Oncology and Therapy最新文献

{"title":"A Cross-Sectional Study of Variant Interpretation and Reporting of NGS Data Using Tertiary Analysis Software: Navify^® Mutation Profiler.","authors":"Francesco Pepe, Gianluca Russo, Nadia Barraco, Marco Bono, Angela Listì, Luisella Righi, Dario de Biase, Thais Maloberti, Claudia Scimone, Lucia Palumbo, Danilo Rocco, Giuseppina Roscigno, Enzo Gallo, Simonetta Buglioni, Michelina Coco, Lucia Anna Muscarella, Giancarlo Troncone, Umberto Malapelle","doi":"10.1007/s40487-024-00316-0","DOIUrl":"10.1007/s40487-024-00316-0","url":null,"abstract":"<p><strong>Introduction: </strong>Personalized medicine has revolutionized the clinical management of patients with solid tumors. However, the large volumes of molecular data derived from next-generation sequencing (NGS) and the lack of harmonized bioinformatics pipelines drastically impact the clinical management of patients with solid tumors. A possible solution to streamline the molecular interpretation and reporting of NGS data would be to adopt automated data analysis software. In this study, we tested the clinical efficiency of the Navify Mutation Profiler (nMP) software in improving the interpretation of NGS data analysis in diagnostic routine samples from patients with solid tumors.</p><p><strong>Methods: </strong>This study included one coordinating institution (Federico II University of Naples) and five other Italian institutions. Variant call format (VCF) files from reference standard samples previously tested by the coordinating institution and from n = 8 diagnostic routine samples (n = 2 from colorectal carcinoma; n = 2 from non-small cell lung cancer; n = 2 from advanced melanoma; and n = 2 from patients with gastrointestinal stromal tumors) and previously analyzed by each participating institution (n = 5) with standardized internal analysis workflows were uploaded onto the Navify^® Mutation Profiler (nMP) system (Roche Sequencing Solutions, Pleasanton, CA, USA) for automated analysis and interpretation of DNA and RNA molecular alterations analytical parameters, molecular profiling, and clinical interpretation were carried out by the nMP system and compared with the standard workflow data analyzed by the participating institutions.</p><p><strong>Results: </strong>Overall, all VCF files were successfully submitted and interpreted by the nMP system. A concordance agreement rate of 89.6% was observed between the automated and standard workflow systems. In particular, DNA and RNA molecular profiles obtained with the nMP system matched those obtained with standardized approaches in 44 out of 48 patients (91.7%) and in 11 out of 12 (91.7%) cases, respectively. In addition, the nMP system evidenced wild-type variants in 6 out of 7 (85.7%) cases.</p><p><strong>Conclusions: </strong>The nMP system represents a valid, easily manageable, and clinically useful system to interpret NGS data on diagnostic routine samples from patients with solid tumors.</p>","PeriodicalId":44205,"journal":{"name":"Oncology and Therapy","volume":" ","pages":"115-130"},"PeriodicalIF":3.2,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11880482/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142740893","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Real-World Observational Study of Incidence and Outcomes in an HR+/HER2- Early Breast Cancer Population with High-Risk of Recurrence in Finland.","authors":"Ravinder Singh, Samuli Tuominen, Mariann I Lassenius, Merja Auvinen, Astrid Torstensson, Tom Wiklund","doi":"10.1007/s40487-024-00324-0","DOIUrl":"10.1007/s40487-024-00324-0","url":null,"abstract":"<p><strong>Introduction: </strong>Real-world data on patients with early breast cancer (EBC) with high-risk features remains limited. This population-based study determined the incidence, outcomes and characteristics of patients with hormone receptor (HR)-positive, human epidermal growth factor 2 receptor (HER2)-negative EBC with high-risk features treated in everyday clinical care in two Finnish hospital districts which represent approximately 40% (2.5 million) of the total Finnish population (5.5 million).</p><p><strong>Methods: </strong>Adult female patients with BC (ICD-10 C50*) diagnosed between January 2012-June 2019 were indexed at the first BC diagnosis and followed until December 2019 or death. EBC was defined as having no records of metastasis within 90 days of index. High-risk status was defined as ≥ 4 positive axillary lymph nodes (ALNs) or 1-3 ALNs with either grade 3 tumor or tumor size ≥ 5 cm. Outcomes included invasive disease-free survival (IDFS), distant relapse-free survival (DRFS) and overall survival (OS) and were assessed using Kaplan-Meier methods and Cox regression models.</p><p><strong>Results: </strong>Among the 8678 patients with HR+/HER2- EBC, risk classification was feasible in 8081 (93.1%) individuals. Of these, 1407 (17.4%) were defined as high-risk and the remaining 6674 (82.6%) as low-risk patients. The average annual incidence of high-risk HR+/HER2- EBC in 2012-2018 was 21.8/100,000 women. Five-year invasive disease-free survival (IDFS) and distant recurrence-free survival (DRFS) showed higher risk of recurrence for the high-risk group: IDFS 79.7% (95% CI 77.0-82.2) vs 89.3% (88.3-90.2) in the low-risk group; DRFS 82.4% (79.7-84.7) vs 92.9% (92.1-93.7) in the low-risk. Five-year overall survival (OS) in the high-risk group was 89.5% (87.3-91.4) and was 95.4% (94.7-96.0) in the low-risk group.</p><p><strong>Conclusions: </strong>This study showed that high-risk patients account for 17% of newly diagnosed HR+/HER2- EBC in Finland. The high-risk profile was associated with increased risk of recurrence, distant relapse and death compared to low-risk patients. The poorer outcomes of high-risk HR+/HER2- EBC emphasizes a clear unmet need in improving the identification and treatment of these patients.</p>","PeriodicalId":44205,"journal":{"name":"Oncology and Therapy","volume":" ","pages":"185-200"},"PeriodicalIF":3.2,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11880475/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143415719","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Podcast Discussion on the Intracranial Efficacy of Antibody-Drug Conjugates in Patients with EGFR-Mutated NSCLC with Brain Metastases.","authors":"Melissa L Johnson, Jessica J Lin, Adrienne Boire, Melin J Khandekar, Helena A Yu","doi":"10.1007/s40487-024-00315-1","DOIUrl":"10.1007/s40487-024-00315-1","url":null,"abstract":"<p><p>The incidence of brain metastases is higher in patients with non-small cell lung cancer (NSCLC) than in patients with most other cancers, and the development of brain metastases is associated with poor prognosis. The objective of the podcast is to provide information about current and future treatments for brain metastases that develop in patients with EGFR-mutated NSCLC. The panel discusses surveillance and management of patients with brain metastases, different types of currently used treatments, and recent data on the intracranial efficacy of antibody-drug conjugates (ADCs). The panel also discusses current and future studies of ADCs in patients with EGFR-mutated NSCLC with brain metastases. This podcast discussion, among four oncologists (two thoracic oncologists, one radiation oncologist, and one neurologist/neuro-oncologist), is for healthcare professionals (HCPs) at community practices and research institutions.</p>","PeriodicalId":44205,"journal":{"name":"Oncology and Therapy","volume":" ","pages":"17-30"},"PeriodicalIF":3.2,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11880489/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142855963","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Liver Metastases are Associated with a Short Post-Progression Survival in a Real-World Group of Patients with Melanoma Treated with Checkpoint Inhibitors.","authors":"Miriam Mengoni, Thomas Tüting, Evelyn Gaffal, Andreas D Braun","doi":"10.1007/s40487-024-00320-4","DOIUrl":"10.1007/s40487-024-00320-4","url":null,"abstract":"<p><strong>Introduction: </strong>The introduction of immunotherapy (IT) has transformed clinical care of patients with metastatic melanoma. However, many patients still die as a result of progressive disease. Here we analyzed how IT improved survival in a real-world setting. Additionally, we investigated whether IT alters the dynamics and pattern of metastatic progression in different organs resulting from tissue-specific immune microenvironments.</p><p><strong>Methods: </strong>We retrospectively compared a group of 61 patients with metastatic melanoma (24 female, 37 male) treated with IT between 2015 and 2018 with a historical control group of 56 patients with metastatic melanoma (21 female, 35 male) treated with chemotherapy between 2005 and 2008 regarding treatment response rates and overall survival as well as the timing and distribution of metastatic progression.</p><p><strong>Results: </strong>Patients with metastatic melanoma treated with IT showed increased response rates and longer overall survival when compared with patients treated with chemotherapy. In addition, treatment with IT altered the dynamics but not the pattern of metastatic progression when compared with treatment with chemotherapy. Interestingly, patients receiving IT lived significantly longer after metastatic progression to lymph nodes, lungs and brain, but not after metastatic progression to the liver.</p><p><strong>Conclusion: </strong>Our results confirm the efficacy of IT in a real-world setting. The altered dynamics of metastases supports studies suggesting a unique role of immune privilege in the liver tissue microenvironment that increases resistance to immunotherapy.</p>","PeriodicalId":44205,"journal":{"name":"Oncology and Therapy","volume":" ","pages":"131-143"},"PeriodicalIF":3.2,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11880473/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142808208","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Optimizing Real-World Outcomes in High-Risk Relapsed/Refractory (r/r) DLBCL with CAR T Cell Therapy: A Vodcast and Case Example.","authors":"Gloria Iacoboni, María Pérez Raya","doi":"10.1007/s40487-024-00319-x","DOIUrl":"10.1007/s40487-024-00319-x","url":null,"abstract":"<p><p>Chimeric antigen receptor (CAR) T-cell therapy is effective in the treatment of patients with diffuse large B cell lymphoma (DLBCL), even those with high-grade disease. However, it has a unique safety profile, including cytokine-release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS), and robust management of these events are important to maximize benefits. The aim of this vodcast is to outline the management of a patient receiving CAR T-cell therapy for relapsed/refractory (r/r) DLBCL. In January 2005, the patient was diagnosed with atypical chronic lymphocytic leukemia (CLL) and treated with two cycles of fludarabine and cyclophosphamide before stopping due to skin toxicity. In 2007, the patient progressed and received alemtuzumab. In January 2018, the patient was diagnosed with DLBCL (nongerminal center, stage IV-A, bone marrow infiltration); a clonality analysis with the previous CLL provided a negative result. In March 2018, the patient received first-line treatment with rituximab-cyclophosphamide-doxorubicin-vincristine-prednisolone (R-CHOP)) for six cycles. At this point, a positron emission tomography (PET) scan showed complete remission. Unfortunately, in December 2018, they experienced a relapse and second-line therapy with rituximab, etoposide, cytarabine, cisplatin, and prednisone (R-ESHAP) was started. Following the second cycle of R-ESHAP in February 2019, the patient progressed, and third-line treatment was provided by rituximab plus ifosfamide, gemcitabine, vinorelbine, and prednisone (R-IGEV) for four cycles. The last cycle of R-IGEV was received in May 2019, but the patient progressed. In July 2019, the patient received a tisagenlecleucel infusion. The authors describe the effectiveness of the CAR T-cell therapy and how the adverse events (AEs) encountered, including CRS and ICANS, were managed. Results from real-world evidence studies of tisagenlecleucel in DLBCL are similar to those observed in the pivotal clinical trials. In conclusion, CAR T-cell therapy can be effective and achieve long-lasting, durable responses in patients with high-risk r/r DLBCL. However, long-term follow up is key to watch out for late AEs and potential lymphoma relapse.</p>","PeriodicalId":44205,"journal":{"name":"Oncology and Therapy","volume":" ","pages":"11-16"},"PeriodicalIF":3.2,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11880491/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142830337","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction: Study on the Impact of Hormone Therapy for Prostate Cancer on the Quality of Life and the Psycho-Relational Sphere of Patients: ProQoL.","authors":"Francesca Cappuccio, Carlo Buonerba, Luca Scafuri, Rossella Di Trolio, Pasquale Dolce, Serena Orsola Trabucco, Filomena Erbetta, Elvira Tulimieri, Antonella Sciscio, Concetta Ingenito, Antonio Verde, Giuseppe Di Lorenzo","doi":"10.1007/s40487-024-00321-3","DOIUrl":"10.1007/s40487-024-00321-3","url":null,"abstract":"","PeriodicalId":44205,"journal":{"name":"Oncology and Therapy","volume":" ","pages":"251"},"PeriodicalIF":3.2,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11880462/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142873016","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The State of the Art of Image Guided Superficial Radiation Therapy Treatment of Non-melanoma Skin Cancer in Outpatient Dermatology Clinics in the United States and Review of the Literature.","authors":"Peyton M Harris, Aaron S Farberg, Janine Hopkins, Liqiao Ma, Donna Serure, Blake Robbins, Candace Osborne, Luis Bravo, Pauline Lausser, Amanda Boatner","doi":"10.1007/s40487-024-00310-6","DOIUrl":"10.1007/s40487-024-00310-6","url":null,"abstract":"<p><strong>Introduction: </strong>Image guided superficial radiation therapy (IGSRT) is a novel technology which combines traditional superficial radiation therapy (SRT) with high resolution dermal ultrasound (HRDUS) to treat non-melanoma skin cancers (NMSC). Since development, IGSRT use has expanded dramatically in outpatient clinics. We review the IGSRT literature and state-of-the-art operating principles in US dermatologic practices.</p><p><strong>Methods: </strong>A literature search of electronic databases (Medline, Pubmed, Cochrane Library, Science Direct) combined with various authors' published and unpublished documents, procedures, and clinical experience with IGSRT were synthesized for this paper.</p><p><strong>Results: </strong>Studies have demonstrated IGSRT consistently delivers high cure rates (> 99%) with low complications for early stage (stage 0, I, or II) squamous cell and basal cell carcinomas. Control rates are statistically superior to non-image guided SRT and external beam radiation (XRT) as well as Mohs micrographic surgery (MMS). This improvement is attributed to in vivo dermal tumor visualization via HRDUS and using an interdisciplinary approach to deliver care. IGSRT use in the dermatologic clinic for early stage NMSCs has become common practice and continues to expand.</p><p><strong>Conclusion: </strong>While the safety and cosmetic benefits of SRT/XRT have been long documented, IGSRT represents a significant leap forward in efficacy (statistically significant) by adding in vivo dermal tumor imaging. Results rival and appear on one study to surpass tumor control obtained with MMS. A contributing factor to the success may be the availability and use of an interdisciplinary team approach that includes dermatologists, radiation therapists, radiation oncologists, and medical physicists. The high tumor control rates, minimal side effects, favorable cosmesis, and ability to treat multiple lesions per session using IGSRT are establishing this modality as a standard first-line therapy for early stage NMSCs in dermatology clinics. IGSRT may represent the most effective option for the non-surgical treatment of early stage NMSC to date.</p>","PeriodicalId":44205,"journal":{"name":"Oncology and Therapy","volume":" ","pages":"31-48"},"PeriodicalIF":3.2,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11880453/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142689228","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Red Blood Cell Distribution Width May Predict Drug-Induced Anemia and Prognosis in Patients Affected by Primary/Secondary Myelofibrosis Treated with Ruxolitinib.","authors":"Alessandro Laganà, Emilia Scalzulli, Ida Carmosino, Maria L Bisegna, Maurizio Martelli, Massimo Breccia","doi":"10.1007/s40487-024-00322-2","DOIUrl":"10.1007/s40487-024-00322-2","url":null,"abstract":"<p><strong>Introduction: </strong>Myelofibrosis (MF) is often characterized by a multifactorial anemia determined, in part, by bone marrow (BM) fibrosis, extramedullary erythropoiesis and splenomegaly. Ruxolitinib (RUX) is the first-in-class janus kinase 2 (JAK2) inhibitor approved for treatment of MF, proved to reduce spleen volume and decrease symptom burden. The red cell distribution width (RDW) is the measure of erythrocyte volume variability (anisocytosis). RDW has been recognized as a marker of clinical and subclinical systemic inflammation, and its elevation has also been associated with poor outcome in a wide spectrum of benign disorders and in different types of neoplasms.</p><p><strong>Methods: </strong>We retrospectively evaluated RDW in a single-center series of 200 consecutive patients with primary and secondary MF at RUX treatment initiation and examined any possible correlation with adverse MF features or drug-related anemia and any prognostic impact.</p><p><strong>Results: </strong>We suggested 20.5% as the optimal cutoff point in RDW values at start of RUX to dichotomize patients in receiver operating characteristic (ROC) analysis for spleen response and for survival. Higher RDW values at RUX start were associated with clinical and laboratory features of an aggressive MF phenotype. Lower spleen response (p < 0.001) and greater odds of drug-related anemia at 3 (p = 0.006) and 6 months (p < 0.001) were also seen in patients with higher RDW. Both increased RDW (considered as a continuous variable) and RDW ≥ 20.5% were associated with shorter overall survival (OS) from RUX initiation in univariate and multivariate analysis: HR 1.25 (95% confidence interval [CI], 1.12-1.40) (p < 0.001) and HR 3.01 (95% CI 1.81-4.99) (p < 0.001), respectively. RDW ≥ 20.5% at RUX start seems to possibly improve patients' sub-stratification along with anemia and conventional prognostic scoring systems.</p><p><strong>Conclusions: </strong>RDW at RUX start might represent a good indirect measure of MF features and might have prognostic significance for RUX-treated patients affected by MF, aiding in the rapid detection of patients with poor prognosis.</p>","PeriodicalId":44205,"journal":{"name":"Oncology and Therapy","volume":" ","pages":"165-183"},"PeriodicalIF":3.2,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11880497/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143013725","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Niraparib as First-Line Maintenance Therapy in Patients with Stage III Ovarian Cancer and No Visible Residual Disease: AR1ZE Real-World Study.","authors":"Dana M Chase, Maya Hanna, Jonathan T Lim, Tirza Areli Calderón Boyle, Mark Guinter, Madeline Richey, Khilna Patel, Jeanne M Schilder, Jean A Hurteau, Amanda K Golembesky","doi":"10.1007/s40487-024-00318-y","DOIUrl":"10.1007/s40487-024-00318-y","url":null,"abstract":"<p><strong>Introduction: </strong>Niraparib was approved for first-line (1L) maintenance (1LM) treatment of patients with advanced epithelial ovarian cancer (EOC) following the PRIMA/ENGOT-OV26/GOG-3012 (PRIMA) trial. PRIMA was restricted to patients at higher risk of progression (excluded stage III EOC with no visible residual disease [NVRD] after primary cytoreductive surgery [PCS]). This retrospective study evaluated the potential impact of excluding stage III EOC with NVRD from PRIMA by assessing real-world treatment outcomes following 1LM niraparib monotherapy in this patient population.</p><p><strong>Methods: </strong>Data from a US-nationwide electronic health record-derived deidentified database comprised adult patients diagnosed with stage III/IV EOC who received 1L platinum-based chemotherapy and initiated niraparib 1LM monotherapy (01Jan2017-28Feb2023). Patients were classified as PRIMA-like (EOC with higher-risk prognostic factors for disease progression) or stage III disease with NVRD after PCS. Real-world time to next treatment (rwTTNT) and progression-free survival (rwPFS), assessed from the end date of 1L platinum-based chemotherapy, were measured via Kaplan-Meier methods.</p><p><strong>Results: </strong>Among 453 patients who received niraparib 1LM (PRIMA-like cohort, n = 390; stage III NVRD cohort, n = 63), median follow-up from index was 14.9 (interquartile range [IQR], 7.3-25.1) and 18.4 (IQR, 9.3-29.1) months in the PRIMA-like and stage III NVRD cohorts, respectively. Median rwTTNT was significantly longer in the stage III NVRD cohort (22.5 [95% confidence interval (CI), 17.3-not reached] months) than in the PRIMA-like cohort (11.7 [95% CI, 10.8-12.9] months; P < 0.001). Median rwPFS in the stage III NVRD cohort (25.2 [95% CI, 12.6-not reached] months) was more than double that in the PRIMA-like cohort (10.1 [95% CI, 9.1-11.9] months; P < 0.001).</p><p><strong>Conclusions: </strong>In the stage III NVRD cohort, rwTTNT and rwPFS were significantly longer than in the PRIMA-like cohort, consistent with clinical expectation. Results suggest niraparib clinical benefit may have been underestimated in PRIMA because of the exclusion of patients with stage III EOC with NVRD after PCS.</p>","PeriodicalId":44205,"journal":{"name":"Oncology and Therapy","volume":" ","pages":"253-262"},"PeriodicalIF":3.2,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11880480/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142956576","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cost-Effectiveness of Pembrolizumab as First-Line Treatment in Patients with Persistent, Recurrent, or Metastatic Cervical Cancer in the United States.","authors":"Bradley J Monk, Sophie van Mens, Oliver Hale, Jennifer Boer, Frank van Hees, Shilpi Swami, Dominic Muston, Cumhur Tekin, Steve Keefe, Matthew Monberg","doi":"10.1007/s40487-024-00311-5","DOIUrl":"10.1007/s40487-024-00311-5","url":null,"abstract":"<p><strong>Introduction: </strong>First-line treatment of persistent, recurrent, or metastatic (advanced) cervical cancer in patients who have a combined positive score (CPS) ≥ 1 with pembrolizumab + chemotherapy versus standard-of-care chemotherapy provides meaningful improvements in overall survival. We conducted a cost-effectiveness analysis from a US payer perspective. A societal perspective scenario was also considered, including productivity gains.</p><p><strong>Methods: </strong>The cost-effectiveness of pembrolizumab + chemotherapy versus chemotherapy was assessed using a state-transition model comprising the health states \"pre-progression,\" \"post-progression,\" and \"death,\" with a 1-week cycle length and 50-year time horizon. Patient-level KEYNOTE-826 data informed the efficacy, safety, and health-related quality of life of pembrolizumab + chemotherapy versus chemotherapy at first-line and subsequent treatments. Real-world data were sought to cost subsequent treatments according to US clinical practice. Transition probabilities were derived from parametric survival models fit to time-to-progression, progression-free survival, and post-progression survival patient-level KEYNOTE-826 data. Sensitivity analyses explored the impact on outcomes from variables such as bevacizumab use.</p><p><strong>Results: </strong>According to the state-transition model, pembrolizumab + chemotherapy extended mean life expectancy versus chemotherapy from 1.8 to 6.7 life-years. The mean gain of 4.9 life-years/patient was mostly caused by pembrolizumab delaying progression. Total discounted quality-adjusted life-years (QALY) were 5.0 and 1.3 per patient for pembrolizumab + chemotherapy and chemotherapy, respectively (mean gain: 3.7 QALY/patient). Pembrolizumab + chemotherapy had comparable safety outcomes to chemotherapy alone. Total costs incurred were US $320,247 (pembrolizumab + chemotherapy) versus US $105,446 (chemotherapy; mean incremental costs: US $214,801/patient). The incremental cost-effectiveness ratio of pembrolizumab + chemotherapy versus chemotherapy was US $58,446/QALY. Sensitivity analyses showed results were insensitive to bevacizumab use. Including productivity gains led to an incremental cost-effectiveness ratio of US $58,385 per QALY.</p><p><strong>Conclusions: </strong>Our model-based analysis suggests that first-line treatment of pembrolizumab + chemotherapy in advanced cervical cancer with a CPS ≥ 1 offers a substantial clinical benefit over standard-of-care chemotherapy alone and is cost-effective at a willingness-to-pay threshold of US $150,000. The approximate doubling of life-years and QALYs associated with pembrolizumab + chemotherapy represents a step improvement in the treatment of advanced cervical cancer.</p><p><strong>Trial registration: </strong>ClinicalTrials.gov Identification Number: NCT03635567.</p>","PeriodicalId":44205,"journal":{"name":"Oncology and Therapy","volume":" ","pages":"85-98"},"PeriodicalIF":3.2,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11880493/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142584563","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}