Oncology and Therapy最新文献

{"title":"Early Systemic Anti-neoplastic Treatment Post SARS-CoV-2 Infection in Patients with Breast Cancer.","authors":"Naama Halpern, Ben Boursi, Einat Shacham-Shmueli, Einav Nili Gal-Yam, Ofer Margalit, Talia Golan, Tamar Beller, Gal Strauss, Dafna Yahav, Eyal Leshem","doi":"10.1007/s40487-023-00247-2","DOIUrl":"10.1007/s40487-023-00247-2","url":null,"abstract":"<p><strong>Introduction: </strong>It is unclear how soon after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection it is safe to resume systemic anti-neoplastic treatment in patients with cancer. We assessed the risk of admissions or postponed treatment cycle in vaccinated patients with breast cancer receiving early systemic anti-neoplastic treatment following SARS-CoV-2 infection.</p><p><strong>Methods: </strong>This was a retrospective cohort study conducted during Omicron SARS-CoV-2 outbreak in Israel, January-July 2022. SARS-CoV-2 cohort included 30 vaccinated patients with breast cancer with SARS-CoV-2 infection 7-14 days prior to systemic treatment. All patients had resolved symptoms and a negative antigen detection test on the day of treatment. The pre-coronavirus disease 2019 (COVID-19) pandemic cohort consisted of 49 matched patients with breast cancer treated with systemic anti-neoplastic agents during 2019.</p><p><strong>Results: </strong>In 30 vaccinated patients with breast cancer who received systemic anti-neoplastic treatment 7-14 days following SARS-CoV-2 infection, compared with 49 matched patients treated in 2019, the rates of emergency department (ED) visits (13% versus 6%, respectively), hospitalizations (3% versus 4%), next cycle of treatment given per protocol (90% versus 88%), and death (0% versus 0%) were similar.</p><p><strong>Conclusion: </strong>In a cohort of vaccinated patients with breast cancer who received systemic anti-neoplastic treatment 7-14 days after SARS-CoV-2 infection, we did not observe substantially higher rates of ED visits, hospitalizations, or deaths compared with a similar cohort of pre-COVID-19 patients with breast cancer. Most patients received the next planned cycle on time. Early resumption of systemic anti-neoplastic treatment following SARS-CoV-2 infection in vaccinated patients with breast cancer with a negative antigen test at the day of treatment appeared to be safe. Additional data on larger cohorts and other malignancies are needed to support clinical guidelines.</p>","PeriodicalId":44205,"journal":{"name":"Oncology and Therapy","volume":" ","pages":"513-519"},"PeriodicalIF":2.7,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10673789/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49683374","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":"Multiple Real-World Data Sources in a Bayesian Framework to Inform Long-Term Survival Estimates of Mosunetuzumab in Patients with Follicular Lymphoma.","authors":"Javier Sanchez Alvarez, Mahmoud Jaber, Marie-Hélène Blanchet Zumofen","doi":"10.1007/s40487-023-00245-4","DOIUrl":"10.1007/s40487-023-00245-4","url":null,"abstract":"<p><strong>Introduction: </strong>Patients with follicular lymphoma (FL) receiving third-line or later (3L +) therapy have long survival, which can make estimating long-term overall survival (OS) from trial data challenging. The objective of this study was to estimate long-term OS for mosunetuzumab from the GO29781 trial (NCT02500407) using multiple real-world databases (RWDs) in a Bayesian framework.</p><p><strong>Methods: </strong>Seven RWD sources for patients with FL receiving 3L + therapy and the expansion cohort in the GO29781 trial for mosunetuzumab were used. Hazard trends from the RWD sources were analyzed, and disease-wide pointwise OS and its corresponding uncertainty were estimated using Bayesian random-effects meta-analysis from the RWD sources. Pointwise OS obtained was used as an informative prior in Bayesian survival extrapolations to data from patients receiving mosunetuzumab. Results after adjusting for background mortality were compared to equivalent frequentist extrapolations using trial data only.</p><p><strong>Results: </strong>Hazard patterns from RWD sources supported a constant or linearly decreasing hazard. Mean pointwise OS for patients with FL receiving 3L + therapy was estimated at 0.52 (95% credible interval, 0.29-0.85) at 8 years. Bayesian extrapolations for mosunetuzumab produced median survival estimates of 11.6 (6.7-20.7) years to 17.0 (6.4-22.7) years depending on the distribution used, reducing uncertainty by 20% to 46% relative to the frequentist estimation.</p><p><strong>Conclusion: </strong>Multiple RWD sources can be synthesized to augment the credibility of data with short follow-up, long patient survival, and few events to effectively estimate long-term survival and reduce estimated uncertainty. This method can be applied to other indications with similar characteristics.</p><p><strong>Clinical trial registration number and date of registration: </strong>NCT02500407, July 16, 2015.</p>","PeriodicalId":44205,"journal":{"name":"Oncology and Therapy","volume":" ","pages":"495-511"},"PeriodicalIF":2.7,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10673801/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41239683","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":"EGFR Mutations Are Not All the Same: the Importance of Biomarker Testing in Non-small Cell Lung Cancer (NSCLC)-A Podcast Discussion Between Patients and Oncologists.","authors":"Stephen V Liu, Ivy B Elkins, Jill Feldman, Sarah B Goldberg","doi":"10.1007/s40487-023-00242-7","DOIUrl":"10.1007/s40487-023-00242-7","url":null,"abstract":"<p><p>This podcast, for healthcare professionals (HCPs), patients, and patient advocates, is a discussion among a panel of two patients (and co-founders of the patient advocacy group EGFR Resisters, https://egfrcancer.org/ ) and two oncologists. The objective of the podcast is to explain the importance of biomarker testing for patients with EGFR-mutated non-small cell lung cancer. The treatment landscape for EGFR-mutated non-small cell lung cancer is evolving, and biomarker testing has become central to determining the best therapies for individual patients. The panel discusses what biomarkers are, the processes involved in obtaining biomarker testing, how biomarker information is used, and the importance of waiting for biomarker results prior to determining treatment. The panel also discusses patient perspectives on biopsy and biomarker testing and how HCPs can best help guide new patients through this process.</p>","PeriodicalId":44205,"journal":{"name":"Oncology and Therapy","volume":" ","pages":"419-431"},"PeriodicalIF":2.7,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10673799/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41132934","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 Landscape of BRCA Mutations among Egyptian Women with Breast Cancer.","authors":"Hamdy A Azim, Samah A Loutfy, Hatem A Azim, Nermin S Kamal, Nasra F Abdel Fattah, Mostafa H Elberry, Mohamed R Abdelaziz, Marwa Abdelsalam, Madonna Aziz, Kyrillus S Shohdy, Loay Kassem","doi":"10.1007/s40487-023-00240-9","DOIUrl":"10.1007/s40487-023-00240-9","url":null,"abstract":"<p><strong>Background: </strong>Deleterious germline mutations in BRCA1 and BRCA2 genes are associated with a high risk of breast and ovarian cancer. In many developing countries, including Egypt, the prevalence of BRCA1/2 mutations among women with breast cancer (BC) is unknown.</p><p><strong>Aim: </strong>We aimed to determine the prevalence of deleterious germline BRCA mutations in Egyptian patients with breast cancer.</p><p><strong>Methods: </strong>We report the results of a cohort study of 81 Egyptian patients with breast cancer who were tested for germline BRCA1/2 mutations during routine clinical practice, mostly for their young age of presentation, BC subtype, or presence of family history. In addition, we searched five databases to retrieve studies that reported the prevalence of BRCA1/2 mutation status in Egyptian women with BC. A systematic review of the literature was performed, including prospective and retrospective studies.</p><p><strong>Results: </strong>In our patient cohort study, 12 patients (14.8%) were positive for either BRCA1/2 deleterious mutations. Moreover, 13 (16.1%) patients had a variant of unknown significance (VUS) of BRCA1/2 genes. Twelve studies were eligible for the systematic review, including 610 patients. A total of 19 deleterious germline mutations in BRCA1/2 were identified. The pooled prevalence of BRCA1/2 mutations was 40% (95% confidence interval 1-80%).</p><p><strong>Conclusion: </strong>The reported prevalence was highly variable among the small-sized published studies that adopted adequate techniques. In our patient cohort, there was a high incidence of VUS in BRCA1/2 genes. Accordingly, there is an actual demand to conduct a prospective well-designed national study to accurately estimate the prevalence of BRCA1/2 mutations among patients with BC in Egypt.</p>","PeriodicalId":44205,"journal":{"name":"Oncology and Therapy","volume":" ","pages":"445-459"},"PeriodicalIF":2.7,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10673778/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41151989","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":"Genetic Testing in Metastatic Breast Cancer in the USA: A Podcast.","authors":"Reva Basho, Megan-Claire Chase","doi":"10.1007/s40487-023-00243-6","DOIUrl":"10.1007/s40487-023-00243-6","url":null,"abstract":"<p><p>This podcast highlights the importance of genetic testing in patients with metastatic breast cancer, with a specific focus on germline or inherited breast cancer susceptibility gene (BRCA) mutations. In the USA, national guidelines recommend that all patients with recurrent or metastatic breast cancer should be offered genetic testing for germline breast cancer susceptibility gene 1 or 2 (BRCA1 or 2) mutations to identify patients potentially suitable for treatment with a poly(ADP-ribose) polymerase inhibitor. However, a retrospective study indicated that only 43% of patients with hormone receptor-positive/human epidermal growth factor receptor 2-negative advanced breast cancer who may be eligible for genetic testing have undergone germline BRCA1 or 2 testing. Therefore, a large national effort is required to offer genetic testing to more patients with recurrent or metastatic breast cancer. The aim of this podcast is to provide physicians with information to support the early engagement of patients in discussions about genetic testing, and guidance on how to manage patient concerns about the potential implications of testing. Here, a healthcare professional discusses germline genetic testing with a patient advocate and answers questions regarding the importance of testing in patients with metastatic breast cancer. Furthermore, the authors discuss what it means to receive a positive or negative result for a germline BRCA mutation and the impact this may have on the patient and their family members. Overall, the authors emphasize the importance of healthcare professionals providing every patient with metastatic breast cancer with the relevant information about genetic testing so that patients can make informed decisions. Podcast Audio and Infographic available for this article.Podcast Audio and Infographic available for this article.</p>","PeriodicalId":44205,"journal":{"name":"Oncology and Therapy","volume":" ","pages":"433-443"},"PeriodicalIF":2.7,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10673788/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10233020","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":"Recent Advances in Gynecological Malignancies: Focus on ASCO 2023.","authors":"Olga Bodriagova, Rebecca Ann Previs, Lydia Gaba, Abhishek Shankar, Laura Vidal, Kamal S Saini","doi":"10.1007/s40487-023-00244-5","DOIUrl":"10.1007/s40487-023-00244-5","url":null,"abstract":"","PeriodicalId":44205,"journal":{"name":"Oncology and Therapy","volume":" ","pages":"397-409"},"PeriodicalIF":3.2,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10673792/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10317074","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 Treatment Patterns and Outcomes Following First-Line Pertuzumab and Trastuzumab Among Patients with HER2+ Metastatic Breast Cancer.","authors":"Sandhya Mehta, Jipan Xie, Raluca Ionescu-Ittu, Xiaoyu Nie, Winghan J Kwong","doi":"10.1007/s40487-023-00241-8","DOIUrl":"10.1007/s40487-023-00241-8","url":null,"abstract":"<p><strong>Introduction: </strong>Many patients with human epidermal growth factor receptor-2-positive metastatic breast cancer (HER2+ mBC) require subsequent lines of therapy (LOTs) after being treated with pertuzumab and trastuzumab-based regimens in the first line (1L). Although the efficacy of the second-line (2L) therapies has been demonstrated in clinical trials, the real-world effectiveness of these treatments is understudied. This retrospective cohort study assessed the real-world treatment patterns and outcomes for patients with HER2+ mBC following 1L therapy with pertuzumab and trastuzumab-based regimens in the United States (US) during 2015-2019.</p><p><strong>Methods: </strong>Adults with HER2+ mBC in the US who initiated 1L pertuzumab and trastuzumab-based regimens between 01/01/2015 and 09/30/2019 and had ≥ 60 days of follow-up after 1L initiation were identified from the IQVIA Oncology Electronic Medical Records database. The regimens utilized in 2L following 1L pertuzumab and trastuzumab-based regimens were described. Median treatment duration and time to treatment failure were reported for 2L based on Kaplan-Meier analyses.</p><p><strong>Results: </strong>Of the 710 eligible patients who received pertuzumab and trastuzumab-based regimens in 1L (median age: 57.0 years [interquartile range: 48.0-65.0]; median follow-up: 20.3 months; median 1L duration: 15.3 months), 222 (31.3%) initiated 2L. The most common regimens in 2L were ado-trastuzumab emtansine (T-DM1)-based regimens (n = 159 [71.6%]), followed by lapatinib-based (n = 21 [9.5%]) and neratinib-based (n = 18 [8.1%]) regimens. The median treatment duration and time to treatment failure were 5.9 (95% CI: 5.0, 8.7) and 8.6 (7.3, 11.5) months, respectively, among patients initiating 2L, and 5.7 (4.7, 7.8) and 7.9 (6.5, 10.0) months among those receiving 2L T-DM1.</p><p><strong>Conclusions: </strong>Most patients with HER2+ mBC requiring additional treatments after 1L pertuzumab and trastuzumab-based regimens utilized T-DM1 in 2L during 2015-2019. The short median treatment duration and time to treatment failure highlight an unmet need that can potentially be fulfilled by recently approved treatment options.</p>","PeriodicalId":44205,"journal":{"name":"Oncology and Therapy","volume":" ","pages":"481-493"},"PeriodicalIF":2.7,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10673796/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10269590","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":"Shared Decision-Making on Using a CDK4/6 Inhibitor plus an Aromatase Inhibitor for HR+/HER2- Metastatic Breast Cancer: A Podcast.","authors":"Brian Dong, Rita Lusen, Ella Chick, Lisa Kline","doi":"10.1007/s40487-023-00237-4","DOIUrl":"10.1007/s40487-023-00237-4","url":null,"abstract":"<p><p>Shared decision-making involves patients engaging with their physicians to make informed decisions regarding treatment selection, a process that empowers patients and ensures that treatment decisions reflect their individual values and preferences. However, shared decision-making can be challenging to implement for various reasons, including time, staffing, or resource limitations at community practices and differences in patients' cultural backgrounds or health literacy. In this podcast, we discuss how to ensure that individual patients' needs and concerns are addressed, including an overview of different approaches for initial consultations, strategies for tailoring conversations based on a patient's background or health literacy, and trustworthy resources that can help improve patients' understanding. As an illustrative example, we focus on how to implement shared decision-making to address the needs of a patient with hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) metastatic breast cancer who is eligible for combination therapy with a cyclin-dependent kinase 4/6 inhibitor plus an aromatase inhibitor. Overall, this podcast illustrates how shared decision-making is an achievable goal, even in small or underresourced practices, and provides an instructive guide on how to facilitate shared decision-making for patients with HR+/HER2- metastatic breast cancer. Podcast Discussion (MP4 29880 KB) INFOGRAPHIC.</p>","PeriodicalId":44205,"journal":{"name":"Oncology and Therapy","volume":" ","pages":"411-418"},"PeriodicalIF":3.2,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10673755/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41153423","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 Immunomodulatory Effects of Dexamethasone on Neoadjuvant Chemotherapy for Triple-Negative Breast Cancer.","authors":"Kai Conrad Cecil Johnson,&nbsp;Daniel Goldstein,&nbsp;Jasmin Tharakan,&nbsp;Dionisia Quiroga,&nbsp;Mahmoud Kassem,&nbsp;Michael Grimm,&nbsp;Abdul Miah,&nbsp;Craig Vargo,&nbsp;Michael Berger,&nbsp;Preeti Sudheendra,&nbsp;Ashley Pariser,&nbsp;Margaret E Gatti-Mays,&nbsp;Nicole Williams,&nbsp;Daniel Stover,&nbsp;Sagar Sardesai,&nbsp;Robert Wesolowski,&nbsp;Bhuvaneswari Ramaswamy,&nbsp;Gary Tozbikian,&nbsp;Patrick M Schnell,&nbsp;Mathew A Cherian","doi":"10.1007/s40487-023-00235-6","DOIUrl":"https://doi.org/10.1007/s40487-023-00235-6","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Introduction: &lt;/strong&gt;The immunomodulatory impact of corticosteroids and concurrent chemotherapy is poorly understood within triple-negative breast cancer (TNBC). On a biochemical level, steroids have been linked to the signaling of chemotherapy-resistant pathways. However, on a clinical level, steroids play an essential role in chemotherapy tolerance through the prevention of chemotherapy-induced nausea and vomiting (CINV) and hypersensitivity reactions. Given these conflicting roles, we wanted to evaluate this interplay more rigorously in the context of early-stage TNBC.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;We performed a retrospective analysis of patients with operable TNBC who received neoadjuvant chemotherapy (NAC) between January 2012 and November 2018, with the primary goal of examining the dose-dependent relationship between pathological complete response (pCR) rates and corticosteroid use. Secondary endpoints included the impact of steroid dosing on overall survival (OS) and recurrence-free survival (RFS), along with a breakdown in pCR rates based on steroid doses provided during each chemotherapy phase. Further adjusted analyses were performed based on patient age, diabetic status, and anatomical stage. Finally, we explored the relationship between tumor-infiltrating lymphocytes (TILs) seen on tissue samples at baseline and dexamethasone doses in terms of pCR rates.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;In total, of the 174 patients screened within this study period, 116 met full eligibility criteria. Of these eligible patients, all were female, with a median age of 51.5 years (27.0 to 74.0) and a mean body mass index (BMI) of 29.7 [standard deviation (SD) 7.04]. The majority were nondiabetic (80.2%). For cancer stage, 69.8% (n = 81) had stage 2 breast cancer. We found no statistically significant association between pCR rates and dexamethasone use, both in terms of the total dose (p = 0.55) and mean dose per NAC cycle (p = 0.74). Similarly, no difference was noted when adjusting for diabetic status, metformin use, or age at diagnosis, regardless of the total steroid dose provided (p = 0.72) or mean dose per cycle (p = 0.49). No meaningful changes to pCR rate were seen with higher mean or higher total steroid doses during the paclitaxel (T) phase (adjusted p = 0.16 and p = 0.76, respectively) or doxorubicin and cyclophosphamide (AC) phase (adjusted p = 0.83 and p = 0.77, respectively). Furthermore, we found no clinically significant association between dexamethasone dose and either RFS (p = 0.45) or OS (p = 0.89). Of the 56 patients who had available pre-treatment biopsy tissue samples, 27 achieved pCR, with higher TILs at baseline being associated with higher pCR rates, regardless of the mean dexamethasone dose used.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;Our findings demonstrate that dexamethasone has no clinically significant impact on pCR, RFS, or OS when given concurrently with NAC in patients with curative TNBC, regardless of diabeti","PeriodicalId":44205,"journal":{"name":"Oncology and Therapy","volume":"11 3","pages":"361-374"},"PeriodicalIF":2.7,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/6e/86/40487_2023_Article_235.PMC10447758.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10126285","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":"Extrapolation of Survival Data Using a Bayesian Approach: A Case Study Leveraging External Data from Cilta-Cel Therapy in Multiple Myeloma.","authors":"Stephen Palmer, Yi Lin, Thomas G Martin, Sundar Jagannath, Andrzej Jakubowiak, Saad Z Usmani, Nasuh Buyukkaramikli, Hilary Phelps, Rafal Slowik, Feng Pan, Satish Valluri, Lida Pacaud, Graham Jackson","doi":"10.1007/s40487-023-00230-x","DOIUrl":"10.1007/s40487-023-00230-x","url":null,"abstract":"<p><strong>Introduction: </strong>Extrapolating long-term overall survival (OS) from shorter-term clinical trial data is key to health technology assessment in oncology. However, extrapolation using conventional methods is often subject to uncertainty. Using ciltacabtagene autoleucel (cilta-cel), a chimeric antigen receptor T-cell therapy for multiple myeloma, we used a flexible Bayesian approach to demonstrate use of external longer-term data to reduce the uncertainty in long-term extrapolation.</p><p><strong>Methods: </strong>The pivotal CARTITUDE-1 trial (NCT03548207) provided the primary efficacy data for cilta-cel, including a 12-month median follow-up snapshot of OS. Longer-term (48-month median follow-up) survival data from the phase I LEGEND-2 study (NCT03090659) were also available. Twelve-month CARTITUDE-1 OS data were extrapolated in two ways: (1) conventional survival models with standard parametric distributions (uninformed), and (2) Bayesian survival models whose shape prior was informed from 48-month LEGEND-2 data. For validation, extrapolations from 12-month CARTITUDE-1 data were compared with observed 28-month CARTITUDE-1 data.</p><p><strong>Results: </strong>Extrapolations of the 12-month CARTITUDE-1 data using conventional uninformed parametric models were highly variable. Using informative priors from the 48-month LEGEND-2 dataset, the ranges of projected OS at different timepoints were consistently narrower. Area differences between the extrapolation curves and the 28-month CARTITUDE-1 data were generally lower in informed Bayesian models, except for the uninformed log-normal model, which had the lowest difference.</p><p><strong>Conclusions: </strong>Informed Bayesian survival models reduced variation of long-term projections and provided similar projections as the uninformed log-normal model. Bayesian models generated a narrower and more plausible range of OS projections from 12-month data that aligned with observed 28-month data.</p><p><strong>Trial registration: </strong>CARTITUDE-1 ClinicalTrials.gov identifier, NCT03548207. LEGEND-2 ClinicalTrials.gov identifier, NCT03090659, registered retrospectively on 27 March 2017, and ChiCTR-ONH-17012285.</p>","PeriodicalId":44205,"journal":{"name":"Oncology and Therapy","volume":"11 3","pages":"313-326"},"PeriodicalIF":2.7,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/bc/c7/40487_2023_Article_230.PMC10447673.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10425793","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}