI (38%), targeted therapy (21%), and chemo-immunotherapy (10%). mOS was 6.5 months (95% CI, 5.9–7.3). On multivariate analysis, KRAS alteration (HR 0.59; 95% CI 0.37–0.94; p = 0.026) and ECOG PS (1 vs. 0 HR 2.26; 95% CI 1.15–4.43; p = 0.018, ≥2 vs. 0 HR 2.62; 95% CI 1.27–5.41; p = 0.0091) remained independent predictors of OS. Real-world OS with docetaxel is consistent with historical trial data, irrespective of prior ICI, targeted therapy, or chemo-immunotherapy. KRAS mutation and a favourable ECOG PS were associated with improved survival. Full article

Background and Clinical Significance: Colorectal cancer (CRC) is the third most common cancer worldwide and the second leading cause of cancer-related death. Skeletal muscle metastases are extremely rare and typically occur in advanced or poorly differentiated tumors. In selected oligometastatic cases, surgical excision can provide symptom relief and requires a multidisciplinary approach. Case Presentation: We report a 73-year-old female patient with colonic adenocarcinoma treated with right hemicolectomy and side-to-side mechanical anastomosis, followed by adjuvant CAPOX chemotherapy. The tumor was characterized by MSI-H (microsatellite instability-high) status. During adjuvant treatment (less than 6 months after surgery), she developed progressive right thigh pain, later diagnosed as an intramuscular skeletal muscle metastasis measuring approximately 16 × 13 × 8 cm. The patient underwent en bloc resection of the tumor, followed by adjuvant chemotherapy after metastasectomy. Upon disease progression, first-line chemotherapy in combination with targeted therapy (bevacizumab) was administered. Conclusions: Skeletal muscle metastases from colorectal adenocarcinoma are rare. This case emphasizes the importance of recognizing atypical metastatic patterns and suggests that, in selected oligometastatic cases, surgical excision combined with a multidisciplinary approach may improve symptom control and clinical outcomes. Full article

Background: High-risk cytogenetic multiple myeloma (HRMM) confers inferior outcomes despite significant therapeutic advances. Real-world data characterizing contemporary treatment patterns across lines of therapy in this population are limited. Methods: We conducted a multicenter retrospective study of 205 patients with HRMM diagnosed between January 2009 and January 2024. High-risk cytogenetics were defined according to the International Myeloma Working Group (IMWG) and Revised International Staging System (R-ISS) criteria as the presence of del(17p), t(4;14), t(14;16), t(14;20), and/or gain/amplification of 1q21. Treatment regimens were categorized by the number of agents (doublet, triplet, quadruplet), mechanism of action (proteasome inhibitor [PI]-based, immunomodulatory drug [IMiD]-based, and anti-CD38 monoclonal antibody-based), and specific regimen composition. Treatment patterns were analyzed across three treatment eras and stratified by age (<70 vs. ≥70 years). Results: The cohort included 205 patients (median age, 62 years [interquartile range [IQR], 54–68 years]; 78.5% aged <70 years). Double-hit and triple-hit cytogenetics were present in 60.0% and 7.3% of patients, respectively. For first-line induction, triplet therapy predominated (81.0%, n = 166), followed by quadruplet (8.8%, n = 18), doublet (5.9%, n = 12), and multi-agent chemotherapy (2.9%, n = 6). By mechanism of action, PI + IMiD combinations were the most common (63.4%, n = 130), followed by PI-based (19.0%, n = 39), anti-CD38-based (10.2%, n = 21), and IMiD-based (2.9%, n = 6) regimens. Era-stratified analysis revealed a significant increase in quadruplet utilization from 3.2% in Era 1 (2009–2015) to 20.3% in Era 3 (2020–2024), with anti-CD38-containing frontline regimens administered to 26.6% of patients in the contemporary era (p < 0.001). Second-line induction was required in 50 patients (24.4%), with anti-CD38-based triplets comprising the most common approach (30.0%). Autologous stem cell transplantation (ASCT) was performed in 75.1% of patients overall, with significantly higher utilization in those aged <70 years (83.9% vs. 43.2%). Maintenance therapy was administered to 71.7% of patients (n = 147), with IMiD-based regimens predominating (53.1%), followed by PI + IMiD combinations (27.9%) and anti-CD38-containing regimens (10.2%). Despite intensive therapy, 69.4% of patients on maintenance experienced disease relapse, with higher rates observed in younger patients (74.8% vs. 41.7%). Conclusions: In this real-world HRMM cohort, the PI + IMiD triplet regimen remained the predominant induction approach, with a significant shift toward quadruplet and anti-CD38-containing regimens in the contemporary era. However, substantial relapse rates during maintenance underscore the continued unmet need in HRMM and support the early integration of novel therapeutic strategies, including quadruplet induction and BCMA-directed agents, in this population. Full article

Background: De novo (pretreatment) EGFR T790M mutation is a rare molecular finding in non-small cell lung cancer (NSCLC) and has historically been associated with primary resistance to first- and second-generation EGFR tyrosine kinase inhibitors (TKIs). Evidence guiding optimal first-line management in this subgroup, particularly in elderly patients, remains limited. Case Presentation: We report a case of an elderly patient with treatment-naïve advanced non-squamous NSCLC harboring a concurrent EGFR exon 19 deletion and de novo EGFR T790M mutation. Given the patient’s age, significant cardiopulmonary comorbidities, and absence of rapidly progressive disease, a multidisciplinary tumor board recommended first-line osimertinib monotherapy. Treatment was well tolerated, with rapid improvement in performance status and no clinically significant adverse events. Serial contrast-enhanced CT restaging demonstrated RECIST 1.1–defined stable disease, without development of new visceral, nodal, cerebral, or osseous metastases. The patient remains on continuous osimertinib therapy with durable disease control at the time of manuscript preparation. Conclusion: Primary EGFR T790M–positive NSCLC can achieve durable disease control with first-line osimertinib, even in advanced age. While combination strategies with chemotherapy may improve survival outcomes in selected patients, treatment decisions in elderly individuals must carefully balance efficacy, toxicity, and quality of life. Chronological age alone should not discourage active targeted treatment when guided by molecular profiling and comprehensive clinical assessment. Full article

Epidermal growth factor receptor (EGFR) exon 20 insertion (ex20ins) mutations are the third most common EGFR mutation subtype in non-small cell lung cancer (NSCLC), accounting for approximately 4–12% of all EGFR-mutated cases. Unlike classical EGFR mutations, ex20ins mutations confer inherent resistance to first-, second- and third-generation EGFR tyrosine kinase inhibitors (TKIs) due to unique structural alterations that lock the αC-helix in an active orientation, creating steric hindrance within the drug-binding pocket. Until recently, platinum-based chemotherapy remained the standard first-line treatment, with objective response rates (ORR) of 19–47% and a median progression-free survival (PFS) of 6–7 months. Over the past five years, the therapeutic landscape has shifted, driven by the development of selective inhibitors and bispecific antibodies. Amivantamab, a bispecific EGFR–mesenchymal–epithelial transition factor (MET) antibody combined with chemotherapy, demonstrated superior efficacy in the PAPILLON trial, with an ORR of 73% and a median PFS of 11.4 months in the first-line setting. Sunvozertinib, an oral, selective EGFR inhibitor, received U.S. Food and Drug Administration (FDA) accelerated approval in 2025, with an ORR of 46% and a median duration of response (DOR) of 11.1 months in platinum-pretreated patients. Emerging therapies, including zipalertinib and furmonertinib, have shown promising results in early-phase trials, with zipalertinib demonstrating activity in patients pretreated with amivantamab (ORR 31.5%) and furmonertinib achieving remarkable responses in treatment-naive patients (ORR 78.6% at 240 mg). This comprehensive review analyzes the molecular biology, structural mechanisms, current therapeutic options, and novel investigational agents for EGFR ex20ins-mutated NSCLC. Full article

Background/Objectives: The aim of the study was to evaluate the real-world effectiveness of immunotherapy compared to chemotherapy in advanced non-small-cell lung cancer (NSCLC) and assess molecular profiling patterns in a large Greek cohort. Methods: This was a retrospective study of patients with advanced NSCLC from three oncology centers. Clinical, pathological, and/or molecular data were collected from the patient medical records. The primary endpoint was overall survival (OS). Results: Overall, 684 patients with advanced NSCLC were included; median age 67 years (range, 33 to 89). More than half of the patients (406, 59.4%) had been diagnosed with de novo metastatic disease. Overall, 289 of 684 (42.3%) patients underwent tumor molecular profiling. Immunotherapy use, with or without chemotherapy, in the first-line setting increased significantly over time (p < 0.001). Among 610 patients eligible for outcome analysis, immunotherapy at any line of treatment was associated with increased OS compared to chemotherapy alone (17.5 vs. 8.6 months; HR: 0.51, 95% CI: 0.42, 0.61; p < 0.001). The results remained consistent with the primary analysis as well as the landmark analysis using a 3-month cutoff to account for the immortal-time bias. Furthermore, time to next treatment (TTNT) was significantly longer with immunotherapy use in both first- and second-line treatment (TTNT1: 10.0 vs. 6.8 months, HR: 0.45, 95% CI: 0.34, 0.58; p < 0.001; TTNT2: 6.7 vs. 5.9 months, HR: 0.59, 95% CI: 0.40, 0.87; p = 0.009). Immunotherapy use remained an independent predictor of improved survival (HR: 0.50, 95% CI: 0.40, 0.63; p < 0.001). Conclusions: Immunotherapy, with or without chemotherapy, significantly improved clinical outcomes compared to chemotherapy alone in a real-world cohort of patients with advanced NSCLC. While molecular testing rates increased significantly over the study, only a minority of patients underwent PD-L1 testing, while broad molecular profiling was also incomplete, limiting the interpretation of treatment effects. Improvements to guarantee the universal molecular testing of patients with NSCLC are warranted. Full article

Antibody–drug conjugates (ADCs) are reshaping the therapeutic approach to advanced gastrointestinal cancers by integrating tumor-specific monoclonal antibodies with potent cytotoxic payloads to improve targeted tumor cell destruction while minimizing systemic exposure. Compared to traditional chemotherapy, trastuzumab deruxtecan has significantly improved objective response rates and overall survival in HER2-positive gastric and gastroesophageal junction tumors after trastuzumab-based therapy. This supports its role as an important second-line or later treatment option. The ongoing advancement of ADCs targeting CLDN18.2, TROP2, and CEACAM5 indicates that this therapeutic category will continue to expand across gastrointestinal neoplasms. Nonetheless, these advancements are accompanied by a specific and clinically significant toxicity profile. Hematologic suppression, gastrointestinal side effects, hepatotoxicity, and notably interstitial lung disease (ILD) are essential consequences that may need inpatient assessment and care. Interstitial lung disease (ILD), although uncommon, may be severe or lethal if not identified immediately and treated swiftly with medication cessation and corticosteroids. In hospitalized patients, distinguishing ADC-related toxicity from infection or disease progression is often difficult owing to overlapping clinical manifestations, requiring meticulous evaluation and interdisciplinary cooperation. As ADCs are integrated into earlier treatment lines and across a broader patient population, hospital systems must evolve to ensure prompt identification, consistent management protocols, and efficient collaboration between oncology and inpatient teams. This study analyzes the mechanisms, clinical effectiveness, and safety profile of ADCs in gastrointestinal oncology, pointing out the importance of institutional preparedness to safely incorporate these medicines into standard clinical practice. These features also align ADC therapy with personalized medicine by emphasizing biomarker-guided patient selection and individualized toxicity monitoring. Full article

Background and Objectives: Cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) combined with endocrine therapy are recommended as first- or second-line treatment for hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced or recurrent breast cancer. However, in clinical practice, initiation timing varies according to patient characteristics, prior treatments, and the choice of the physician. Thus, the optimal timing of combination treatment remains unclear. Materials and Methods: In this multicenter retrospective cohort study, we reviewed 66 female patients who received CDK4/6i (palbociclib or abemaciclib) between March 2018 and November 2019. Patients were categorized into the first-line treatment (group A) (n = 21) and second- or subsequent-line treatment (group B) (n = 45) groups. In the latter group, endocrine therapy and/or chemotherapy had been administered previously. Duration of treatment with CDK4/6i (DOT), overall survival (OS), treatment duration of other regimens, and reasons for treatment discontinuation after CDK4/6i treatment were compared between groups. Results: The median DOT was significantly longer in group A than in group B (23 months (95% CI, 8–43) vs. 7 months (95% CI, 3–15); p = 0.015, at log-rank test). OS showed no significant difference between the two groups (p = 0.69, at log-rank test). Conclusions: In patients with HR-positive, HER2-negative advanced or recurrent breast cancer, first-line use of CDK4/6 inhibitors was associated with a significantly longer duration of treatment compared with second- or subsequent-line use. However, no significant difference in OS was observed between patients receiving CDK4/6 inhibitors as first-line or second- or subsequent-line therapy. Full article

Cholangiocarcinoma (CCA) is a highly lethal, heterogeneous malignancy arising from the biliary tract. Although the prevalence of CCA is relatively low, its incidence has increased in the last few decades, and the overall prognosis is poor. Surgical resection remains the most efficacious treatment modality for CCA. However, due to its aggressive nature and often asymptomatic presentation, most patients are first diagnosed with advanced disease, precluding them from curative intervention. Moreover, due to its heterogeneity at the molecular, genomic, and epigenetic levels, drug treatment of CCA remains challenging. In this review, we discuss the current standard drug treatment approaches, recent breakthroughs, and promising new therapeutics for CCA. We summarize key clinical data for the standard first-line chemotherapy regimen and its efficacy and resistance mechanisms, along with more recent studies supporting or proposing second-line treatments. We highlight landmark clinical trials, including ABC-02, which established gemcitabine-cisplatin (GC) as the first-line regimen against biliary cancers. Additionally, we discuss recent findings on the susceptibility of CCA against targeted therapies and other immunologic molecules, including results from the KEYNOTE-966 and TOPAZ-1 clinical trials. Finally, we critically analyze new therapeutics in the preclinical and clinical space, such as CAR-T cells and oncolytic viruses that may be effective against CCA. Full article

Introduction: Chemotherapy-induced peripheral neuropathy (CIPN) is a dose-limiting toxicity affecting many patients treated with neurotoxic agents, leading to persistent pain and impaired quality of life. Methods: In our trial, Trial ID: NCT06091553, 160 patients met the eligibility criteria and were randomized into three groups. First, Arm D (duloxetine). Second, Arm (D + A): duloxetine is augmented with amitriptyline. Third, Arm (D + G): duloxetine is augmented with gabapentin. The primary outcome is the difference in Pain Inventory—Short Form (BPI-SF) measured during the final follow-up week (Week 4 and Week 8) between the treatments. Results: All groups showed significant within-group reductions in pain scores from baseline to Weeks 4 and 8. Meanwhile, all groups exhibited numerical improvements for the average pain by Week 8. No statistically significant differences were found between groups at either Week 4 (p = 0.161) or Week 8 (p = 0.868). Similarly, the proportion of responders was comparable across treatment arms at both time points, with 74.5–82.8% achieving a clinically meaningful reduction in pain by Week 8 (p = 0.566). Conclusions: These findings support duloxetine as an evidence-based first-line therapy for painful CIPN, while combination regimens may be reserved for individualized use in patients with inadequate response, pending confirmation in larger multicenter trials. Full article

Background: Vandetanib and cabozantinib are the approved first-line antiangiogenic multikinase inhibitors (aaMKIs) for metastatic medullary thyroid carcinoma (MTC); however, real-world data on their comparative efficacy, optimal sequencing, and outcomes beyond the first-line setting remain limited. We report multicenter real-world outcomes from a large Turkish cohort. Methods: In this retrospective multicenter cohort study, we analyzed data from 24 oncology referral centers across Türkiye. Patients with histologically confirmed metastatic MTC who received systemic therapy between December 2011 and December 2024 were included. The primary endpoint was progression-free survival (PFS), assessed separately for first-line (PFS1) and second-line (PFS2) therapy. Overall survival (OS) and prognostic factors were evaluated using Kaplan–Meier and Cox proportional hazards analyses. Results: A total of 115 patients were included (median age 47.4 years; 63.5% male). In the first-line setting, vandetanib (47.8%) and cabozantinib (30.4%) were the most frequently used agents. Median PFS1 was 40.8 months with vandetanib and was not reached with cabozantinib; both were significantly superior to chemotherapy (median PFS1 4.9 months; log-rank p < 0.001). In the second-line setting, median PFS2 was not reached with cabozantinib and was 32.5 months with vandetanib. Sequential use of cabozantinib and vandetanib across the first two lines was associated with a median time to second progression of 114 months, compared with 39 months in patients receiving any other TKI combination (p = 0.003). Second-line use of cabozantinib or vandetanib was independently associated with improved OS (HR 0.40, 95% CI 0.16–0.98; p = 0.046). On multivariate analysis, younger age (HR 0.16, 95% CI 0.03–0.72; p = 0.017) and bone metastasis (HR 0.29, 95% CI 0.11–0.73; p = 0.009) were independent prognostic factors for OS. Conclusions: In this real-world cohort of patients with metastatic MTC, cabozantinib and vandetanib demonstrated durable efficacy across treatment lines, substantially outperforming alternative TKIs and chemotherapy. Sequential use of both approved aaMKIs was associated with prolonged disease control. These findings suggest a potential association between access to both agents and improved outcomes. They are consistent with their central role in treatment sequencing, particularly in settings with limited access to selective RET inhibitors. Given the retrospective design and small subgroup sizes, these results should be interpreted as exploratory and hypothesis-generating. Full article

Background and Objectives: Non-small cell lung cancer (NSCLC) accounts for approximately 85% of all lung cancers and remains a leading cause of cancer-related mortality worldwide. EGFR-targeted tyrosine kinase inhibitors (TKIs) have substantially improved outcomes in EGFR-mutant NSCLC; however, primary and acquired resistance continues to limit their long-term efficacy. HER3 (receptor tyrosine-protein kinase ErbB3), a member of the ErbB receptor family, has been implicated in TKI resistance through heterodimerization with EGFR and HER2, leading to downstream PI3K/AKT pathway activation. Despite its biological plausibility as a resistance mediator, the clinical significance of HER3 expression as a prognostic and predictive biomarker in EGFR-mutant NSCLC has not been thoroughly characterized in real-world cohorts. Materials and Methods: This retrospective, single-center study included 52 patients diagnosed with EGFR-mutant NSCLC who received TKI therapy at Afyonkarahisar Health Sciences University between January 2011 and September 2023. HER3 protein expression was evaluated by immunohistochemistry (IHC) on formalin-fixed, paraffin-embedded tumor tissue sections using the Huabio anti-HER3 antibody (clone PD00-44, 1:2000 dilution). Staining in more than 30% of tumor cells was considered HER3-positive; membranous staining intensity was scored on a 1–3 scale. Progression-free survival (PFS1, PFS2) and overall survival (OS) were analyzed using the Kaplan–Meier method and log-rank test. Statistical significance was set at p < 0.05. Results: Of 52 patients (55.8% female; mean age 64.5 years), 59.6% received chemotherapy and 40.4% received an EGFR TKI as first-line treatment; erlotinib constituted 71.2% of targeted therapies. In the first-line TKI group, HER3-negative patients had a numerically longer median PFS1 compared with HER3-positive patients (14.0 vs. 7.1 months; p = 0.285); however, this difference did not reach statistical significance and should be interpreted with caution given the small sample size. In contrast, among patients receiving first-line chemotherapy, HER3 staining status did not meaningfully affect PFS1 (4.1 vs. 2.5 months; p = 0.063). In second-line treatment, HER3-positive patients who received TKI after prior chemotherapy demonstrated a PFS2 comparable to or slightly exceeding that of HER3-negative patients (21.8 vs. 19.8 months; p = 0.49), suggesting that the sequencing of chemotherapy before TKI may attenuate the adverse effect of HER3 positivity. Median OS was 15.1 months in HER3-negative patients and 12.7 months in HER3-positive patients (p = 0.824); this numerical difference of approximately 3 months did not reach statistical significance and should therefore be interpreted cautiously. Among patients receiving TKI in the first line, HER3-positive patients had a shorter median OS than HER3-negative patients (9.6 vs. 14.2 months), whereas those receiving TKI in the second line showed a trend toward longer OS in HER3-positive patients (20.5 vs. 17.2 months). Conclusions: HER3 expression was associated with reduced first-line TKI efficacy in EGFR-mutant NSCLC, suggesting a possible role for HER3 in primary TKI resistance; however, these findings are exploratory and did not reach statistical significance. The observation that HER3-positive patients who received chemotherapy before TKI demonstrated outcomes comparable to HER3-negative patients raises the hypothesis that treatment sequencing may potentially influence the impact of HER3 positivity, though this requires prospective validation before any clinical conclusions can be drawn. These results suggest that HER3 expression may warrant further investigation as a candidate biomarker for treatment sequencing decisions and as a potential therapeutic target in EGFR-mutant NSCLC. Prospective studies evaluating chemotherapy–TKI sequencing and HER3-directed agents such as patritumab deruxtecan (HER3-DXd) in HER3-positive patients are needed to confirm these preliminary observations. Full article

Background/Objectives: Several chemotherapeutic regimens and targeted therapies are currently established as standard second-line treatments for patients with advanced biliary tract cancer (BTC). However, evidence regarding the benefits of treatment after first-line therapy failure remains limited, particularly among Thai populations. This study aimed to explore the efficacy of second-line chemotherapy in patients with advanced BTC. Methods: We conducted a single-institution, retrospective study including patients with locally advanced or metastatic BTC who experienced disease progression following first-line treatment between January 2017 and December 2019. Overall survival (OS) was defined as the primary endpoint. The secondary endpoint was the restricted mean survival time (RMST). To minimize confounding, propensity scores were estimated and applied using inverse probability of treatment weighting (IPTW). Results: A total of 110 patients were included, of whom 69 (62%) received second-line chemotherapy in combination with best supportive care (2LCMT + BSC), while 41 (38%) received best supportive care (BSC) alone. The majority of cases were intrahepatic cholangiocarcinoma (73.9% and 70.7% in each group, respectively). The median OS was 5.3 months (95% CI 3.5–7.0) in the 2LCMT + BSC group and 1.0 months (95% CI 0.5–1.9) in the BSC-only group (unadjusted HR 0.40, 95% CI 0.26–0.59; p < 0.001). In IPTW-adjusted flexible parametric regression analysis, second-line chemotherapy was associated with a 53% reduction in the risk of death compared with BSC alone (p = 0.009). The restricted mean survival time (RMST) differences between groups at 3, 6, and 12 months were 1.3 months (95% CI 0.9–1.6; p < 0.001), 2.6 months (95% CI 1.9–3.3; p < 0.001), and 3.9 months (95% CI 2.7–5.1; p < 0.001), sequentially. Conclusions: These findings demonstrate that second-line chemotherapy provides a significant overall survival benefit compared with best supportive care alone in patients with advanced BTC. Full article

Background: This study describes treatment patterns and clinical outcomes in patients with advanced urothelial carcinoma (aUC) in the US following the approval of avelumab for first-line maintenance treatment. Methods: This retrospective cohort study used deidentified patient data from the Tempus database. Eligible patients had completed first-line systemic anticancer treatment for aUC between July 2020 and March 2023. Results: In total, 974 eligible patients were identified; most (72%) were male. Median age at diagnosis was 70 years. Among patients who completed first-line platinum-based chemotherapy (644 [66%]), 574 (89%) had no evidence of disease progression. Of 219 patients who received first-line maintenance, 135 (62%) received avelumab. Median (95% CI) overall survival (OS) and progression-free survival (PFS) from avelumab maintenance start were 14.9 months (13.1—not estimable [NE) and 6.4 months (4.6—NE), respectively. Enfortumab vedotin (EV) was the most common second-line treatment after avelumab (70%). Median (95% CI) OS and PFS from second-line EV start were 11.6 months (6.1—NE) and 6.6 months (4.1—NE), respectively. Conclusions: Results provide insights into the impact of avelumab first-line maintenance treatment in patients with aUC in the US. Effectiveness data are consistent with previous findings, supporting the use of avelumab maintenance in patients without disease progression following first-line platinum-based chemotherapy. Second-line EV after progression on avelumab maintenance had similar effectiveness to results from other real-world studies. Full article