Search Results (204)

Background/Objectives: Commonly characterized by limited metastatic sites, low tumor burden has been associated with favorable patient outcomes in various malignancies. However, its prognostic relevance in avelumab maintenance therapy for advanced urothelial carcinoma (UC) remains incompletely defined. Methods: We retrospectively analyzed 26 patients with advanced UC who received avelumab maintenance therapy following disease control with first-line platinum-based chemotherapy between March 2021 and May 2025. Patients were categorized by their metastatic pattern at a chemotherapy initiation: lymph node-only (as a surrogate for low tumor burden), non-visceral (excluding visceral organ involvement, but including bone), or visceral disease. Survival outcomes were assessed using the Kaplan–Meier method. Results: Among the cohort, 46.2% had lymph node-only metastasis and 57.7% had non-visceral disease. The median progression-free survival (PFS) and overall survival (OS) from the start of avelumab were 5.6 months and 21.7 months, respectively. OS from the initiation of platinum-based chemotherapy was 28.7 months. Patients with lymph node-only metastasis demonstrated significantly longer OS from chemotherapy initiation compared with those with other metastatic patterns (41.1 vs. 22.9 months, p = 0.044). However, the PFS and OS from avelumab initiation did not significantly differ. No survival benefit was observed for patients with non-visceral disease compared with those with visceral metastases. Conclusions: Lymph node-only metastasis, representing low tumor burden, was associated with significantly improved long-term survival in advanced UC patients undergoing avelumab maintenance following chemotherapy. These findings support the clinical utility of baseline tumor burden and metastatic pattern in risk stratification and shared decision-making for maintenance therapy in advanced UC. Full article

Background and Objectives: Epithelial ovarian cancer (EOC) remains the deadliest gynecologic malignancy, yet the psychosocial dynamics of early survivorship are inadequately described. We prospectively quantified six-month trajectories in the quality of life in a consecutive cohort of 88 women newly diagnosed with EOC and explored clinical moderators of change. Methods: Eighty-eight consecutive patients (mean age 59.1 ± 10.7 years) completed the SF-36, WHOQOL-BREF, EORTC QLQ-C30, and 10-item Perceived Stress Scale (PSS-10) at baseline (pre-therapy) and six months after cytoreductive surgery ± platinum-based chemotherapy. Stage (FIGO I–II vs. III–IV) and treatment pathway (primary debulking surgery, neoadjuvant chemotherapy plus interval debulking, chemotherapy only) data were recorded. Results: Global QoL improved significantly (EORTC Global Health +5.9 ± 7.7 points; p < 0.001) while perceived stress declined (ΔPSS −3.6 ± 5.1; p < 0.001). SF-36 Physical Functioning rose 4.7 ± 7.9 points (p < 0.001) and Mental Health 4.4 ± 7.9 points (p = 0.004). The WHOQOL Physical and Psychological domains gained 4.7 ± 7.1 and 4.3 ± 7.4 points, respectively (both p < 0.01). Advanced-stage patients experienced larger stress reductions than early-stage patients (−4.1 ± 2.7 vs. −2.9 ± 2.2; p = 0.028) but comparable QoL gains. Greater stress relief correlated with greater mental-health improvement (r = −0.51) and global-health gains (r = −0.45) (all p < 0.001). Treatment pathway did not significantly influence trajectories. Conclusions: Early survivorship after first-line ovarian-cancer therapy was characterized by the clinically meaningful recovery of physical and emotional functioning together with the moderate alleviation of perceived stress. Improvements were observed irrespective of stage and treatment strategy, suggesting that contemporary multimodal regimens do not inevitably compromise patient-reported outcomes. Our estimates provide preliminary effect sizes that should be validated in multi-center cohorts with longer follow-up. Full article

Background: In September 2021, pemigatinib received Health Canada approval for previously treated locally advanced/metastatic cholangiocarcinoma (CCA) with FGFR2 rearrangements/fusions. This retrospective study aimed to characterize the real-world management and outcomes of patients with CCA receiving pemigatinib through a Canadian patient support program (PSP). Methods: We evaluated a multi-centre case series of Canadian patients who were prescribed pemigatinib between September 2021 and January 2023 for eligible CCA diagnoses and enrolled in the PSP. The retrospective study data included demographic and disease-, treatment-, and outcome-related information, and these were collected using a survey of prescribing physicians. Results: Of the 26 patients who initiated pemigatinib in the PSP, we received survey responses for 18 (69%). Their median age was 57 years, 67% were female, 61% had stage IV disease, and 83% had intrahepatic CCA. Prior to pemigatinib, a partial hepatectomy was performed in 44% of the patients, and 66% of the patients received 2–4 prior lines of systemic therapy. All patients were treated with platinum-based regimens as the first-line treatment for unresectable/metastatic disease. The median follow-up time on pemigatinib was 12.6 (range: 2.3–28.4) months, and their median real-world progression-free survival (rwPFS) was 12.1 months (95% CI 7.2-NR). The physician-assessed objective response and disease control rates were 56% and 89%, respectively. For the nine patients who discontinued pemigatinib, the median treatment duration was 10.6 months (range: 0.8–21.7). Disease progression was the most common reason for discontinuation (89%). None discontinued due to adverse events. Conclusions: Objective response rates, disease control rates, and a PFS comparable to that in the phase 2 FIGHT-202 trial was reported with pemigatinib use in this Canadian PSP cohort. Full article

Background/Objectives: Response to immune checkpoint inhibitors (ICIs) is associated with several biological pathways, including tumor immunogenicity and antitumor immunity. Identifying host factors involved in these pathways may guide personalized ICI treatment. Methods: We describe the application of chromatin conformation assays to blood from patients with advanced urothelial carcinoma from the phase 3 JAVELIN Bladder 100 trial (NCT02603432). This trial demonstrated a significant survival benefit with avelumab maintenance plus best supportive care (BSC) vs. BSC alone following non-progression with platinum-based chemotherapy as first-line therapy. Blood-based chromatin conformation markers (CCMs) were screened for associations with high/low immune effector gene expression in tumors and for interactions with outcomes and tumor mutation burden. Results: Candidate CCMs included genes involved in several immune response pathways, such as POU2F2, which encodes a transcription factor that regulates B-cell maturation. Conclusions: Our findings suggest that polygenic host factors may affect response to ICIs and support further investigation of chromatin conformation assays. Full article

Small-cell lung cancer (SCLC) is an aggressive malignancy with poor prognosis despite initial responsiveness to chemotherapy. Platinum-based chemotherapy with etoposide has long been the standard first-line treatment, but recent advances in immunotherapy have improved outcomes. Phase III trials, including IMpower133 and CASPIAN, demonstrated that adding immune checkpoint inhibitors, such as atezolizumab and durvalumab, to chemotherapy significantly enhances overall survival (OS) and progression-free survival (PFS). This case report describes a 76-year-old former smoker diagnosed with extensive-stage SCLC (ES-SCLC) following the detection of a left lower lung mass. The patient underwent combination therapy with carboplatin, etoposide, and atezolizumab, followed by maintenance atezolizumab. The patient demonstrated a sustained response to treatment, with significant tumor regression and no evidence of disease progression. Despite advanced age and comorbidities, treatment was well-tolerated, with no severe adverse events. Serial imaging over 24 months confirmed sustained disease stability, with regression of mediastinal lymphadenopathy and no new lesions. This case highlights the potential for prolonged disease control in select SCLC patients treated with chemo-immunotherapy. The absence of significant toxicities underscores the feasibility of immunotherapy even in elderly patients with comorbidities. These findings support the role of atezolizumab as a key component of ES-SCLC treatment and suggest the need for further research on predictors of durable response. Full article

This retrospective cohort study evaluated characteristics, treatment patterns, and clinical outcomes in adults with locally advanced/metastatic urothelial carcinoma (la/mUC) receiving first-line (1L) systemic treatment with or without avelumab 1L maintenance (1LM) between January 2020 and July 2023. The index date was the first date with a claim for 1L systemic therapy after a la/mUC diagnosis. Patients with continuous health plan enrollment for ≥6 months before and ≥1 month after the index date were identified from Carelon Research’s Healthcare Integrated Research Database. Of 2820 patients receiving 1L treatment, 37.0% received platinum-based chemotherapy (PBC); 39.0%, immuno-oncology (IO) monotherapy; and 24.0%, other therapies. Renal disease and other comorbidities influenced 1L regimen choice. Healthcare resource utilization (HCRU) and costs were reported for patients receiving second-line (2L) treatment. HCRU was high in 32.8% of patients (926 of 2820) who received 2L treatment. Median all-cause direct medical costs per patient per month were USD 15,859, USD 19,781, USD 11,346, and USD 9516 for 1L PBC, 1L PBC + avelumab 1LM, 1L IO monotherapy, and 1L other therapies, respectively. Most direct healthcare costs were attributed to all-cause outpatient visits. Full article

Pleural malignancies represent a clinically devastating group of oncological disorders, most commonly arising from metastatic disease, with lung and breast cancers being the most frequent primary sites. Malignant pleural mesothelioma is a primary malignancy of the pleura and occurs less often than metastatic pleural disease. Pleural malignancies often present with malignant pleural effusion, which typically indicates advanced-stage disease and is associated with poor overall prognosis. Treatment of pleural malignancies includes both palliative and definitive approaches. Palliative interventions primarily aim to relieve symptoms and improve quality of life. Definitive treatments include systemic chemotherapy, targeted therapy, and immunotherapy, depending on the type and molecular profile of the underlying tumor. In mesothelioma, platinum-based chemotherapy in combination with pemetrexed remains the cornerstone of treatment, while the combination of nivolumab and ipilimumab is recommended as first-line therapy for unresectable disease. For metastatic disease, systemic therapy is typically tailored to the primary tumor’s characteristics. Intrapleural administration of chemotherapeutic agents is one of the therapeutic strategies and hyperthermic intrathoracic chemotherapy and pressurized intrathoracic aerosol chemotherapy are the most recent innovations that are under active investigation. This review provides an up-to-date synthesis of systemic chemotherapy strategies for pleural malignancies, their integration with targeted and immune-based therapies, and recent advances in intrapleural chemotherapy modalities. It also explores existing knowledge gaps and outlines directions for future research and potential changes in clinical practice. Full article

Background/Objectives: To summarize the relevant trials relating to novel strategies and therapeutic advances in the treatment of bladder cancer. Methods: A comprehensive review of the literature and recent/ongoing clinical trials was conducted, focusing on novel treatments and strategies for bladder cancer. Trials started or published as of 2020 were included. Results: The standard of care for MIBC remains neoadjuvant chemotherapy with perioperative immunotherapy in the cisplatin-eligible population, while guidelines do not exist for cisplatin-ineligible patients. Strategies under investigation include combinations of chemotherapy, immunotherapy, radiation, and/or novel therapies, such as ADCs, targeted agents, intravesical treatments, and personalized vaccines. Bladder-sparing approaches using these novel therapies are also being studied. In the advanced/metastatic setting, enfortumab vedotin plus pembrolizumab has supplanted platinum-based chemotherapy as the first-line treatment option. For those with contraindications, or who progress, strategies under investigation include newer immunotherapies and ADCs, novel small molecule inhibitors, and cellular therapies. Conclusions: The treatment landscape for bladder cancer has changed drastically within the last few years. Ongoing trials hope to build on this success by investigating bladder-sparing strategies for MIBC and novel systemic therapies in advanced patients. Full article

Ovarian cancer is the most lethal gynecological cancer. Up to 75% of cases are high-grade serous ovarian cancer (HGSOC) that have high chemosensitivity to first-line platinum-based therapies. However, 75% of patients will become chemoresistant following relapse. The underlying mechanism for developing resistance to chemotherapy in HGSOC is poorly understood. In this study, we employed Matrix-Assisted Laser Desorption/Ionization–Mass Spectrometry Imaging (MALDI-MSI) on matching formalin-fixed paraffin-embedded (FFPE) HGSOC tissues at the time of diagnosis and following relapse with chemotherapy-resistant disease (n = 4). We identified m/z values that were differentially abundant in the matching diagnosis and relapse HGSOC tissues. These were matched to proteins using nano-liquid chromatography tandem mass spectrometry (LC-MS/MS). We identified upregulated proteins in the HGSOC relapse tissues, including COL12A1, FUBP1, PLEC, SLC4A1, and TKT. These proteins were validated by immunohistochemistry (IHC) and gene expression using online databases. IHC showed COL12A1, FUBP1, PLEC, SLC4A1, and TKT protein abundance were significantly elevated in HGSOC relapse tissues compared to matching tissues at diagnosis. COL12A1, FUBP1, PLEC, and TKT mRNA expression levels were significantly increased in HGSOC compared to normal ovary and associated with poor prognosis in HGSOC. We confirmed that higher protein abundance of both COL12A1 and PLEC correlated with reduced progression-free survival in HGSOC patients. Furthermore, both COL12A1 and PLEC mRNA and protein levels were significantly associated with chemotherapy resistance. In summary, using MALDI-MSI, we have identified proteins, including COL12A1 and PLEC, associated with chemotherapy resistance to be further evaluated as HGSOC biomarkers and/or therapeutic targets. Full article

Background and Objectives: Despite developments in cervical cancer (CC) treatment, an advanced stage is a poor prognostic factor. Cervical cancer is an immunogenic tumor in which viruses, like HPV, play a role in carcinogenesis. Therefore, systemic inflammatory markers (SIMs) may have prognostic value. Most studies on SIMs focus on the early stage by evaluating pretreatment levels. This study aims to evaluate the prognostic and predictive values of both pretreatment and post-treatment parameters at the advanced stage, as well as treatment efficacy after progression with first-line treatment. Materials and Methods: A total of 133 advanced-stage CC patients with progression on first-line platin–paclitaxel and bevacizumab were evaluated retrospectively. Demographic and histopathological characteristics were recorded along with treatment details. Pre-treatment baseline blood parameters and post-treatment follow-up values were recorded to calculate SIMs as the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), systemic immune-inflammation index (SII), and systemic inflammatory response index (SIRI). Results: Median values for SIMs were accepted as cut-off values. Post-treatment values demonstrated stronger predictive power, with pre-treatment SIRI and NLR being significant only in univariate analysis, but not in multivariate analysis. High post-treatment SIRI (>2.1) was correlated with shorter overall survival (OS) and considered a poor prognostic factor. High post-treatment SIRI (>2.1), -SII (>746), and -PLR (>197) emerged as independent prognostic factors for progression-free survival (PFS). Their prognostic values were clearer in the whole population and the metachronous metastatic subgroup. Rechallenge of platinum-based chemotherapy was an option for those who had at least 6 months of PFS with first-line platinum-based chemotherapy. Bevacizumab addition to single-agent or combination regimens led to improved ORR as well. Conclusions: Post-treatment SIRI is a promising prognostic factor for OS, while post-treatment SIRI, SII, and PLR may serve as convenient SIMs for PFS. Platinum-based combination chemotherapy reinduction is a feasible second-line treatment strategy, especially with the addition of bevacizumab. Full article

Backgroud: Ovarian cancer is the deadliest gynecologic malignancy, with most patients presenting with peritoneal dissemination at diagnosis. Complete cytoreduction and sensitivity to platinum-based systemic chemotherapy remain the most significant prognostic factors. However, even after optimal first-line management, over half of patients relapse due to residual microscopic disease. Intraperitoneal chemotherapy aims to target this component, with normothermic intraperitoneal chemotherapy long-term (NIPEC-LT) and hyperthermic intraperitoneal chemotherapy (HIPEC) being the most studied approaches. While NIPEC-LT has demonstrated improved survival in select trials, concerns regarding toxicity and catheter-related complications have limited its adoption as standard care. Conversely, HIPEC has shown survival benefits, particularly in patients undergoing interval cytoreductive surgery (iCRS) after neoadjuvant chemotherapy, leading to its inclusion in clinical guidelines. However, HIPEC is administered as a single intraoperative treatment, limiting its prolonged effect. Objectives and Method: This study investigates the combination of HIPEC and postoperative NIPEC-LT in the BICOV-1 trial, a prospective, non-randomized phase I study evaluating the feasibility, safety, and oncologic outcomes. The primary objective is to assess the treatment completion rates and morbidity. The secondary endpoints include disease-free survival (DFS), overall survival (OS), and quality-of-life measures. Combining HIPEC and NIPEC-LT is a rational approach, as both have shown independent benefits and do not overlap in toxicity. HIPEC-induced biological changes may enhance the effectiveness of subsequent intraperitoneal chemotherapy. This trial will provide essential data for future phase II/III studies assessing the role of intensified intraperitoneal treatment in ovarian cancer management. Full article

Background/Objectives: The Lung Immune Prognostic Index (LIPI) has emerged as a promising biomarker for predicting outcomes in advanced non-small cell lung cancer (aNSCLC). We assessed whether LIPI, in combination with baseline clinical characteristics, can guide first-line treatment selection between pembrolizumab (P) and pembrolizumab plus platinum-based chemotherapy (PCT) in patients with PD-L1 tumor proportion score (TPS) ≥ 50% and EGFR/ALK/ROS1 wild-type. Methods: A predictive score was developed using baseline clinical variables, including age, sex, smoking status, and LIPI, in a proof-of-concept cohort (n = 241). This model was then validated in an independent cohort of 409 patients. OS was compared between patients treated with P versus PCT, stratified by predictive score. Results: In the proof-of-concept cohort, the median OS was 18.3 months for P and 26.6 months for PCT (p = 0.001). In the validation cohort, the median OS was 28.0 months for P and 22.2 months for PCT (p = 0.062). Stratification using the predictive score showed that patients with high scores (3–5) had improved OS with PCT compared to P (31.2 vs. 25.5 months, p = 0.001), while those with low scores (0–2) derived similar benefits from both treatments. Conclusions: This LIPI-based predictive score may assist in identifying aNSCLC patients who derive greater benefit from chemo-immunotherapy over immunotherapy. Its simplicity and clinical relevance support integration into treatment decision-making, pending prospective validation. Full article

The cornerstone of first-line treatment in extensive-stage small cell lung cancer (ES-SCLC) is platinum- and etoposide-based chemotherapy. Platinum compounds could immunomodulate the tumor microenvironment in addition to their cytotoxic effect. Genetic variation in immune checkpoint (IC) pathways may predict chemotherapy efficacy. Polymorphisms in the IC genes were determined, and their association with survival was analyzed in 78 patients with ES-SCLC treated with chemotherapy. PD-L1 protein expression in tumor tissue was determined. Three variants in CD274 were associated with better median progression-free survival (mPFS): rs2297136 (hazard ratio [HR] 0.52, 95% CI 0.29–0.93; p = 0.03), rs2282055 (HR 0.23, 95% CI 0.09–0.64; p = 0.005), and rs822336 (HR 0.41, 95% CI 0.23–0.73; p = 0.002). CTLA4 rs231775 was also associated with mPFS (HR 0.30, 95% CI 0.14–0.63; p = 0.002). The variants CD274 rs2297136 and CD274 rs822336 were associated with platinum sensitivity (odds ratio [OR] 0.13, 95% CI 0.02–0.70; p = 0.02, and OR 0.08, 95% CI 0.01–0.46; p = 0.005, respectively). CD274 rs2297136 was also associated with better overall survival (p = 0.02), but not after adjustment for covariates. No association was found between CD274 germline variants and PD-L1 tumor expression. Our results suggest that CD274 and CTLA4 variants may be predictive biomarkers for platinum plus etoposide treatment in ES-SCLC. Full article

 Background/Objectives: Extrapulmonary neuroendocrine carcinomas (EP-NECs) are rare, aggressive malignancies with no standardized treatment approach. Although platinum-based chemotherapy is considered the first-line therapy, overall survival (OS) and progression-free survival (PFS) remain limited. This study aims to evaluate the clinical and pathological characteristics of EP-NEC patients, their treatment responses, and survival outcomes. Methods: This retrospective observational study included 29 EP-NEC patients diagnosed and followed between 2015 and 2024. Clinical and demographic data, tumor localization, disease stage, administered treatments, and survival outcomes were analyzed. Kaplan–Meier survival analysis was used to assess OS and PFS, with subgroup comparisons performed via the log-rank test. Results: The most common primary tumor sites were the pancreas (21%), prostate (17%), and cervix (14%). At diagnosis, 55.2% of patients had metastatic disease. First-line platinum-based chemotherapy achieved an objective response rate of 82.1%, with a median PFS of 8.16 months and a median OS of 14.16 months. Surgical intervention significantly improved survival (p = 0.020), while a high Ki-67 proliferation index (>80%) was associated with worse PFS (p = 0.032). Other factors, including smoking status and liver-directed therapies, had no significant impact on survival. Conclusions: EP-NECs present with a poor prognosis despite platinum-based chemotherapy achieving high response rates. Surgical resection improves survival outcomes, whereas high Ki-67 expression is associated with a worse prognosis. These findings highlight the need for further research into novel therapeutic strategies for EP-NECs. Full article

Avelumab first-line maintenance (1LM) is approved for patients with locally advanced or metastatic urothelial carcinoma (la/mUC) who do not have disease progression after platinum-based chemotherapy (PBC). This retrospective study describes real-world treatment patterns and clinical outcomes in patients with la/mUC who initiated first-line (1L) systemic treatments, including avelumab 1LM, within iKnowMed, the US community oncology electronic health records database, between 1 December 2019 and 30 November 2023 and followed through 28 February 2024. In total, 1658 patients with la/mUC initiated 1L treatment: immuno-oncology (IO) monotherapy (41.2%), PBC only (32.4%), PBC followed by avelumab 1LM (11.2%), and other treatments (15.1%). The median OS (95% CI) from the start of 1L treatment was 20.4 (13.8, 30.0), 11.0 (8.5, 14.5), and 14.6 (12.6, 17.3) months for cisplatin-based only, carboplatin-based only, and IO monotherapy, respectively. Among the overall population, 36.1% and 11.8% of patients received second-line (2L) and third-line treatment, respectively. The median (95% CI) OS from the start of avelumab 1LM was 18.5 (13.8, 23.8) months. After discontinuation of avelumab 1LM, 43.5% received 2L treatment, and 59.3% of those received enfortumab vedotin (EV); the median (95% CI) OS from start of 2L EV was 12.7 (7.2, 16.5) months. Survival outcomes among patients treated with avelumab 1LM and 2L EV are consistent with respective clinical trials and other real-world studies. Full article