BACKGROUND:Enfortumab vedotin plus pembrolizumab (EV + P) is an established standard of care for metastatic urothelial carcinoma; however, real-world data remain limited. We evaluated clinical outcomes in patients treated in the frontline metastatic setting. PATIENTS AND METHODS:The primary endpoint was objective response rate (ORR); secondary endpoints included overall survival (OS), progression-free survival (PFS), duration of response, and safety. Median follow-up and survival outcomes were estimated using reverse and standard Kaplan-Meier methods and Cox regression analyses. RESULT:Overall, 160 patients were included, with 148 (92.5%) receiving EV + P in the 1L. The median follow-up was 14 months. In the 1L, the median PFS was 12 months (95% CI, 6.4-17.6). The CR rate was 14.9% and the PR rate was 54.1%, resulting in an ORR of 69.0%. SD and PD were observed in 16.9% and 14.1% of patients, respectively. Among patients achieving CR or PR, the median duration of response was 20 months (95% CI, 11.3-28.6). In univariate analyses for PFS, patients with upper urinary tract tumors had significantly shorter PFS compared with those with lower urinary tract tumors (5 vs. 20 months, P = .004). Patients with ECOG PS ≥ 2 had shorter PFS than those with ECOG PS ≤ 1 (3 vs. 16 months; P = .002). De novo metastatic disease was associated with worse PFS (6 vs. 23 months, P = .07). In the 1L EV + P cohort, 12- and 24-month OS rates were 73.8% and 57.7%, respectively. In the ≥ 2-line cohort (n = 12), the ORR was 66.7%, with PR in 58.4% and CR in 8.3%; SD and PD were observed in 8.3% and 25.0% of patients, respectively. Overall, 80.6% of patients experienced at ≥ 1 treatment-related adverse event (TRAEs) of any grade, and 19 patients (13.7%) developed grade 3 to 4 TRAEs. CONCLUSIONS:In this real-world cohort, EV + P demonstrated meaningful clinical activity and manageable safety as frontline therapy, consistent with EV-302.

BACKGROUND:In the present study, we evaluated pretreatment prognostic factors for overall survival in patients with metastatic urothelial carcinoma who received maintenance avelumab within the Expanded-Access Program. PATIENTS AND METHODS:We retrospectively analyzed 132 patients with metastatic urothelial carcinoma who received at least one cycle of avelumab. Overall survival (OS) was estimated using the Kaplan-Meier method. Univariate analysis was performed to identify pretreatment prognostic factors associated with OS (p < 0.05), and significant variables were included in a multivariate Cox model. RESULTS:Median age was 67 years (range, 43-84) and the bladder was the primary tumor site in 78% of patients. Visceral metastases were present in 62.5% of patients, and 32% had lymph node-only disease. ECOG ≥ 1 was observed in 59.1%, and 57% received cisplatin-based chemotherapy. The median follow-up was 24 months, the median OS was 23.8 months, and the 24-month OS rate was 47% (95% CI, 35%-55%).In univariate analysis, liver metastases, bone metastases, and hemoglobin < 10 g/dL were significantly associated with OS. In multivariate analysis, bone metastases (HR = 2.3; 95% CI 1.3-5; p = 0.008) and hemoglobin < 10 g/dL (HR = 2.6; 95% CI 1.2-4.1; p = 0.004) remained independent predictors of worse OS. CONCLUSIONS:Bone metastases and low hemoglobin are independent predictors of poor survival in patients receiving maintenance avelumab, supporting their role in risk stratification.

e23009 Background: Screen failure and treatment dropout remain major barriers to successful conduct of oncology clinical trials, particularly in real-world, middle-income settings. Data evaluating both patient- and center-related factors influencing screen failure, dropout, and time to dropout are limited. Methods: This multicenter retrospective analysis included 1,229 oncology patients screened for clinical trials across 13 centers in Türkiye. Causes of screen failure and dropout were descriptively analyzed. Time to dropout was assessed using median values and compared across subgroups using the Mann–Whitney U and Kruskal–Wallis tests. Results: Overall, 1,155 patients experienced screen failure, and 74 patients dropped out after trial initiation. Patients with screen failure had a median age of 64 years, and 67.3% were male. The most frequent cancer types among screen failure patients were lung (57.0%), breast (13.7%), and prostate cancer (8.6%). The primary causes of screen failure in the overall cohort were non-fulfillment of inclusion criteria (69.4%), presence of exclusion criteria (21.4%), and patient non-compliance (4.1%). Among the 74 patients who dropped out, 63.5% were male, with a median age of 62 years; the most common diagnoses were lung (44.6%), gastric (27.0%), and breast cancer (23.0%). The leading causes of dropout were adverse events (33.8%), disease progression (28.4%), and patient dissatisfaction (14.9%). Median time (months) to dropout was significantly shorter in female patients (3 vs 7, p = 0.014), patients without comorbidities (7 vs 8, p = 0.036), those treated in neoadjuvant or adjuvant compared with metastatic settings (7.5 vs 6.5 vs 8, p < 0.001), patients receiving parenteral compared with oral or oral plus parenteral regimens (7 vs 9.5 vs 13, p = 0.035), and in centers with a clinical research unit or a clinical research center compared with centers without an administratively organized unit (7 vs 6.5 vs 10, p = 0.010). Finally, time to dropout decreased with increasing sub-investigator research experience, defined as the total number of clinical trials in which the sub-investigator had previously participated (0–5, 6–10 and > 10 trials, respectively; median 9.5 vs 7 vs 5 months; p = 0.022). Principal investigator experience and total trial volume per center were not associated with time to dropout. Conclusions: In this multicenter study, screen failure in clinical trials was predominantly driven by eligibility criteria, while treatment dropout was mainly related to toxicity and disease progression. Time to dropout varied according to patient characteristics, treatment setting, route of administration, and center-level factors, underscoring the influence of both clinical and operational elements on trial retention. These findings highlight the importance of pragmatic trial design and strengthened research infrastructure to improve feasibility and retention.

BACKGROUND:Epithelial ovarian cancer frequently recurs and becomes resistant to platinum chemotherapy. We investigated whether adding pembrolizumab to weekly paclitaxel, with or without bevacizumab, improves progression-free survival and overall survival compared with weekly paclitaxel, with or without bevacizumab, in participants with platinum-resistant recurrent ovarian cancer who had received one to two previous systemic regimens. METHODS:ENGOT-ov65/KEYNOTE-B96 is a randomised, double-blind, phase 3 study conducted at 187 gynaecologic oncology centres in 25 countries in the Americas, Asia, Europe, and Oceania. Adults (≥18 years) with histologically confirmed epithelial ovarian, fallopian tube, or primary peritoneal carcinoma, who received one to two previous systemic therapies including at least one platinum regimen and who progressed 6 months or less after the last platinum regimen, were eligible. Participants were randomly assigned 1:1 to intravenous pembrolizumab 400 mg every 6 weeks for up to 18 cycles plus open-label intravenous paclitaxel 80 mg/m2 on days 1, 8, and 15 of each 21-day cycle or intravenous placebo (saline solution) every 6 weeks for up to 18 cycles plus open-label intravenous paclitaxel 80 mg/m2 on days 1, 8, and 15 of each 21-day cycle; intravenous bevacizumab 10 mg/kg every 2 weeks was permitted per investigator. Randomisation was stratified by planned bevacizumab use, region, and PD-L1 combined positive score (CPS). The primary endpoint was investigator-assessed progression-free survival per RECIST version 1.1; the key secondary endpoint was overall survival. Results from two interim analyses and the final analysis are included in this Article. This study is registered with ClinicalTrials.gov, NCT05116189, and is now completed. FINDINGS:Between Dec 13, 2021, and July 3, 2023, 643 female participants were randomly assigned; 322 to pembrolizumab plus paclitaxel and 321 to placebo plus paclitaxel. At the first interim analysis, pembrolizumab plus paclitaxel significantly improved progression-free survival versus placebo plus paclitaxel in both the PD-L1 CPS 1 or higher (median 8·3 months vs 7·2 months; hazard ratio [HR] 0·72; 95% CI 0·58-0·89; p=0·0014 α=0·012]) and overall populations (median 8·3 months vs 6·4 months; HR 0·70, 95% CI 0·58-0·84; p<0·0001, [α=0·0023]), meeting the prespecified criteria for confirmatory efficacy. At the second interim analysis, overall survival was significantly improved in the PD-L1 CPS 1 or higher population (median 18·2 months vs 14·0 months; HR 0·76, 95% CI 0·61-0·94; p=0·0053, [α=0·0083]). At the final analysis, overall survival was significantly improved in the overall population (median 17·7 months vs 14·0 months; HR 0·82, 95% CI 0·69-0·97; p=0·011 [α=0·024]). Grade 3 or worse treatment-related adverse events occurred in 217 (68%) of 320 participants in the pembrolizumab plus paclitaxel group versus 176 (55%) of 318 participants in the placebo plus paclitaxel group. The most common treatment-related adverse events (any grade) included anaemia, peripheral neuropathy, alopecia, fatigue, and nausea. Treatment-related adverse events resulted in death in four participants (1%) in the pembrolizumab plus paclitaxel group (colitis, interstitial lung disease, acute myeloid leukaemia, and intestinal perforation) and in five participants (2%) in the placebo plus paclitaxel group (cardiac failure, intestinal perforation [in two participants], and large-intestine perforation [in two participants]). INTERPRETATION:Pembrolizumab plus weekly paclitaxel, with or without bevacizumab, significantly improved progression-free survival and overall survival in participants with platinum-resistant recurrent ovarian cancer who had received one to two previous systemic regimens, supporting this regimen as a new treatment option for this population. FUNDING:Funded by Merck Sharp & Dohme LLC, a subsidiary of Merck & Co, Inc, Rahway, NJ, USA.

Background: Poly(ADP-ribose) polymerase (PARP) inhibitors have been established as a first-line maintenance therapy in advanced epithelial ovarian cancer (EOC) following platinum-based chemotherapy. While phase III trials have demonstrated significant progression-free survival (PFS) benefits with olaparib and niraparib, real-world data remain limited. Methods: This retrospective, multicenter real-world study included 179 patients with newly diagnosed epithelial ovarian treated with first-line maintenance olaparib or niraparib across 33 centers in Türkiye between January 2014 and March 2025. Clinical, pathological, and molecular data-including BRCA (Breast Cancer Susceptibility Gene) mutation status, origin, and variant classification-was collected. The primary endpoint was PFS, and secondary endpoints included overall survival (OS) and safety. Survival outcomes were analyzed using Kaplan-Meier methods. Results: Of 179 patients, 110 received olaparib and 69 received niraparib. BRCA mutations were present in 88.3% of patients, while 11.7% had unknown HRD status. Median follow-up was 16.5 months, and median PFS was not reached. Estimated PFS rates for the overall cohort were 91.0% at 6 months, 83.0% at 12 months, and 64.0% at 24 months. In the olaparib cohort, BRCA-mutant patients demonstrated PFS rates of 89%, 78%, 73%, and 64% at 6, 12, 18, and 24 months, respectively. In the niraparib cohort, corresponding PFS rates among BRCA-mutant patients were 87% at 6 months and 75% at 12 months. Patients harboring pathogenic BRCA variants experienced longer PFS compared with those with likely pathogenic variants. Any-grade adverse events occurred in 73.7% of patients, and grade 3-4 events in 29.6%, with hematologic toxicities predominating. Dose interruptions were more frequent with niraparib, while treatment discontinuation rates were low in both groups. No cases of myelodysplastic syndrome or acute myeloid leukemia were observed. Conclusions: In this large multicenter real-world cohort, first-line maintenance therapy with olaparib and niraparib provided durable PFS benefit in patients with advanced EOC, particularly among those with pathogenic BRCA mutations, confirming their effectiveness and manageable safety profiles in routine clinical practice.

The recommended adjuvant chemotherapy (adj-ChT) regimen for resected biliary tract cancers (BTC) is capecitabine (Cape); yet, the recommendation is based on limited evidence. Although varied adj-ChTs have been employed in practice, robust real-world data is scarce. We conducted a national, multicenter, hospital-based registry study to evaluate adj-ChTs in resected BTCs. Patients who received adj-ChT (± radiotherapy) between 2010 and 2024 were included. Recurrence-free (RFS) and overall survival (OS) were analyzed by adjusted Cox-regression and propensity score-based inverse-probability-of-treatment-weighting (IPTW), addressing selection bias. Among 617 patients from 44 centers, 513 were eligible. The most frequent adj-ChTs were Cape (35.5% [n = 182]), gemcitabine-cisplatin (Gem-Cis; 22.4% [n = 115]), gemcitabine-capecitabine (Gem-Cape; 20.1% [n = 103]), and gemcitabine (Gem; 10.7% [n = 55]). Median RFS and OS with Cape were 19.7 (95% Confidence Interval [95% CI]: 14.2-41.1) and 41.9 months (95% CI: 25.9-69.2). In adjusted/controlled comparisons with Cape, no differences in RFS or OS were observed with Gem-Cis (RFS: Hazard Ratio [HR] 1.13 [95% CI: 0.77-1.66]; OS: HR: 1.03 [95% CI: 0.66-1.61]), Gem-Cape (RFS: HR 0.97 [95% CI: 0.68-1.38]; OS: HR: 0.81 [95% CI: 0.52-1.24]), or Gem (RFS: HR 1.00 [95% CI: 0.63-1.59]; OS: HR: 0.93 [95% CI: 0.55-1.57]). Similarly, IPTW analyses showed no difference in RFS and OS. Radiotherapy appeared to be associated with improved survival. Performance status, T-stage, lymph-node positivity, and R1-resection were independently associated with RFS and OS. In conclusion, this real-world study did not identify a regimen superior to Cape. Given the modest benefit of adj-ChTs, novel approaches, including neoadjuvant and targeted/immunotherapy strategies, are needed.

BRCA1/2 germline pathogenic variants confer markedly elevated lifetime risks for breast, ovarian, prostate, and pancreatic cancers. Preimplantation genetic testing for monogenic disorders (PGT-M) is an embryo-selection step performed within an in vitro fertilization (IVF) cycle that enables carriers to select embryos unaffected by the familial pathogenic variant, substantially reducing-though not eliminating-the risk of transmission. Despite regulatory approval by ESHRE since 2003 and accumulating evidence of clinical and cost-effectiveness, PGT-M remains systematically underutilized in Türkiye. This study aimed to simultaneously assess PGT-M knowledge and attitudes among physicians managing BRCA-positive individuals and among patients and carriers themselves, to quantify the knowledge-action gap, and to characterize PGT counseling practices. A cross-sectional dual-survey study was conducted including 206 physicians and 72 BRCA1/2-positive individuals. Descriptive statistics and subgroup comparisons were performed. Binary logistic regression identified factors associated with adequate physician knowledge. Only 33.0% of physicians reported adequate perceived knowledge, whereas 80.1% considered it medically appropriate and 71.8% would recommend it, demonstrating a marked knowledge-attitude paradox. Excluding genetics and gynecology specialists, adequate perceived knowledge dropped to 16.2%. Among patients, 69.4% had never received PGT information during counseling, and only 16.7% would consider PGT. Younger patients (< 40 years) showed numerically higher receptivity (28.6% vs. 11.8% in those aged ≥ 40 years), although this difference was not statistically significant. In Turkish BRCA clinical practice, positive attitudes toward PGT coexist with substantial knowledge deficits. Patients under 40, who carry the greatest reproductive urgency and highest potential benefit from PGT, are more receptive but remain inadequately counseled. Integrating PGT into routine genetic counseling protocols, implementing specialty-targeted continuing medical education focusing on medical oncology and surgery, and establishing national oncofertility coordination may represent important strategies toward closing this gap.

PURPOSEEarly-onset gastrointestinal cancers are concerning entities globally, yet early-onset biliary tract cancers (EOBTCs) are understudied. Early-stage disease is crucial for young patients' survival.METHODSTOG/GI-SAFRADJU (ClinicalTrials.gov identifier: NCT06975917) is a multicenter, hospital-based, registry initiative of the Turkish Oncology Group, including patients with resected BTCs. Early-onset was defined as a diagnosis at age <50 years. Characteristics and survival of EOBTC and non-EOBTC were compared. Among patients with EOBTC, prognostic factors for recurrence-free survival (RFS) and overall survival (OS) were analyzed. Risk scores were assigned on the basis of hazard ratios.RESULTSSix hundred seventeen patients from 44 centers were included. 12.6% (n = 78) were EOBTC. R1 resection rate was significantly higher among EOBTC (37.1% v 25.7%, P = .038). Adjuvant treatments did not differ between EOBTC and non-EOBTC. Among patients who received adjuvant chemotherapy, RFS (13.9 months [95% CI, 11.4 to 22.1] v 15.9 months [95% CI, 13.6 to 18.9], P = .947) and OS (35.6 months [95% CI, 28.0 to 81.4] v 31.3 months [95% CI, 27.8 to 44.3], P = .670) were similar between EOBTC and non-EOBTC groups. Among patients with EOBTC, R1-resection and high CA19-9 levels were associated with shorter RFS, and gallbladder localization and high CA19-9 were associated with shorter OS in adjusted analyses. Using these factors, risk scores early-stage EOBTC RFS score (EOB-RS) for RFS and early-stage EOBTC OS score (EOB-OS) for OS were formed, each including three ranks. Both scores significantly ordered the prognosis of patients with EOBTC (EOB-RS, [0 points]: 22.7 months, [1 or 2]: 10.3 months, [3]: 5.7 months, P < .001, EOB-OS: [0]: 110.9 months, [1 or 2]: 29.6 months, [3]: 10.1 months, P < .001).CONCLUSIONResected EOBTC patients showed survival comparable to older counterparts receiving surgery/adjuvant therapy. This study suggests a potential risk scoring system for early-stage EOBTC, pending validation.

Pembrolizumab has shown manageable safety and modest antitumor activity when used as a single agent in participants with metastatic castration-resistant prostate cancer (mCRPC). Preclinical evidence suggests that lenvatinib, a vascular endothelial growth factor-targeted agent, inhibits angiogenesis and cell migration in prostate cancer. Safety and efficacy of pembrolizumab plus lenvatinib in participants with docetaxel-pretreated mCRPC were evaluated in cohort E of the phase 1b/2 KEYNOTE-365 study. Eligible adults with confirmed mCRPC, Eastern Cooperative Oncology Group performance status (ECOG PS) scores of 0 or 1, and prior docetaxel treatment for mCRPC received pembrolizumab 200 mg intravenously every 3 wk, for ≤35 cycles, plus oral lenvatinib 20 mg daily, continuously from day 1 of cycle 1, unless specific discontinuation criteria were met. Primary endpoints were prostate-specific antigen (PSA) response rate; objective response rate (ORR), per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST) v1.1, by blinded independent central review; and safety. A total of 39 participants received treatment, with a median follow-up of 9.7 mo (interquartile range, 8.5-11.3). Confirmed PSA response rate was 34% (95% confidence interval [CI], 20-51). ORR for participants with RECIST-measurable disease was 36% (95% CI, 18-57). Treatment-related adverse events (AEs) of any grade occurred in 92% of participants and grade 3-5 treatment-related AEs occurred in 62% of participants. Two participants died of non-treatment-related AEs (acute kidney injury and unspecified death). Clinical trial registry: NCT02861573.

4627 Background: IMvigor011 (NCT04660344) showed that serial ctDNA-based molecular residual disease (MRD) monitoring can identify patients (pts) with MIBC at very high risk of recurrence who benefit from adjuvant atezolizumab (atezo), demonstrating statistically significant and clinically meaningful improvements in DFS and OS vs placebo (pbo) in pts who tested ctDNA+. Pts who persistently tested ctDNA− had low risk of recurrence or death without adjuvant treatment (tx; Powles NEJM 2025). Here we report pt-reported outcomes (PROs). Methods: Pts with MIBC and no radiographic disease were enrolled and underwent serial ctDNA monitoring for up to 1 year after cystectomy; pts who tested ctDNA+ and remained disease-free were randomized to atezo or pbo every 4 weeks (wk) for 12 cycles or up to 1 year. PROs were assessed on Day (D)1 of Cycle (C)1, C3, C5, C7, C9, and C11, and at tx discontinuation. Time to confirmed deterioration (TTCD) analysis of physical functioning (PF), role functioning (RF), and global health status/quality of life (GHS/QoL) were secondary endpoints. Symptoms, functioning, and GHS/QoL per EORTC QLQ-C30, and tx side-effect burden per EORTC IL46, were exploratory endpoints. Relevant adverse events (AEs) were graded per NCI CTCAE v5. Results: Eligible pts who tested ctDNA+ (n=250) were randomized to atezo (n=167) or pbo (n=83). QLQ-C30 completion was >94% at C1D1 and >87% during tx, and >72% and >90%, respectively, for IL46. C1D1 completion rates were similar between arms. TTCD in PF, RF, and GHS/QoL showed no evidence of a difference between arms (Table). There was no clinically meaningful difference in mean change from C1D1 in symptoms, functioning, and GHS/QoL over time through C11D1 and between arms. From C1D1 to C11D1, >90% of pts reported little or no tx side-effect burden in both arms. Relevant safety data showed consistency between AEs and PROs. Conclusions: ctDNA-guided adjuvant atezo provided clinically meaningful DFS and OS benefit without negatively impacting pt-reported QoL. Clinical trial information: NCT04660344 . Atezo(n=167) Pbo(n=83) Stratified HR a (95% CI) QLQ-C30, median TTCD b (95% CI), mo PF 25.1 (18.5, NE) NE (19.4, NE) 1.25 (0.76, 2.07) RF 18.5 (12.2, NE) NE (19.4, NE) 1.45 (0.88, 2.40) GHS/QoL 35.4 (19.3, NE) 16.5 (10.9, NE) 0.71 (0.45, 1.12) IL46 tx side-effect burden, % of pts Atezo C1D1 (n=131) Atezo C11D1 (n=60) Pbo C1D1 (n=60) Pbo C11D1 (n=22) Not at all/a little 93.9 98.3 98.3 95.5 Quite a bit 6.1 1.7 1.7 4.5 Very much 0 0 0 0 a Stratification factors: Nodal status (+ vs –); tumor stage (≤pT2 vs pT3/4); programmed death ligand-1 status (<5% vs ≥5% of immune cells); time from cystectomy to first ctDNA+ sample (≤20 vs >20 wk). b Time from randomization to first clinically meaningful deterioration (≥10-point decrease) at either: ≥2 consecutive visits; or at 1 visit followed by death due to cancer progression ≤8 wk from last deteriorated PRO visit. NE, not evaluable.

BACKGROUND:Durvalumab combined with gemcitabine-cisplatin (GC) has become the standard first-line treatment for advanced biliary tract cancer (BTC) following the TOPAZ-1 trial. However, real-world effectiveness, safety, and prognostic determinants, particularly in underrepresented populations, remain insufficiently defined. The aim of this study was to evaluate the real-world outcomes of first-line durvalumab plus chemotherapy and identify independent prognostic factors in patients with advanced BTC. METHODS:This multicenter retrospective cohort study included patients with unresectable or metastatic BTC treated with first-line durvalumab plus chemotherapy across 21 tertiary oncology centers in Türkiye. Clinical characteristics, laboratory parameters, biomarker data, and treatment details were collected. The primary endpoint was overall survival (OS), while secondary endpoints included progression-free survival (PFS), objective response rate (ORR), and safety. Survival outcomes were analyzed using the Kaplan-Meier method and Cox proportional hazards regression models. RESULTS:A total of 78 patients were analyzed; 53.8% were male, and the median age was 62 years. Primary tumor sites were intrahepatic (55.1%), extrahepatic (30.8%), and gallbladder (14.1%). After a median follow-up of 12.58 months, median OS was 11.59 months and median PFS was 6.80 months. The ORR was 50.6%, including complete and partial responses in 2.7% and 47.9% of patients, respectively. Treatment-related adverse events occurred in 97.4% of patients, with grade 3-4 events in 37.2%. Immune-related adverse events were observed in 19.2%, including one case of grade 3 pneumonitis. No patient permanently discontinued durvalumab due to toxicity, and no durvalumab-related mortality occurred. In multivariable analysis, ECOG performance status 2 (HR 3.43; 95% CI 1.33-8.80) and ALBI grade 2-3 (HR 2.54; 95% CI 1.24-5.19) independently predicted worse OS, while ECOG performance status 2 also predicted shorter PFS (HR 5.91; 95% CI 2.30-15.17). CONCLUSIONS:In this multicenter real-world Turkish cohort, first-line durvalumab plus chemotherapy showed effectiveness and tolerability comparable to clinical trial data. Baseline ECOG performance status and ALBI grade were independent prognostic factors, supporting their use for risk stratification in advanced biliary tract cancer.

ImportanceClinical trials are vital for advancing cancer treatments and improving patient outcomes. Understanding the factors that influence participants’ decision-making is critical for enhancing trial recruitment.ObjectiveTo evaluate the attitudes of patients with cancer and their relatives toward clinical trial participation, identifying key barriers and motivators that affect their willingness to engage in such trials.Design, Setting, and ParticipantsThis cross-sectional survey study was conducted between April 2020 and April 2021. Face-to-face questionnaires were administered by physicians across 6 tertiary hospital medical oncology departments in Turkey. Adults with cancer and their relatives were recruited. Data were analyzed from April to December 2021.ExposureParticipants’ knowledge, perceptions, and motivations regarding clinical trial participation were assessed through a structured questionnaire.Main Outcomes and MeasuresParticipants’ demographic information, their willingness to participate in clinical trials, their perceptions about the clinical trial participation, and the facilitators and barriers to participation.ResultsA total of 978 participants were surveyed, with a median (range) age of 52 (18-82) years; 485 (49.6%) were male and 479 (49.0%) female. Of these, 578 (59.1%) were patients with cancer and 382 (39.1%) family members. Prior clinical trial experience was reported by 174 participants (17.8%), and 428 (43.8%) expressed a willingness to participate in clinical trials. Participants well-informed about clinical trials showed higher willingness (50 of 87 [57.5%] very willing) compared with those with no knowledge (27 of 303 [8.9%] very willing) (χ2 = 275.095; P < .001). Greater willingness was observed in participants from less developed cities compared with the most developed cities (88 of 321 [27.4%] vs 94 of 615 [15.3%]; χ2 = 21.093; P < .001), in individuals with a high school degree or greater compared with those with less than a high school degree (105 of 489 [21.5%] vs 76 of 452 [16.8%]; χ2 = 33.311; P < .001), in those with monthly incomes above compared with below the poverty line (81 of 409 [19.8%] vs 100 of 512 [19.5%]; χ2 = 16.145; P = .003), in those without prior cancer treatment compared with those with prior cancer treatment (125 of 591 [21.2%] vs 40 of 289 [13.8%]; χ2 = 13.801; P = .008), and in participants with prior trial experience compared with those without (74 of 166 [44.6%] vs 111 of 786 [14.1%]; χ2 = 87.771; P < .001). Participants were motivated by potential personal health benefits (604 [61.8%]) and access to new treatments (522 [53.4%]). The primary concerns included potential adverse effects (555 [56.7%]), feeling like a “test subject” (284 [29.0%]), and the risk of receiving a placebo (197 [20.1%]).Conclusions and RelevanceIn this survey study of patients with cancer and their relatives, significant gaps in knowledge and persistent concerns about clinical trial safety were highlighted, impacting participation. Addressing these concerns through targeted education and transparent communication is essential for improving participation rates and ensuring more inclusive cancer research.

Talazoparib is a strong PARP inhibitor with significant catalytic inhibition as well as the ability to cause PARP entrapment at DNA damage sites. It is one of the recommended treatments for individuals with BRCA-mutant advanced breast cancer, although research on its efficacy in advanced ovarian cancer is limited. The purpose of this study was to evaluate the efficacy of talazoparib in advanced breast and ovarian cancer patients with BRCA mutations. Patients with advanced breast (HR + or TNBC) and ovarian cancer who had germline BRCA mutations were included in this multicenter, retrospective study. There were no exclusion criteria regarding treatment-line, metastatic sites or performance status. All patients received talazoparib treatment via early-access programme. The primary endpoint was PFS. Secondary endpoints were OS and ORR. There were 47 and 42 patients in the breast cancer (BC) and ovarian cancer (OC) cohorts, respectively. In BC cohort, after median 13.6 months follow-up the median PFS was 6.5 months (5.0–8.1 months, 95

LBA248 Background: Effective treatment options remain an unmet need for patients (pts) with microsatellite stable/mismatch repair proficient (MSS/pMMR) metastatic colorectal cancer (mCRC). Combination therapy with the anti–lymphocyte activation gene (LAG)-3 antibody favezelimab (fave) and the PD-1 inhibitor pembrolizumab (pembro), has shown promising antitumor activity and manageable safety in PD-L1 CPS ≥1 MSS/pMMR mCRC. The phase 3 KEYFORM-007 study (NCT05064059) evaluated the efficacy and safety of co-formulated fave/pembro vs standard-of-care (SOC) in PD-L1–positive MSS/pMMR mCRC. We present results of the pre-specified final analysis of OS. Methods: Eligible pts with PD-L1 CPS ≥1, MSS/pMMR unresectable mCRC (Stage IV per AJCC 8 th edition), who had progressed on or after, or could not tolerate standard treatment were randomized 1:1 to co-formulated fave 800 mg/pembro 200 mg IV Q3W (Arm A) or SOC (regorafenib 160 mg PO Q4W [QD on days 1-21] or TAS-102 35 mg/m 2 PO Q4W [BID on days 1-5 and 8-12]) (Arm B). Randomization was stratified by geographic region, presence or absence of liver metastases, and time from initial diagnosis of metastatic disease to randomization. Treatment continued for up to 35 cycles or until unacceptable toxicity, progression, confirmed CR (Arm A), or withdrawal. The primary endpoint was OS. The data cut-off was August 15, 2024. Secondary endpoints included PFS, ORR, and DOR (central review, RECIST v1.1 [assessed at interim analysis with data cut-off of August 21, 2023]), and safety. Results: At final analysis, 441 pts (63% male; 59% RAS mutant) were randomized (221 fave/pembro; 220 SOC. Median follow-up was 28 mo (range, 21-32). Median OS was not superior with fave/pembro vs SOC (median 7.3 vs 8.5 mo; HR 0.98; 95% CI, 0.80-1.20; P = 0.4183) in pts with MSS/pMMR mCRC. PFS was not superior with fave/pembro vs SOC (median 2.1 vs 2.6 mo; HR 1.34; 95% CI, 1.09-1.64; nominal P = 0.997). Per protocol, PFS was not tested for statistical significance. A confirmed objective response occurred in 15 (14PR; 1CR [6.8%]) vs 2 (2PR; [0.9%]) pts in the fave/pembro and SOC arms, with best response of PD occurring in 143 (65%) vs 94 (43%) pts, respectively. Median DOR was not reached ([NR] range, 1.8 to 16.8+) among the 15 responders in the fave/pembro arm, and was 6.5+ mo and 12.4 mo, for the 2 responders in the SOC arm. At final analysis, treatment-related adverse events (TRAEs) occurred in 145 (66%) vs 167 (80%) pts, respectively (grade ≥3 in 44 [20%] vs 76 [36%] pts). Adverse events of special interest occurred in 84 (38%) vs 13 (6%) pts, respectively. Conclusion: At final analysis, co-formulated fave/pembro did not improve OS vs SOC in pts with PD-L1-positive MSS/pMMR mCRC. The safety profile was manageable with no new safety signals observed. Clinical trial information: NCT05064059 .