American Journal of Clinical Oncology-Cancer Clinical Trials最新文献

{"title":"Outcomes With Immunotherapy in Hormone Receptor-Positive Breast Cancer: A Systematic Review and Meta-Analysis.","authors":"Moazzam Shahzad, Muhammad K Amin, Amir Kasaeian, Syed M Tariq, Iman M Oskouie, Umar Akram, Nouman Aziz, Sarmad Z Warraich, Muhammad F Khalid, Iqra Anwar, Muhammad U Mushtaq, Michael Jaglal","doi":"10.1097/COC.0000000000001274","DOIUrl":"10.1097/COC.0000000000001274","url":null,"abstract":"<p><strong>Objectives: </strong>Hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) breast cancer has historically shown limited response to immunotherapy. We conducted a systematic review and meta-analysis to evaluate the efficacy and safety of immunotherapy in this patient population.</p><p><strong>Methods: </strong>A systematic search of PubMed, Embase, MEDLINE, ClinicalTrials.gov, and Cochrane Library was conducted through May 2025, following PRISMA guidelines. Eligible studies included clinical trials assessing immunotherapy, either alone or in combination, in HR+/HER2- breast cancer, reporting clinical outcomes. Meta-analyses were performed using random-effects models, with pooled risk ratios (RRs) and event rates. Heterogeneity was assessed using I ² statistics.</p><p><strong>Results: </strong>A total of 11 randomized controlled trials involving 7480 patients (3742 immunotherapy, 3738 control) were included. Immunotherapy did not significantly improve overall response rate (RR: 1.20; 95% CI: 0.92-1.55) or partial response rate (RR: 1.03; 95% CI: 0.54-1.94) compared with control, though it was associated with improved complete response (RR: 1.63; 95% CI: 1.34-1.97). Immunotherapy was also associated with higher therapy-related adverse events (RR: 1.29; 95% CI: 1.04-1.60). Pooled median overall survival and progression-free survival were 23.6 and 6.6 months, respectively. The pooled complete response, partial response, stable disease, and progressive disease rates were 9, 27, 51, and 23%, respectively. Overall mortality in the immunotherapy group was 4%.</p><p><strong>Conclusions: </strong>Immunotherapy may modestly enhance complete response rates in HR+/HER2- breast cancer but is associated with increased toxicity and lacks consistent improvements in overall or progression-free survival. Further biomarker-driven trials are warranted.</p>","PeriodicalId":50812,"journal":{"name":"American Journal of Clinical Oncology-Cancer Clinical Trials","volume":" ","pages":"297-307"},"PeriodicalIF":1.8,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147950179","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Pilot Feasibility and Acceptability Study of a Structured Nurse-Led Family Caregiver Program Among Caregivers of Hospitalized Cancer Patients.","authors":"James Raj K, Preeti R Bhupali","doi":"10.1097/COC.0000000000001326","DOIUrl":"10.1097/COC.0000000000001326","url":null,"abstract":"<p><strong>Introduction: </strong>Family caregivers of hospitalized cancer patients play a vital role in supporting patient care, but often experience considerable burden, stress, and reduced quality of life due to limited preparation and a lack of structured professional support.</p><p><strong>Objectives: </strong>To assess the feasibility and acceptability of a structured nurse-led family caregiver program and to explore preliminary trends in caregiver burden, stress, and quality of life.</p><p><strong>Methods: </strong>A pre-experimental 1-group pretest-posttest design was used. Fifteen family caregivers of hospitalized cancer patients were recruited from a tertiary care hospital in Bangalore using purposive sampling. Standardized tools, including the Zarit Burden Interview, DASS-21 stress subscale and WHOQOL-BREF were administered before and after the intervention. The nurse-led caregiver program was delivered through face-to-face sessions during hospitalization. Descriptive statistics were used for data analysis.</p><p><strong>Results: </strong>The intervention was feasible to deliver within routine hospital schedules, and all participants completed the study. Posttest scores showed a reduction in caregiver burden and stress levels, along with an improvement in quality-of-life scores.</p><p><strong>Conclusions: </strong>The structured nurse-led family caregiver program was feasible and acceptable in the hospital setting. The findings support conducting a larger study to evaluate the effectiveness of the intervention.</p>","PeriodicalId":50812,"journal":{"name":"American Journal of Clinical Oncology-Cancer Clinical Trials","volume":" ","pages":"295-296"},"PeriodicalIF":1.8,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147717445","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hepatotoxicity of External Radiotherapy for Hepatocellular Carcinoma in the Setting of Prior Yttrium-90 Radioembolization.","authors":"Sarah Feldkamp, Claire Niewiara, Bailey Nelson, Kyle Wang, Bashar Nahab, Darren Lee, Nedas Semaska, Ismael Assi, Jordan Kharofa","doi":"10.1097/COC.0000000000001300","DOIUrl":"10.1097/COC.0000000000001300","url":null,"abstract":"<p><strong>Objectives: </strong>To evaluate the hepatotoxicity and clinical outcomes following external beam radiation therapy (EBRT) in patients with hepatocellular carcinoma (HCC) previously treated with Yttrium-90 radioembolization (Y-90), a setting in which cumulative liver radiation exposure raises concern for increased toxicity risk.</p><p><strong>Methods: </strong>We performed a retrospective review of 94 HCC patients treated with EBRT from 2016 to 2024, including 15 treated with Y-90. Hepatotoxicity was assessed using Albumin-Bilirubin (ALBI) score changes at 3 and 6 months post-EBRT. Secondary outcomes included CTCAE toxicity, local control, and survival. Treatment details, prior locoregional therapies, and dosimetric parameters were collected. Fisher exact tests and Kaplan-Meier analyses were used for statistical comparisons.</p><p><strong>Results: </strong>Baseline demographics and liver function were similar between groups. Over half the Y-90 cohort (53%) received fractionated proton therapy. At 6 months, grade 1 and 2 ALBI deterioration occurred in 2 (13%) and 4 patients (27%) with prior Y-90, compared with 17 (22%) and 21 patients (27%) without prior Y-90 ( P =0.77). Grade ≥2 CTCAE toxicity occurred in 2 patients (13%) with prior Y-90 and in 5 patients (6%) without. Local control was 92% with no local failures in patients treated after Y-90. Median OS was 39 months without prior Y-90 and 34 months with prior Y-90 ( P =0.89).</p><p><strong>Conclusions: </strong>EBRT following Y-90 was not associated with increased hepatotoxicity or inferior oncologic outcomes compared with EBRT alone. When delivered with individualized planning, including fractionation, EBRT represents a safe and effective salvage modality for patients with residual or recurrent HCC after Y-90.</p>","PeriodicalId":50812,"journal":{"name":"American Journal of Clinical Oncology-Cancer Clinical Trials","volume":" ","pages":"275-280"},"PeriodicalIF":1.8,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146151194","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Conditional Survival Estimates for Malignant Glioma Patients: Secondary Analysis of RTOG 9006.","authors":"Matthew H Brown, Hua-Ren R Cherng, James W Assif, Kai Sun, Mark V Mishra","doi":"10.1097/COC.0000000000001296","DOIUrl":"10.1097/COC.0000000000001296","url":null,"abstract":"<p><strong>Objectives: </strong>Conditional survival (CS) provides estimates of how survival changes over time. The primary objective of this secondary analysis is to report CS estimates for patients with malignant gliomas enrolled on RTOG 9006.</p><p><strong>Methods: </strong>A post hoc analysis of RTOG 9006 was performed using data obtained from the NCI NCTN Data Archive. Eligible patients included those enrolled on RTOG 9006 (n=632). CS estimates from the time of diagnosis and following 1, 3, and 5 years of survival were calculated using Kaplan-Meier. Multivariable Cox proportional hazards modeling multivariate analysis (MVA) was performed to evaluate the prognostic significance of age, KPS, treatment arm, histology, and extent of surgical resection following 1, 3, and 5 years of survival. The RPA class was evaluated on univariate analysis following the same initial survival periods.</p><p><strong>Results: </strong>Among 632 patients, OS at 1 and 3 years was 50.9% and 17.3%, respectively. CS improved over time, with patients who survived the first year having a 46.4% chance of surviving an additional year and 82.9% chance for those who had already survived 3 years. Age, KPS, and extent of surgical resection were significant predictors of OS at diagnosis but prognostic value declined over time. Glioblastoma multiforme (GBM) histology was significant at all time points. Patients who survived 3 years had significantly improved additional survival with conventional fractionation compared with hyperfractionation. In addition, RPA lost prognostic significance over time.</p><p><strong>Conclusions: </strong>Given the diminishing influence of KPS and surgical resection, treatment decisions should be based on individualized approaches considering evolving survival probabilities, not solely initial prognosis.</p>","PeriodicalId":50812,"journal":{"name":"American Journal of Clinical Oncology-Cancer Clinical Trials","volume":" ","pages":"264-267"},"PeriodicalIF":1.8,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147482309","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Emergence of Single-Week Adjuvant Radiation Therapy for Early-Stage Breast Cancer in the United States.","authors":"Nimisha Kasliwal, Marie Gordon, Evan Becker, Kai Ding, Shearwood McClelland","doi":"10.1097/COC.0000000000001336","DOIUrl":"https://doi.org/10.1097/COC.0000000000001336","url":null,"abstract":"<p><strong>Objectives: </strong>Over the past 2 decades, adjuvant radiation therapy (RT) for early-stage breast cancer has shifted toward shorter regimens. While initially occurring over 5 to 6 weeks, level 1 evidence has supported the equivalence of 3 to 4 weeks of adjuvant RT. More recently, level 1 evidence has demonstrated equivalence of 1-week ultrahypofractionated RT (UHRT) to 3-week adjuvant RT. This study evaluates the adoption of UHRT in the United States before, during, and after the COVID-19 pandemic.</p><p><strong>Methods: </strong>Patients with early-stage breast cancer who received lumpectomy and adjuvant RT from 2018 to 2022 were assessed using the National Cancer Database (NCDB). UHRT was defined as 5.2 Gy per fraction with a total dose of 26 Gy. Data were grouped as prepandemic (2018 to 2019), pandemic (2020), and postpandemic (2021 to 2022). The adoption of UHRT and RT completion rates was assessed among these periods.</p><p><strong>Results: </strong>Before, during, and after the pandemic, 0.98% (133/13,154), 4.88% (303/6208), and 14.27% of patients (2044/14,321) underwent UHRT, respectively (P<0.0001). Cumulative RT completion rates were 94.85% before the pandemic, 96.10% during the pandemic, and 96.83% after the pandemic (P<0.0001), demonstrating a significant increase in adoption. For UHRT, completion rates were 100.00% prepandemic, 99.34% during the pandemic, and 99.46% postpandemic (P=0.6651), higher than overall RT completion rates across all 3 periods.</p><p><strong>Conclusion: </strong>Nationwide data demonstrates a 14-fold increase in the use of UHRT from 2018 to 2022. Despite this increase and the near 100% completion rates for UHRT, UHRT remains underutilized compared with standard and hypofractionated regimens. These findings indicate fertile ground for increased UHRT adoption in breast cancer care nationwide.</p>","PeriodicalId":50812,"journal":{"name":"American Journal of Clinical Oncology-Cancer Clinical Trials","volume":" ","pages":""},"PeriodicalIF":1.8,"publicationDate":"2026-05-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148303919","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"American Radium Society (ARS) Appropriate Use Criteria (AUC) for Low-Dose Radiotherapy for Treatment of Osteoarthritis.","authors":"Austin Dove, Bobby Koneru, William Small, Amanda E Nelson, Jean L Wright, Matlock Jeffries, Phillip Bennion, Craig Jones, Shauna R Campbell, Rahul Tendulkar, Suzanne Russo, Scott Lester, Krishan Jethwa, Catherine Hofstetter, Tom Appleton, Richard Shaffer","doi":"10.1097/COC.0000000000001333","DOIUrl":"https://doi.org/10.1097/COC.0000000000001333","url":null,"abstract":"<p><strong>Objectives: </strong>To summarize current evidence for radiotherapy in the treatment of OA. The population, intervention, comparator, and outcome questions included: What is the role of LDRT for treatment of OA?; What are risks of LDRT?; and What are the optimal RT techniques for OA?</p><p><strong>Methods: </strong>This multispecialty-led committee includes radiation oncologists, rheumatologists, orthopedic surgeons, and a patient advocate. Using the population, intervention, comparator, outcome, timing and study design (PICOTS) framework, evidence regarding treatment outcomes was assessed using Cochrane and PRISMA methodology. Eligible studies included prospective and retrospective (n≥50) studies published between January 1, 2010, and May 10, 2025, from Embase, Medline, and PubMed databases. Study type and quality were assessed. Well-established RAND-UCLA consensus methodology (modified Delphi) was used to rate the appropriateness of the treatment options.</p><p><strong>Results: </strong>Of the 548 articles identified using the search strategy, 44 were selected for inclusion. Eight additional studies were identified through backward citation searching. Ten well-designed studies accounting for biases, 15 moderately well-designed studies accounting for the most common biases, 18 studies with design limitations, 8 supplemental studies not useful as primary evidence, and 1 meta-analysis were included. Additional studies were included to provide context and were not used to guide recommendations. The results of this analysis demonstrate that LDRT results in an overall treatment response rate of 60% to 90%, with significant clinical benefits including pain reduction, increased joint mobility, and improved quality of life.</p><p><strong>Conclusions: </strong>This systematic review and consensus guidelines for LDRT treatment of OA are based on current evidence. Further high-quality studies are warranted.</p>","PeriodicalId":50812,"journal":{"name":"American Journal of Clinical Oncology-Cancer Clinical Trials","volume":" ","pages":""},"PeriodicalIF":1.8,"publicationDate":"2026-05-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148018571","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Landscape of Clinical Trials for TCR-T Cell Therapy.","authors":"Xingcan Fan, Tao Yu, Qiuyu Liao, Yulin Song, Gang Liu","doi":"10.1097/COC.0000000000001335","DOIUrl":"https://doi.org/10.1097/COC.0000000000001335","url":null,"abstract":"<p><p>T cell receptor-engineered T cell (TCR-T) therapy represents an innovative tumor immunotherapy. Distinct from CAR-T, it recognizes MHC-restricted antigens to target tumor-specific antigens, exhibiting unique advantages for both solid and hematologic malignancies. To clarify the main trends, key targets, and therapeutic indications of TCR-T therapy, this study systematically summarizes the landscape of TCR-T-targeted clinical trials based on rigorous screening of the Trialtrove database, including 260 trials before April 1, 2026. Descriptive statistics were used to analyze the trials in terms of phase, status, distribution, disease indications, primary targets, and investigational drugs. Overall, TCR-T clinical research maintains sustained enthusiasm, dominated by early-phase trials (phase I and phase I/II, accounting for 88.85%), with active trials (open and planned) accounting for 51.92% and a considerable proportion of terminated trials (21.92%). Geographically, trials are concentrated in the United States and China, which serve as core collaboration nodes, with obvious geographical clustering characteristics in regional collaboration networks. In terms of disease indications, TCR-T therapy is more focused on solid tumors, with unspecified solid tumor, non-small cell lung cancer, and head/neck cancer as the top 3 indications. NY-ESO-1 is the most prominent target, followed by MAGE-A4, KRAS, PRAME, HPV16 E6/E7, and HBV surface antigen, with letetresgene autoleucel and LioCyx-M004 being the most investigated TCR-T products. Collectively, TCR-T therapy is a promising field in tumor immunotherapy with continuous research investment and advancing clinical progress.</p>","PeriodicalId":50812,"journal":{"name":"American Journal of Clinical Oncology-Cancer Clinical Trials","volume":" ","pages":""},"PeriodicalIF":1.8,"publicationDate":"2026-05-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148018565","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comorbidity Burden, Treatment, and Survival Among Screen-Detected Lung Cancer Patients: Implications for USPSTF Guidelines.","authors":"Norah Powell, Madeleine Hinojos, Shruti Ayyalasomayajula, Sarah Mikesell, David Stenehjem, Mary J Boylan, Nils D Arvold","doi":"10.1097/COC.0000000000001334","DOIUrl":"https://doi.org/10.1097/COC.0000000000001334","url":null,"abstract":"<p><strong>Objectives: </strong>Current US Preventive Services Task Force (USPSTF) guidelines for lung cancer screening restrict low-dose chest CT (LDCT) eligibility to those willing to undergo surgery. Little is known about comorbidities, treatment, and lung cancer outcomes among LDCT-screened patients.</p><p><strong>Methods: </strong>This retrospective cohort study examined all patients diagnosed with lung cancer within a prospective registry of 1805 consecutive LDCT-screened patients from March 1, 2015, to March 1, 2020, in a single large health care system. We assessed baseline comorbidity burden, pulmonary function, treatment, and survival, including a prespecified focus on patients with American Joint Committee on Cancer stage I non-small cell lung cancer (NSCLC).</p><p><strong>Results: </strong>Thirty-eight patients had LDCT-detected lung cancer; median age was 69.7, median pack-years smoked was 40.0, 47.4% had emphysema, median Charlson-Deyo score was 4, and 23.7% underwent surgery. Among patients with stage I NSCLC who either received surgery (n=6) or stereotactic body radiotherapy (SBRT; n=11), a trend for surgery-treated patients to have higher performance status, higher baseline pulmonary function, and lower Charlson-Deyo score was observed. After a median follow-up of 63 months, lung cancer-specific survival was 66.7% versus 90.9% for surgery versus SBRT, while median overall survival was 82.2 versus 42.9 months (P=0.26).</p><p><strong>Conclusions: </strong>Over three-quarters of community patients with LDCT-detected lung cancer do not receive surgery. Despite generally higher comorbidity, patients with early-stage disease receiving SBRT survived several yearsand had numerically higher lung cancer-specific survival than patients receiving surgery. Restricting LDCT screening to surgical candidates may not reflect modern outcomes.</p>","PeriodicalId":50812,"journal":{"name":"American Journal of Clinical Oncology-Cancer Clinical Trials","volume":" ","pages":""},"PeriodicalIF":1.8,"publicationDate":"2026-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148018500","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Immunotherapy in Extensive Stage Small-Cell Lung Cancer in First-Line and Second-Line Setting: A Systematic Review and Meta-Analysis.","authors":"Nupur Krishnan, Patsy Lee, Gabriel Boldt, Suganija Lakkunarajah, Saurav Verma, Phillip Blanchette, Jacques Raphael","doi":"10.1097/COC.0000000000001265","DOIUrl":"10.1097/COC.0000000000001265","url":null,"abstract":"<p><strong>Objectives: </strong>Despite a good response to first-line chemotherapy, small-cell lung cancer (SCLC) has high relapse rates and a poor prognosis. We conducted a systematic review and meta-analysis to assess the role of immune checkpoint inhibitors (ICIs) in the treatment of extended stage SCLC (ES-SCLC), in different lines of therapy.</p><p><strong>Methods: </strong>Medline (PubMed), EMBASE, and Cochrane Library databases between January 2010 and March 2025 and conference proceedings between 2018 and 2025 were searched for RCTs assessing ICIs versus chemotherapy in patients with ES-SCLC. Primary endpoints were overall survival (OS) and progression-free survival (PFS). Secondary endpoints included objective response rate (ORR) and grade 3+ adverse events. Pooled hazard ratios (HR) for OS and PFS were meta-analyzed using the generic inverse variance method, and random-effect models were used to compute pooled estimates. Subgroup analyses compared survival by line of therapy, sex, age, and ECOG status.</p><p><strong>Results: </strong>ICIs decreased risk of death by 19% (HR: 0.81, 95% CI: 0.76-0.86). OS benefit was regardless of age, sex, or ECOG, but only in first-line treatment. ICIs decreased the risk of disease progression by 22% (HR: 0.78, 95% CI: 0.67-0.91), with PFS benefit restricted to first-line treatment with a detrimental effect in the second line. ICIs improved ORR (OR: 0.79, 95% CI: 0.66-0.95), but were associated with increased grade 3+diarrhea (OR: 3.63, 95% CI: 1.46-9.02).</p><p><strong>Conclusions: </strong>ICIs conferred efficacy benefits and an acceptable safety profile in the treatment of patients with ES-SCLC in the first-line, but should not be used in the second-line as single agents. Biomarkers predicting long-term benefit are needed to further improve outcomes.</p>","PeriodicalId":50812,"journal":{"name":"American Journal of Clinical Oncology-Cancer Clinical Trials","volume":" ","pages":"219-228"},"PeriodicalIF":1.8,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145716535","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Phase 2 Trial of Protein Kinase C Iota Inhibition With the Combination of Auranofin and Sirolimus in Patients With Recurrent Ovarian Cancer.","authors":"Aminah Jatoi, Nathan R Foster, Andrea Wahner Hendrickson, Matthew S Block, S John Weroha, Erik J Asmus, Nicole R Murray, Alan P Fields","doi":"10.1097/COC.0000000000001263","DOIUrl":"10.1097/COC.0000000000001263","url":null,"abstract":"<p><strong>Objectives: </strong>This trial served as a proof-of-concept for whether inhibition of protein kinase C iota (PKCι) with auranofin and sirolimus provide antineoplastic effects in patients with recurrent high-grade serous ovarian cancer.</p><p><strong>Methods: </strong>This drug combination was administered to patients with recurrent high-grade serous ovarian cancer. Dosing was based on unpublished phase 1 data and consisted of auranofin 6 mg and sirolimus 5 mg both orally per day of a 28-day cycle. The primary endpoint was tumor response. Available tumor tissue was assessed for PKCι protein expression by immunohistochemistry (IHC) and PRKCI copy number by fluorescence in-situ hybridization (FISH) after the start of cancer therapy.</p><p><strong>Results: </strong>Twenty-two patients were enrolled, and 21 were evaluable for all clinical trial endpoints. One patient was unevaluable because she did not receive a full chemotherapy cycle. No tumor responses were seen in the first 21 patients, resulting in early trial termination per a priori trial design. The median progression-free survival was 2.1 months (95% CI: 1.8-3.7). The median overall survival was 4.4 months (95% CI: 2.6-12.5). Fourteen (67%) patients had at least one grade 3 or worse adverse event. Nineteen of 21 evaluable patients had available tumor tissue, which showed the median PKCι copy number averaged per cell of 3 (range: 2 to 7), and PKCι expression (at least 1+) in all.</p><p><strong>Conclusions: </strong>As prescribed here, auranofin and sirolimus manifested no antineoplastic activity in patients with recurrent high-grade serous ovarian cancer that expressed PKCι.</p>","PeriodicalId":50812,"journal":{"name":"American Journal of Clinical Oncology-Cancer Clinical Trials","volume":" ","pages":"238-242"},"PeriodicalIF":1.8,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145330931","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}