Avapritinib versus midostaurin or cladribine in advanced systemic mastocytosis: A retrospective real-world external control study.

Advanced systemic mastocytosis (AdvSM) is a rare myeloid neoplasm associated with poor overall survival (OS). This study (NCT04695431) compared clinical outcomes between patients with AdvSM treated with avapritinib in the Phase 1 EXPLORER (NCT0256198) and Phase 2 PATHFINDER (NCT03580655) trials (N = 176) and patients treated with best available therapy (BAT; N = 141). A multi-center, observational, retrospective chart review study was conducted at six study sites (four European, two American) to collect data from patients with AdvSM who received BAT; these data were pooled with data from EXPLORER and PATHFINDER. Comparisons between outcomes of OS, duration of treatment (DOT), and maximum reduction in serum tryptase were conducted between the treatment cohorts, with adjustment for key covariates. The results indicated that the avapritinib cohort had significantly better survival (adjusted hazard ratio (HR) (95% confidence interval (CI)): 0.48 (0.29, 0.79); p = 0.004) and significantly longer DOT (HR: 0.36 (0.26, 0.51); p < 0.001) compared to the BAT cohort. Additionally, the mean difference in percentage maximum reduction in serum tryptase levels was 60.3% greater in the avapritinib cohort (95% CI: −72.8, −47.9; p < 0.001). With no randomized controlled trials comparing avapritinib to BAT, these data offer crucial insights into the improved efficacy of avapritinib for the treatment of AdvSM.

MM-233 Evaluation of the Comparative Effectiveness of In-Class Transition (iCT) to All-Oral Ixazomib-Lenalidomide-Dexamethasone (IRd) After Bortezomib (V)-Based Induction Therapy vs Patients Who Continued to Receive Parenteral V-Based Therapy in Newly Diagnosed Multiple Myeloma (NDMM)

Outcomes of Rituximab and Bendamustine Induction Regimen VS Cytarabine-Based Induction for Patients with Mantle Cell Lymphoma

Redefining Prognosis in Patients with KIT D816V Positive Advanced Systemic Mastocytosis on KIT Inhibitors

The association of adjuvant chemotherapy (AC) with survival in the general population of patients with resected biliary tract cancer (BTC) remains controversial. As such, the role of this treatment in the treatment of older adult patients (aged ≥70 years) needs to be evaluated. To describe the patterns of use of AC and compare survival outcomes of AC and observation in older adult patients following resection of BTC. This retrospective cohort study included 8091 older adult patients with resected BTC with data available in the National Cancer Database from January 1, 2004, to December 31, 2019. Patients were divided into 2 cohorts: AC and observation. The AC cohort was subdivided into single-agent and multiagent AC treatment. Adjuvant chemotherapy vs observation following BTC resection. The primary outcome was overall survival (OS) of patients who received AC compared with observation following resection of BTC as evaluated using Kaplan-Meier estimates and multivariable Cox proportional hazards regression models. Inverse probability of treatment weighting and propensity score matching were performed to address indication bias. Between 2004 and 2019, of 8091 older adult patients with resected BTC identified (median [range] age, 77 [70-90] years; 5136 women [63.5%]; 2955 men [36.5%]), only one-third (2632 [32.5%]) received AC. There was an increase in the use of AC across the study period from 20.7% (n = 495) in 2004 to 2009 to 41.2% (n = 856) in 2016 to 2019. Age 80 years or older (odds ratio, 0.29; 95% CI, 0.25-0.33; P < .001) and gallbladder primary site (odds ratio, 0.71; 95% CI, 0.61-0.83; P < .001) were associated with a lower odds of AC. Following inverse probability of treatment weighting, as a composite, AC was not associated with improved survival (median OS, 20.5 months; 95% CI, 19.2-21.7 months) compared with observation (median OS, 19.0 months; 95% CI, 18.1-20.3 months). A longer median OS was associated with single-agent AC (21.5 months; 95% CI, 19.9-24.0 months) but not multiagent AC (19.1 months; 95% CI, 17.5-21.1 months) compared with observation (median OS, 17.3 months; 95% CI, 16.1-18.4 months). This improvement in OS with single-agent AC was not apparent on multivariable analysis (hazard ratio [HR], 0.97; 95% CI, 0.89-1.05; P = .44). However, age at diagnosis of 80 years or older (HR, 1.35; 95% CI, 1.28-1.42; P < .001) and treatment at nonacademic centers (HR, 1.14; 95% CI, 1.07-1.20, P < .001) were associated with worse OS. In this cohort study of older adult patients, AC was not associated with an improvement in survival compared with observation following BTC resection. These findings suggest the need for further study of AC for older adult patients who may benefit after curative intent surgery for BTC.

Adjustment for imbalances in baseline characteristics in the MAGNITUDE phase 3 study confirms the clinical benefit of niraparib in combination with abiraterone acetate plus prednisone in patients with metastatic prostate cancer

1111 Background: Cyclin-dependent kinase 4/6 inhibitor in combination with endocrine therapy (CDK4/6i) is the current standard of care in first line (1L) treatment for hormone receptor–positive and human epidermal growth factor receptor 2-negative (HR+/HER2–) metastatic breast cancer (mBC). Comparative effectiveness evidence assessing overall survival (OS) outcomes are limited, particularly in older pts. Our primary objective was to compare OS in Medicare pts treated with 1L PAL + AI versus AI alone in the current SEER dataset. Methods: We conducted a retrospective analysis of HR+/HER2–mBC pts using the SEER-Medicare database. Medicare-enrolled pts aged ≥65 years diagnosed with de novo HR+/HER2– mBC between February 1, 2015, and December 31, 2019 were included. Pts were followed from the start of 1L therapy line until death, Medicare disenrollment, enrollment in a health maintenance organization plan, or the end of available study follow-up (December 31, 2020), whichever came first. Stabilized inverse probability of treatment weighting (sIPTW) was the primary method used to balance patient characteristics at baseline, with propensity score matching (PSM) and multivariable CPH regression as sensitivity analyses. Median OS and the hazard ratio (HR) were estimated using the weighted Kaplan-Meier (KM) method and the weighted Cox proportional hazard (CPH) regression model, respectively. Results: Of 779 included pts, 296 received PAL+AI and 483 received AI alone. Median follow-up was 23.9 months for the PAL+AI arm and 18.2 months for the AI alone arm. After sIPTW adjustment, median OS was 37.6 months (95% CI=34.8-42.0) for PAL+AI vs 25.5 months (95% CI=22.0-28.9) for AI alone (HR=0.73, 95% CI=0.59-0.91). Results from the PSM and CPH regression analyses were consistent with the primary analysis. Key patient characteristics are presented (Table). Conclusions: This comparative effectiveness study showed that PAL+AI was associated with significantly prolonged OS vs AI alone in the 1L treatment of older pts with de novo HR+/HER2- mBC treated in US clinical practice using the SEER-Medicare database. Our results add to the body of evidence on the survival benefit of PAL+AI in this population. [Table: see text]

Molecular Quantification of Tissue Mast Cell Burden in Systemic Mastocytosis: A New Approach for Diagnostics and Prognostication

BackgroundColorectal cancer is one of the tumors with the highest morbidity and mortality rates in China and the world. Regorafenib is a targeted drug for standard third-line treatment of metastatic colorectal cancer (mCRC). Regorafenib monotherapy has shown certain efficacy in the elderly population, but more robust evidence is needed. The aim of this study was to evaluate the dosing characteristics, prognosis, and safety of regorafenib monotherapy in elderly Chinese patients with mCRC.MethodsThis retrospective study comprised elderly patients (aged ≥60 years) with mCRC who received regorafenib monotherapy as a third-line or above treatment in 10 hospitals from August 2017 to June 2020. We analyzed the association between different dosing regimens and prognosis. The primary endpoint was overall survival (OS), and other endpoints included progression-free survival (PFS) and adverse events (AEs).ResultsIn total, 203 patients were included in the analysis. The median PFS was 3.88 months [95% confidence interval (CI): 3.48–5.65], and the median OS was 10.1 months (95% CI: 8.94–12.1). There was no significant difference in the survival curves between the different dosage groups. The multivariate Cox analysis showed a significant benefit in OS in the high final daily dose group (120–160 mg/day) [hazard ratio (HR): 0.45, 95% CI: 0.25–0.84, P=0.01], which was further confirmed by the propensity score matching (PSM) and inverse probability of treatment weighting (IPTW) analysis. No significant association was found between the initial daily dose and prognosis. Nor was any significant association found between PFS and drug dosage. Subsequently, an age subgroup analysis was conducted using 70 years as the cut-off value. In those aged <70 years, the application of higher final doses (120–160 mg/day) was significantly associated with the prolongation of OS compared to a final dose of 80 mg/day [HR (95% CI): 0.38 (0.16–0.91), P=0.03], and the prolongation of OS was predominantly observed in the 120 mg/day dose group [HR (95% CI): 0.24 (0.09–0.67), P=0.006]. Besides, we observed a statistically insignificant increase in the incidence of AEs in the higher dose group compared to the lower dose group.ConclusionsRegorafenib monotherapy was shown to be efficacious in the elderly population, but further evidence is needed for guidance. Based on our multicenter real-world investigation, the final daily dose was significantly associated with OS. For those aged <70 years, maintaining the final dose at 120 mg/day may have prognostic advantages. The suggested medication protocol requires validation through comprehensive clinical trials.

Patients with triple class exposed (TCE), relapsed and refractory (RR) multiple myeloma (MM) have limited treatment options and poor prognosis. Elranatamab, a bispecific BCMA-targeted antibody, is an investigational treatment for RRMM with demonstrated efficacy and safety in MagnetisMM-3, a single-arm, multi-centre, phase-2 study. This study aimed to characterise outcomes for real world TCE RRMM patients and to estimate the treatment effect of elranatamab compared to treatments available in routine clinical care for TCE RRMM in the NHS. A retrospective, observational, external control arm (ECA) study combining participants from a single arm, multi-centre phase 2 study, MagnetisMM-3, receiving elranatamab to compare patient characteristics and median survival using a comparator cohort of TCE RRMM patients treated with real world regimens in five UK centres between 2015 and 2023. Both naive and adjusted treatment effect estimates for progression free survival (PFS) and overall survival (OS) were obtained using inverse probability of treatment weighted (IPTW) Cox proportional hazards models and differences in restricted mean survival time (dRMST). Quantitative bias analysis was used to assess the robustness of effect estimates to unmeasured confounding. From a total of 5,535 patients identified with a diagnosis of MM, 81 were identified as eligible for inclusion in the ECA. A total of 13 different regimens were recorded as being initiated from the real world RRMM at index date, the most common regimen was pomalidomide + dexamethasone (48.15%). Clinical outcomes in the ECA were poor (median PFS 3.71 months [95% confidence interval (CI) 2.73-4.73], median OS 11.00 months [8.02-18.10]). In unadjusted analyses the elranatamab cohort had significant improvements in PFS (dRMST 6.95 months [4.08-9.61]) and OS (Hazard Ratio (HR) 0.66 [0.45-0.96]). Adjusted analyses showed similar effects for PFS (dRMST 6.45 [3.05-9.45]) but were equivocal for OS (HR 0.75 [0.46-1.26]). This study provides recent real world evidence of poor outcomes in TCE RRMM in the UK. PFS was longer among patients who received elranatamab compared with treatments for TCE RRMM in routine UK clinical practice.

Although the National Comprehensive Cancer Network (NCCN) guidelines recommend use of lymph node dissection (LND) in patients with pancreatic neuroendocrine tumors (pNETs) > 2cm, there is limited evidence to support the association between use of LND and overall survival (OS). Patients with resected pNETs were identified in the National Cancer Database (2004-2014). The inverse probability of treatment weighting (IPTW) method was used to reduce the selection bias. IPTW-adjusted Kaplan-Meier curves and Cox proportional hazards models were used to compare OS of patients in different treatment groups. A total of 2664 patients diagnosed met the study entry criteria. Of these, 2132 patients (80.6%) received LND, with a median of nine nodes removed. Positive nodes were identified in 28.0% of patients who underwent LND. IPTW-adjusted Kaplan-Meier analysis showed that median OS was similar between the LND and LND-omitted groups (152.8 vs. 147.3months; p = 0.61). In IPTW-adjusted Cox proportional hazards regression analysis, LND was not associated with an OS benefit (hazard ratio [HR] 1.15, 95% confidence interval [CI] 0.94-1.42; p = 0.18). The results were consistent across subgroups stratified by clinical T and N stages. Among patients with lymph node metastasis, the number of removed nodes (NRN) above the median was not associated with an improved OS (HR 0.82, 95% CI 0.60-1.13; p = 0.22). LND had no additional therapeutic benefit among patients undergoing resection for pNETs. The present findings should be considered when managing patients with resectable pNETs.

Effective Control of Advance Systemic Mastocytosis with Avapritinib: Mutational Analysis from the Explorer Clinical Study

Black women suffer from a persistent disparity in breast cancer mortality after controlling for prognostic and sociodemographic factors, suggesting that differential receipt or efficacy of treatment may contribute to their poorer outcomes. Black women are more likely to experience delays in diagnostic workup and initiation of treatment, but it is not known whether i) timeliness of subsequent care is also impacted, and ii) racial disparities in time to treatment initiation and completion persist among black and white women with comparable clinical and sociodemographic characteristics. The Carolina Breast Cancer Study Phase III is a large population-based cohort of North Carolina women newly diagnosed with breast cancer. This study was restricted to black and white women undergoing surgery for the treatment of nonmetastatic disease. We investigated mean differences in the distribution of time from diagnosis to earliest surgery, chemotherapy, or radiation treatment (treatment initiation) and once started, time to treatment completion (treatment duration) by race. Only treatment-oriented surgeries excluding biopsies were included in this analysis, and last or definitive surgery was defined as the final treatment-oriented surgery occurring prior to recurrence and within 18 months of diagnosis. Cumulative incidence curves were used to graphically examine the distributions of time to treatment initiation and treatment duration, and general linear models were used to estimate crude and adjusted mean differences in time to treatment initiation and duration between black and white women. We also conducted stratified analyses to examine racial disparities by age and stage at diagnosis, hormone receptor (HR) and human epidermal growth factor receptor 2 (HER2) positivity, treatment pathway (surgery only, surgery plus chemotherapy, surgery plus radiation, or all three modalities), marital status, education level, income, and insurance type. A total of 1,328 black and 1,331 white women met study inclusion criteria. Overall, black women had an average of 3.68 additional days to treatment initiation and 34.26 days longer treatment duration than white women, for 37.94 days longer total treatment time (95% confidence interval (CI): 34.21-41.67). Adjustment for clinical and sociodemographic factors resulted in a greater estimated mean difference in time to initiate treatment (4.04 days, 95% CI: 3.08-5.00), while it attenuated the mean difference in treatment duration towards the null (9.07 days, 95% CI: 6.82-11.32). Black women experienced significantly longer time to initiate treatment and treatment duration in nearly every stratum of clinical or sociodemographic factor examined. Black women with stage II or III tumors had significantly longer time to initiate treatment than white women (4.50 and 7.84 days, respectively), and after starting treatment, treatment duration was approximately 25 days longer for black women with stage I and II disease. Black women undergoing radiation and/or chemotherapy had longer time to initiate treatment and significantly longer treatment durations. Having a college education or higher or being insured through Medicaid were associated with the greatest mean differences in time to treatment initiation comparing black and white women. Younger age at diagnosis, HR+ or HER2- disease, being unmarried, having less than a high school education, and being uninsured were associated with the greatest mean differences in treatment duration by race. Overall, black women experienced longer intervals between diagnosis and treatment initiation and greater treatment durations after controlling for clinical and sociodemographic factors. Racial disparities were more pronounced in examination of treatment duration, suggesting that interventions to improve care coordination and timeliness should be targeted at high-risk groups. Citation Format: Sophie E. Mayer, Melissa Troester, Stephanie B. Wheeler, Andrew Olshan, Lisa A. Carey, Jessica Tse, Katherine E. Reeder-Hayes. Temporal patterns of breast cancer treatment initiation and completion among black and white women in the Carolina Breast Cancer Study [abstract]. In: Proceedings of the Tenth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2017 Sep 25-28; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2018;27(7 Suppl):Abstract nr PR11.

The present study aimed to compare the pattern of distant recurrence between patients with non-metastatic rectal cancer treated with pre-operative (OP) and those treated with post-operative (post-OP) chemoradiotherapy (CRT). A total of 631 patients with newly diagnosed non-metastatic rectal cancer who had received pre-OP or post-OP CRT with curative intent surgery between August 2008 and April 2015 were identified. Inverse probability of treatment weighting (IPTW) was performed to account for baseline differences between the two arms. Overall, 449 and 182 patients were treated with pre-OP and post-OP CRT, respectively. Sex, tumor location, clinical tumor stage, CRT regimen and adjuvant chemotherapy regimen were significantly different between the two arms. The median follow-up duration was 55.4 months (range, 53.7-57.1). The 5-year distant recurrence-free survival (RFS) rates and 5-year overall survival (OS) rates were not significantly different between the pre-OP and post-OP CRT arms (RFS, 67.5 vs. 71.6%, P=0.595 and OS, 81.9 vs. 77.0%, P=0.449), and no difference was observed in the distant recurrence patterns. Following IPTW, there was still no difference in distant RFS (pre-OP vs. post-OP CRT; hazard ratio (HR)=0.62; P=0.911), but pre-OP CRT was significantly associated with lower peritoneal recurrence (pre-OP vs. post-OP CRT; HR, 0.13; P=0.032). In addition, there was no significant difference in OS between the two arms (pre-OP vs. post-OP CRT; HR, 0.85; P=0.665). In conclusion, although distant RFS was not significantly different between the two arms, pre-OP CRT was significantly associated with a lower risk of peritoneal recurrence than post-OP CRT in patients non-metastatic rectal cancer.

To examine, for the first time, whether cyclosporine intake has an early isolated effect on the optic nerve. This observational case series consisted of 192 eyes of 98 patients treated with cyclosporine. Patient age and duration and dosage of cyclosporine were recorded, and visual acuity, optic nerve function, visual fields, and visual evoked potential (VEP) were tested. Fundus examination was also performed. Patients with glaucoma, vascular retinopathies, and deep amblyopia were excluded. Mean patient age was 46years, average duration of treatment was 6years, and median dosage of cyclosporine was 200mg daily. VEP was tested in 73 patients (142 eyes) and yielded a delayed P100 wave in 9 (12.32%) (14 eyes). Among these 9 patients, abnormal findings were also noted on the Ishihara colour test in 42.86% of the eyes, and on the visual field test in 64.3% of the eyes. Abnormal VEP showed a significant correlation (p < 0.05) with older age (> 46years) and a non-significant correlation with longer duration of treatment. Higher abnormal VEP potential was not correlated with higher cyclosporine dose, and there was no correlation between abnormal VEP and blood level of cyclosporine. Optic neuropathy was significantly associated with older age in cyclosporine-treated patients. A correlation between optic neuropathy with longer duration of cyclosporine treatment was noted but was not statistically significant. We suggest that tests of optic nerve function, including VEP, be a part of the follow-up of patients receiving cyclosporine.