No abstract
Objectives Peripheral T-cell lymphomas (PTCLs) are a rare and aggressive type of non-Hodgkin lymphoma (NHL) associated with a poor prognosis. Common frontline (1L) regimens include brentuximab vedotin plus cyclophosphamide, doxorubicin, and prednisone (A+CHP), and cyclophosphamide, doxorubicin, vincristine, and prednisone with or without the addition of etoposide (CHOP and CHOEP, respectively). Based on the 5-year update of the ECHELON-2 trial, patients with previously untreated CD30-expressing PTCL on A+CHP continued to demonstrate clinically meaningful improvements in progression-free survival (PFS) and overall survival (OS) compared with CHOP. Our objective was to estimate the future number of patients alive and progression free with A+CHP over 10-years, based on the 5-year follow-up results from ECHELON-2. Methods An oncology simulation model, from the United States perspective, was developed with a 1-month cycle length that estimates population-level outcomes of PTCL patients based on disease incidence, treatment patterns, PFS, and OS of commonly used regimens for PTCL. Incidence of PTCL, 19.26 cases per 100,000 persons, was derived using Surveillance, Epidemiology and End Results (SEER) estimates for NHL in 2020 and the estimated proportion of PTCL cases (~4%) within the NHL category, provided by the Lymphoma Research Foundation. To populate the base case model, treatment patterns following 1L utilization of CHOP (65%) and CHOEP (35%) were varied over time and compared to A+CHP (40%). The model also includes a portion of patients in remission in 1L who are eligible to receive transplant therapy. Additional model inputs were derived from: 1) ECHELON-2, with 5-year PFS rates of 51.4% (95% CI 42.8, 59.4) for A+CHP, 43.0% (95% CI 35.8, 50.0) for CHOP, and OS HR 0.72 (95% 0.53, 0.99); 2) published literature to inform PFS for consolidation and subsequent lines of therapy; and 3) expert clinicians' opinion on commonly used regimens for relapsed/refractory PTCL (included in the model were brentuximab vedotin, romidepsin, pralatrexate, ifosfamide in combination with carboplatin and etoposide [ICE], and gemcitabine-based regimens). Annual prevalence of patients living progression-free with PTCL in the 1L setting with each prescribed scenario was estimated for 10 years (year 2031) with and without the availability of A+CHP. Results The cumulative number of patients with newly diagnosed PTCL between 2026 and 2031 was estimated at 8,020. The number of patients alive and progression-free based on 1L treatment was estimated at 6,304 in a scenario without A+CHP and 7,414 with A+CHP (Δ+1,110, 17.6% increase) in 2031. It was also estimated that 1,203 patients would progress to second-line treatment with CHOP vs 1,119 patients with 1L A+CHP (Δ-84, 7.0% decrease) in 2031. Conclusions The durable and significant improvements in PFS and OS of A+CHP vs CHOP in the 5-year follow-up data from ECHELON-2 estimated an increase in the number of 1L PTCL patients who remain progression free and alive for greater than 10 years. This improvement in outcomes may translate into an increased prevalence of PTCL patients, reflecting an increased number of patients in remission and options to undergo transplant therapy when necessary. Disclosures Burke: Adaptive Biotechnologies: Consultancy; AstraZeneca: Consultancy; Roche/Genentech: Consultancy; SeaGen: Consultancy, Speakers Bureau; Beigene: Consultancy, Speakers Bureau; Epizyme: Consultancy; AbbVie: Consultancy; Bristol Myers Squibb: Consultancy; X4 Pharmaceuticals: Consultancy; Kymera: Consultancy; MorphoSys: Consultancy; Kura: Consultancy; Verastem: Consultancy. Yu: Seagen, Inc: Current Employment, Current equity holder in publicly-traded company. Bloudek: Seagen, Inc: Consultancy. Liu: Seagen, Inc: Current Employment, Current equity holder in publicly-traded company. Fanale: Seagen, Inc: Current Employment, Current equity holder in publicly-traded company. Phillips: Genentech: Membership on an entity's Board of Directors or advisory committees, Research Funding; AbbVie: Consultancy, Research Funding; BMS: Consultancy, Research Funding; Bayer: Consultancy, Research Funding; AstraZeneca: Consultancy; Incyte: Consultancy, Other: received travel expenses from Incyte, Research Funding; ADCT, BeiGene, Bristol Myers Squibb, Cardinal Health, Incyte, Karyopharm, Morphosys, Pharmacyclics, Seattle Genetics: Consultancy.
We demonstrate a new model framework as an innovative approach to more accurately estimate and project prevalence and survival outcomes in oncology. Methods: We developed an oncology simulation model (OSM) framework that offers a customizable, dynamic simulation model to generate population-level, country-specific estimates of prevalence, incidence of patients progressing from earlier stages (progressionbased incidence), and survival in oncology. The framework, a continuous dynamic Markov cohort model, was implemented in Microsoft Excel. The simulation runs continuously through a prespecified calendar time range. Time-varying incidence, treatment patterns, treatment rates, and treatment pathways are specified by year to account for guideline-directed changes in standard of care and real-world trends, as well as newly approved clinical treatments. Patient cohorts transition between defined health states, with transitions informed by progression-free survival and overall survival as reported in published literature. Results: Model outputs include point prevalence and period prevalence, with options for highly granular prevalence predictions by disease stage, treatment pathway, or time of diagnosis. As a use case, we leveraged the OSM framework to estimate the prevalence of bladder cancer in the United States. Conclusion:The OSM is a robust model that builds upon existing modeling practices to offer an innovative, transparent approach in estimating prevalence, progression-based incidence, and survival for oncologic conditions. The OSM combines and extends the capabilities of other common health-economic modeling approaches to provide a detailed and comprehensive modeling framework to estimate prevalence in oncology using simulation modeling and to assess the impacts of new treatments on prevalence over time.
Objectives Doxorubicin, bleomycin, vinblastine and dacarbazine (ABVD) is the most common frontline (1L) regimen for patients with stage III or IV classical Hodgkin lymphoma (cHL), but about 30% of patients with stage III or IV cHL have refractory or relapsed disease after ABVD treatment. Based on the 5-year update of the ECHELON-1 trial, patients on 1L brentuximab vedotin, doxorubicin, vinblastine and dacarbazine (A+AVD) continued to demonstrate a robust and durable progression-free survival (PFS) improvement vs ABVD with a 32% reduction in the risk of progression or death (HR=0.681, nominal P=0.002). Our objective was to estimate the future number of patients with cHL who are alive and progression-free over 10-years with 1L A+AVD, based on the 5-year follow-up results from ECHELON-1. Methods An oncology simulation model, from the United States perspective, was developed with a 1-month cycle length that estimates population-level outcomes based on annual prevalence of cHL, considering disease incidence, treatment patterns, PFS, and overall survival of commonly used treatment regimens for stage III or IV cHL. Incidence of cHL was derived from the 2019 Surveillance, Epidemiology, and End Results (SEER) Program, assuming 95% of HL is classical of which 41% is stage III or IV. To populate the base case model, treatment patterns following 1L use of ABVD (64.5%) and positron emission tomography (PET)-adapted therapy (35.5%) were varied over time and compared to A+AVD (24%). For every model cycle, patients who experienced disease progression on 1L therapy discontinued therapy and transitioned to second-line (salvage) therapy. The transition from second-line therapy to transplant is also included in the model based on patient eligibility. Model inputs were informed by 1) real-world treatment utilization; 2) treatment-specific clinical trial data, including ECHELON-1 with 5-year PFS rates of 75.3% for ABVD (95% CI: 70.0, 85.0) and 82.2% for A+AVD (95% CI: 71.7, 78.5); and 3) expert clinicians' opinions. Annual prevalence of patients living progression-free with cHL in the 1L setting with each prescribing scenario was estimated for 10 years (year 2031) with and without the availability of A+AVD. Results The annual number of newly diagnosed patients with stage III or IV cHL at 10 years in 2031 was estimated at 3,586. The number of patients alive and progression-free in the 1L setting was 19,494 without A+AVD and 19,660 with A+AVD (Δ+166, 0.85% increase) in 2031. Overall, for every 100 patients prescribed A+AVD, it was predicted that an additional 6.5 patients per year achieved at least 5 years PFS and 4.2 to 4.7 fewer patients per year required a stem cell transplant (SCT), based on the 70% to 80% of eligible patient proceeding to SCT, respectively. Conclusions The durable PFS improvement of A+AVD vs ABVD in the 5-year follow-up data from ECHELON-1 resulted in increasing the number of patients with stage III or IV cHL who remain progression free for greater than 10 years and reducing future SCTs, based on this oncology simulation model for cHL. The significant improvement in PFS observed in the 5-year ECHELON-1 trial may translate to fewer patients with cHL developing primary refractory or relapsed disease and reduce the need for additional therapies including SCT. Disclosures Phillips: Genentech: Membership on an entity's Board of Directors or advisory committees, Research Funding; BMS: Consultancy, Research Funding; Bayer: Consultancy, Research Funding; Incyte: Consultancy, Other: received travel expenses from Incyte, Research Funding; ADCT, BeiGene, Bristol Myers Squibb, Cardinal Health, Incyte, Karyopharm, Morphosys, Pharmacyclics, Seattle Genetics: Consultancy; AbbVie: Consultancy, Research Funding; AstraZeneca: Consultancy. Migliaccio-Walle: Seagen, Inc: Consultancy. Yu: Seagen, Inc: Current Employment, Current equity holder in publicly-traded company. Bloudek: Seagen, Inc: Consultancy. Liu: Seagen, Inc: Current Employment, Current equity holder in publicly-traded company. Fanale: Seagen, Inc: Current Employment, Current equity holder in publicly-traded company. Burke: Beigene: Consultancy, Speakers Bureau; Verastem: Consultancy; Kymera: Consultancy; Bristol Myers Squibb: Consultancy; Adaptive Biotechnologies: Consultancy; MorphoSys: Consultancy; AstraZeneca: Consultancy; Roche/Genentech: Consultancy; Kura: Consultancy; Epizyme: Consultancy; X4 Pharmaceuticals: Consultancy; SeaGen: Consultancy, Speakers Bureau; AbbVie: Consultancy.
4575 Background: First-line (1L) maintenance avelumab (maintA) in patients with advanced urothelial carcinoma (aUC) prolonged overall survival (OS) in the JAVELIN Bladder 100 trial. JAVELIN measured OS from the initiation of maintA among a subgroup of the overall aUC 1L treated population, including only patients who did not progress with 1L platinum-based therapy (PBT) and remained progression free during a 4-10 week treatment-free interval following completion of 1L PBT. As such, patients who progressed on or immediately following PBT were not included in the trial. To address this, we used disease modeling to estimate maintA OS measured from initiation of 1L PBT to align maintA OS with the common initiation point to benchmark with other 1L clinical trials. Methods: We developed a simulated cohort to estimate OS from initiation of 1L PBT in all aUC patients including those who received maintA. Eligibility for maintA (PBT progressed vs not progressed) was assessed at 5.6 months post-initiation of 1L PBT, accounting for 6 PBT cycles and a nominal 6-week treatment-free interval. Median OS of 14.3 months from the 1L PBT arm of a recent 1L trial, KEYNOTE-361, was used to represent the OS of the simulated cohort of 1L aUC patients. The simulated cohort was stratified by eligibility for maintA. Among the 1L treated population, 57% were projected to be progression-free and eligible for maintA based on progression-free survival (PFS) from KEYNOTE-361. Among those eligible, 85% were assumed to receive maintA based on expert clinical input. OS of maintA eligible patients was 21.4 months from JAVELIN. Our disease model estimated OS among a maintA ineligible simulated cohort, which was combined with the maintA eligible cohort to yield an estimated OS in the overall aUC population measured from initiation of 1L PBT. Results: Approximately 50% of the 1L modeled population receive maintA (i.e., 57% eligible x 85% treated). Our approach estimated a median OS of 9.9 months for the maintA ineligible cohort and 27.0 months for the maintA eligible cohort. Combined, the estimated median OS with maintA, measured from initiation of 1L PBT, in all 1L-treated aUC patients was 15.8 months (vs 14.3 months with PBT only in 1L). Conclusions: MaintA improves OS for eligible patients, however our simulation model suggests a significant proportion of patients will not receive MaintA. The estimated OS of 15.8 months for the population-level impact of maintA, accounting for patients ineligible for 1L maintA, demonstrates remaining unmet need in the overall 1L aUC population.
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