Clinical Outcomes In Pts Research Articles

Association of enfortumab vedotin (EV) toxicity with baseline parameters and clinical outcomes in patients (pts) with metastatic urothelial carcinoma (mUC).

e16585 Background: EV is an antibody-drug conjugate approved for the treatment of mUC. Toxicities of special interest with EV are neuropathy, rash, and hyperglycemia. While it has been reported that EV-related skin toxicity may be associated with better responses to EV, the relationship of EV-related adverse events (AEs) with clinical outcomes is still unclear. The aim of this study is to investigate the association of EV-related toxicity and clinical outcomes among pts with mUC. Methods: We retrospectively reviewed demographic, clinical and laboratory data from pts with mUC who were treated with > 1 dose of EV at Dana-Farber Cancer Institute. AEs were graded per the CTCAE V5.0. A multivariable Cox regression analysis was performed to analyze overall survival (OS) and the occurrence of AEs while accounting for age, sex, and baseline peripheral neuropathy (BPN). A landmark analysis was performed to evaluate the association of toxicity occurrence and clinical outcomes, accounting for guarantee-time bias. Results: Our cohort included 54 pts with a median age of 72 years, of which 72.2% (n = 39) were male. Median follow-up was 18.6 months. Neuropathy was the most common AE occurring in 66.7% (n = 36) pts with 7.4% (n = 4) grade 3-4. Skin toxicity occurred in 57.4% (n = 31) pts with 3.7% (n = 2) grade 3-4. There were no recorded grade 5 AEs. Worse baseline Eastern Cooperative Oncology Group Performance Status (ECOG-PS) was associated with the development of more AEs (HR = 2.8; 95% CI = 1.2-6.3; p = 0.01). Decreased baseline hemoglobin (Hb) was associated with more EV-related neuropathy (1/HR = 1.25; 95% CI = 1.1-1.4; p = 0.01) and higher neuropathy grade (1/HR = 1.7; 95% CI = 1.1-2.5; p = 0.01). Moreover, pts who have previously received immune checkpoint inhibitors (ICI) were more likely to develop EV-related rash (HR = 5.4; 95% CI = 1.1-26.2; p = 0.03; Table 1). Overall, 30 deaths were observed, and median OS was 13.3 months (95% CI = 9.5-NA). A landmark analysis at 2 weeks of therapy (marking the final infusion of the 1st cycle of EV therapy) showed that in 16 pts who developed early skin toxicity, OS was improved vs. 38 pts who did not develop early skin toxicity (HR = 0.4; 95% CI = 0.2-0.9; p = 0.04). Conclusions: To our knowledge, this is the first study to investigate the association of EV-related AEs and clinical outcomes of pts with mUC using a landmark analysis. ECOG-PS and baseline Hb may be predictors of EV-related AEs. The incidence of early skin toxicity may be associated with improved OS. [Table: see text]

Outcomes of patients (pts) with de novo metastatic hormone-sensitive prostate cancer (mHSPC) who progressed to metastatic castration-resistant prostate cancer (mCRPC): A post-hoc analysis of the TRUMPET registry.

e17085 Background: Significant lack of treatment (Tx) intensification is seen in clinical practice for pts with mHSPC until progression to mCRPC. The TRUMPET registry enabled a post-hoc analysis of clinical outcomes in pts with mCRPC, initially diagnosed with de novo mHSPC vs nmHSPC. Methods: TRUMPET, a prospective, observational study of US pts with CRPC, enrolled male adults (03/2015-09/2018) who began first or second-line Tx for M0/M1 CRPC. For this post hoc, pts with M1 CRPC at enrollment initially diagnosed with de novo mHSPC (clinical TNM1 stage) were compared to M1 CRPC pts initially diagnosed with nmHSPC (clinical TNM0 stage). Clinical outcomes (radiographic progression-free survival [rPFS], prostate specific antigen [PSA] progression, time to opiate initiation [OI], mortality) were analysed with Kaplan–Meier and Cox proportional hazards models. An exploratory subanalysis investigated outcomes in de novo mHSPC pts who received Tx intensification (docetaxel or abiraterone) with androgen-deprivation therapy (ADT) as primary Tx prior to mCRPC vs pts who did not. Results: M1 CRPC pts initially diagnosed with de novo mHSPC (n = 199) or nmHSPC (n = 254) were included; median age: 70.0 vs 73.0 years, duration from initial PC diagnosis to baseline mCRPC visit: 1.62 vs 6.72 years, PSA at PC diagnosis: 113.1 vs 10.1 ng/mL, Gleason score: 9.0 vs 8.0, respectively. In the de novo mHSPC and nmHSPC groups, initial CRPC Tx was chemotherapy in 9.0% vs 5.9% of pts, novel hormonal therapy (enzalutamide or abiraterone) in 55.3% vs 59.1%, immunotherapy in 35.2% vs 42.9%, respectively. No differences were seen in rPFS or PSA progression (table). The de novo mHSPC group showed a trend toward shorter time to OI and significantly increased risk of mortality (37%) with 6.6 months shorter median survival vs nmHSPC. The subanalysis included 44 (22.1%) de novo mHSPC pts who received Tx intensification with ADT at initial diagnosis. A trend towards improved survival was seen in the Tx-intensified vs nonintensified subgroup (median time to death [95%CI]; 47.7 months [22.18, NE] vs 37.3 months [28.35, 43.01]). Conclusions: At mCRPC diagnosis, pts with de novo mHSPC have significantly higher mortality risk than pts with nmHSPC, indicating a need to delay progression of de novo mHSPC to mCRPC. The trend for improved survival benefit in pts with Tx-intensified de novo mHSPC further underlines the need for early Tx intensification. [Table: see text]

Hematologic and transfusion outcomes in patients (pts) with lower-risk myelodysplastic syndromes (LR-MDS) receiving luspatercept: Real-world assessment in the community practice setting.

7057 Background: Erythropoiesis-stimulating agents (ESAs) are used as first-line (1L) treatment (tx) for the management of symptomatic anemia in LR-MDS. Luspatercept is approved for pts with LR-MDS with ring sideroblasts (RS) who experience ESA failure and are transfusion dependent. We assessed clinical outcomes of pts with LR-MDS with RS, or MDS/myeloproliferative neoplasms with RS and thrombocytosis, treated with luspatercept in US community practices. Methods: This retrospective, observational cohort study used physician-abstracted chart data from community oncology clinics and included adults diagnosed with LR-MDS (including Very low- to Intermediate-risk IPSS-R status) on/after Jan 1, 2015 who received luspatercept for ≥ 3 months (mos) with ≥ 3 mos of follow-up. Transfusion burden (TB) was defined by number of sessions (ses) received in the 8 weeks (wks) prior to luspatercept tx (baseline) and the lowest number for any consecutive period ≥ 8 wks during wks 1–24 of tx: transfusion independent (TI); low TB (LTB), 1–3 ses; and moderate TB (MTB), 4–5 ses. Results: Of 253 pts, 219 (87%) had 1 tx prior to luspatercept tx and 31 (12%) received ≥ 2. ESAs were used as 1L tx in 210 pts (83%). Median follow-up was 5.7 mos. The most common reason for discontinuing initial MDS tx among patients who received ≥ 1 tx prior to luspatercept was lack of anemia improvement (133/250). At baseline, 21 (8%) pts were TI, 208 (82%) had LTB, and 24 (10%) MTB. Median duration of luspatercept tx was 10.8 mos. During wks 1–24, 20/21 (95%) pts remained TI and 201/232 (87%) pts with LTB/MTB at baseline achieved TI for ≥ 8 wks. The Table shows changes in median hemoglobin (Hb), absolute neutrophil count (ANC), and platelet (plt) count. Conclusions: Most pts with LR-MDS received 1L ESAs and over half discontinued the first tx prior to luspatercept due to lack of anemia improvement, highlighting the need for alternative options to improve clinical outcomes. Consistent with data from the MEDALIST trial, 87% of pts with LTB/MTB who received luspatercept achieved TI for ≥ 8 wks, supporting its clinical benefit in routine clinical practice. [Table: see text]

Real-world assessment of treatment effectiveness in patients with advanced non-small cell lung cancer (aNSCLC) with MET exon 14 skipping (METex14).

e21112 Background: Capmatinib is approved for patients (pts) with advanced stage (a)NSCLC harboring METex14. However, there is limited data on capmatinib activity in comparison to other approved therapies. We assessed real-world (rw) clinical outcomes of pts with aNSCLC with METex14 who initiated treatment with capmatinib, immunotherapy (IO), or chemotherapy (CT) regimens. Methods: In a retrospective chart review, data were abstracted by a sample of oncologists invited nation-wide in the US who randomly selected prespecified numbers of charts, with larger sampling targets for capmatinib and IO therapies. Eligible pts were aged ≥18 years, had stage ≥IIIB NSCLC and METex14; received first-line (1L) systemic therapy after 1 January 2017 with follow up of ≥6 months after starting 1L therapy (except death) as of the data abstraction date; and did not receive MET inhibitors other than capmatinib. Clinical outcomes included best overall real world response rate (rwORR), progression-free survival (rwPFS), overall survival (OS), and time to treatment discontinuation (TTD). RwORR was assessed using rw-RECIST guided by RECIST 1.1 criteria or physician documentation. All measures were descriptively analyzed. Time-to-event outcomes were assessed per line of therapy via Kaplan-Meier methods. Results: In total, 287 eligible pts were identified. Median age was 63.3 years, 71% were male, 41% were non-White, and 49.5% were treated in community settings. 15 pts had brain metastasis at diagnosis. Pts who received 1L capmatinib had higher rwORR and longer rwPFS, OS, and TTD than pts who received 1L IO mono or CT alone or in combination (Table 1). Pts treated with second-line (2L) capmatinib had higher rwORR than other treatments but was a smaller pt population. Conclusions: Our analysis suggests that capmatinib in aNSCLC with METex14 yields numerically better clinical outcomes than IO or CT alone or in combination. These findings support use of capmatinib in this setting and may inform clinical decision making in routine practice. [Table: see text]

Prognostic impact of depth of response (DpR) and early tumour shrinkage (ETS) in patients (pts) with BRAF V600E mutated (mut) metastatic colorectal cancer (mCRC) receiving targeted therapy (TT) as second-line treatment.

3568 Background: Encorafenib and cetuximab (EC) is the standard of care for pre-treated patients (pts) with BRAF V600E mut mCRC. DpR and ETS previously showed a strong correlation with survival outcomes in mCRC pts receiving 1st-line therapy. We assessed these tumour dynamic response parameters and their association with clinical outcome in pts with BRAF V600E mut mCRC treated with TT in second-line. Methods: Patients treated in a real-life setting with EC or EC plus binimetinib (ECB) in 20 Italian centres were included. Pts with measurable disease and at least one available disease reassessment by CT scan were eligible. Pts experiencing disease progression as best response (i.e. primary resistant) were not evaluable for DpR and ETS. Associations between DpR and ETS and progression free survival (PFS) and overall survival (OS) were tested by univariate and multivariate models. Results: 105 pts were included: 89 (85%) and 16 (15%) pts were treated with EC and ECB, respectively. Median PFS and OS were 5.2 and 10.3 mos, respectively. Twenty-nine pts (28%) were primary resistant, while 76 (72%) pts achieved disease control (51 [48%] and 25 [24%] pts had SD or CR/PR, respectively). Among baseline characteristics, the presence of peritoneal metastases was a predictor of primary resistance (p = 0.04). Among pts evaluable for response parameters (n = 76), median DpR was 15% and ETS occurred in 28 pts (37%). Mucinous histology was associated with a significantly lower magnitude of DpR (p = 0.005) and a lower rate of ETS (p = 0.002). A significant association between DpR and PFS was observed, both as a dichotomous ( ie, ≥ or < median value) and continuous variable in univariate and multivariate analyses. Also RECIST response correlated with PFS in the two models (table). DpR was associated with OS in the univariate analyses, but this was not confirmed in the multivariate models (table). No correlation between ETS and survival, either as a dichotomous ( ie, ≥ or < 20%) or a continuous variable, was observed. Conclusions: Having a DpR of at least 15% predicts longer PFS and OS in patients with BRAF V600E mut mCRC receiving TT as second-line treatment. An independent cohort of pts treated with second-line chemotherapy +/- antiangiogenic is under investigation as control group. [Table: see text]

Real-world outcomes in patients (pts) with metastatic triple-negative breast cancer (mTNBC) treated with sacituzumab govitecan (SG) in 2L+ in the United States (US).

e18879 Background: Pts with mTNBC have poor prognosis and limited treatment options. SG is an anti—Trop-2 antibody-drug conjugate approved in multiple countries for pts with mTNBC who received at least 1 prior systemic therapy and in the US for pts with pretreated HR+/HER2- mBC. In the pivotal phase 3 ASCENT study (NCT02574455), SG demonstrated superior efficacy over single-agent chemotherapy and a manageable safety profile in pts with mTNBCardia A, et al. NEJM. 2021). This study is, to our knowledge, the first to describe real-world treatment patterns and dosing with SG and its impact on clinical outcomes in pts with mTNBC in the US. Methods: This retrospective, observational cohort study used the ConcertAI Patient360™ dataset with additional curated electronic medical record data from the US. Pts (≥18 years) diagnosed with mTNBC as defined according to the current American Society of Clinical Oncology/College of American Pathologists guidelines (HER2 IHC0, 1, or 2/ISH-negative; ER/PR <1%) and initiating treatment with SG (index date) in 2L+ from April 2020 to May 2022 were included. Real-world clinical outcomes with SG and use patterns were assessed. Kaplan-Meier method was used to determine real-world overall survival (rwOS). Results: In total, 230 pts met the eligibility criteria and were included for analysis. All pts were female; 64% were White and 26% Black; median age was 60 years (IQR, 49-69); 71% of pts presented with ECOG performance status ≤1; 71% had visceral metastases and 7% had brain metastases at baseline. The median time from mBC diagnosis to SG treatment initiation was 11.8 months (IQR, 7.6-19.2). Most pts (66%) were treated in a community setting; 34%, 28%, 19%, and 20% of pts were treated with SG in the 2L, 3L, 4L, and 5L+ setting, respectively. Between 2020-2022, there was a trend in the distribution of SG use shifting to earlier line settings, see Table. Median starting dose was 10 mg/kg (IQR, 9.8-10.1). Median follow-up duration was 7.2 months (IQR, 3.9-11.1). Median rwOS (95% CI) from index date was 10 months (8.3-11.1) among all pts. Median rwOS (95% CI) was 13.9 months (9.79-not estimable) and 8.4 months (7.7-10.3) among pts treated with SG in 2L and in 3L+ setting, respectively. Analyses on real-world patterns of SG use are ongoing and additional results will be provided. Conclusions: Pts who were treated with SG in routine clinical practice were older, more ethnically diverse, and presented with worse performance status than pts enrolled in the ASCENT trial but demonstrated a similar survival benefit. The proportion of pts treated with 2L SG increased from 2020 to 2022, reflecting an expected dynamic of post approval drug uptake in routine practice. [Table: see text]

190MO Association of 18-Gene expression profile (GEP) with clinical outcomes in patients with metastatic triple-negative breast cancer (mTNBC) treated with pembrolizumab (Pembro) or chemotherapy (Chemo) in KEYNOTE-119

In the phase III, randomized, open-label KEYNOTE-119 (NCT02555657) study, second- or third-line treatment with pembro monotherapy did not significantly improve OS vs single-agent chemo treatment of physician’s choice (TPC) in patients (pts) with mTNBC, although the pembro treatment effect increased with increasing PD-L1 enrichment. In this exploratory analysis, we evaluated the association of T-cell-inflamed gene expression profile (GEP) with clinical outcomes from KEYNOTE-119. Pts with centrally confirmed mTNBC, ECOG PS ≤1, and 1-2 prior systemic treatments for metastatic breast cancer were randomized 1:1 to pembro 200 mg Q3W for up to 35 cycles or TPC (capecitabine, eribulin, gemcitabine, or vinorelbine) per local guidelines. Tumor RNA profiling was conducted on the RNA-seq platform (Illumina, San Diego, CA). Association of GEP with clinical outcomes was evaluated by logistic regression (best objective response [BOR] per RECIST v1.1) and Cox proportional hazards models (PFS and OS) with baseline adjustment for ECOG PS; 95% CIs for BOR were estimated using the Clopper and Pearson method. As of April 11, 2019, GEP data for 333 pts (pembro, n=177; TPC, n=156) were available for analysis. GEP was significantly associated with improved BOR, PFS, and OS in pts treated with pembro but not TPC (Table). HR for OS was 0.77 (95% CI, 0.58–1.04) in pts with GEP non-low (≥1st tertile) and 1.72 (1.15–2.55) in pts with GEP low (<1st tertile). No association was seen between BRCA/HRD status and treatment response. These findings suggest a positive association between GEP and clinical outcomes in pts with mTNBC who are treated with pembro, with a more favorable treatment effect in the GEP-enriched population. Results may help inform future analyses of outcomes by biomarker status in this population.

Abstract CT077: Association of tumor mutational burden (TMB) and clinical outcomes with tislelizumab versus chemotherapy in esophageal cell carcinoma (ESCC) from RATIONALE-302

Abstract Background: Programmed cell death protein 1 (PD-1) inhibitors are approved as second-line (2L) therapy for patients (pts) with ESCC. TMB is a predictive biomarker of response to immune checkpoint blockade in multiple cancers, but its role in ESCC is unclear. Here, we retrospectively investigated the association between TMB and clinical outcomes in the phase 3 RATIONALE-302 study of anti-PD-1 antibody tislelizumab (TIS) vs investigator-chosen chemotherapy (ICC) as 2L treatment for advanced unresectable/metastatic ESCC (NCT03430843). Methods: Genomic profiling was assessed on tumor tissues collected at baseline using BurningRock OncoScreen Plus 520 NGS panel to determine TMB status. Median progression-free survival (PFS) and overall survival (OS) were calculated using the Kaplan-Meier method. Objective response rate (ORR) was calculated using the binomial exact method. Cox model was applied to assess the effect of TMB on survival outcomes. Hazard ratio (HR) and 95% confidence interval (CI) for OS and PFS in TMB subgroups were estimated. Results: Of 512 pts enrolled, 209 had evaluable tumor samples (TIS, n=105; ICC, n=104). Using the widely used cutoff of 10 mutations per megabase (mut/Mb), numerically higher ORR and survival benefit with TIS over ICC were observed in the high TMB (TMB-H) vs the low TMB (TMB-L) subgroup (Table). The predictive effect of TMB on survival outcomes was not significant (interaction p-value = 0.0537 for PFS, 0.5374 for OS); however, the effect became significant using the increased cutoff of 12 mut/Mb (TMB-H prevalence = 16.7%; interaction p-value = 0.0267 for PFS, 0.0175 for OS). Conclusions: TMB status may play a role in predicting clinical outcomes in pts with advanced ESCC treated with TIS versus ICC, especially when a higher TMB cutoff is chosen. These findings need further prospective validation. Acknowledgments: This study was sponsored by BeiGene, Ltd. Medical writing support, under the direction of the authors, was provided by Sophie Cook, PhD, of Ashfield MedComms, an Inizio company, and was funded by BeiGene, Ltd. Table. Clinical outcomes by TMB status (cutoff 10 mut/Mb) TMB status TMB-H TMB-L Treatment TIS ICC TIS ICC n (% in TMB BEP, N=209) 27 (12.9) 31 (14.8) 78 (37.3) 73 (34.9) ORR, % (95% CI) 33.3 (16.5, 54.0) 6.5 (0.8, 21.4) 16.7 (9.2, 26.8) 17.8 (9.8, 28.5) Median PFS, months (95% CI) 2.4 (1.4, 5.5) 2.3 (1.3, 2.9) 1.4 (1.3, 2.7) 2.7 (1.5, 3.3) PFS HR (95% CI) 0.52 (0.28, 0.97) 1.06 (0.73, 1.53) Interaction p-value 0.0537 Median OS, months (95% CI) 6.1 (4.2, 18.6) 4.7 (3.4, 7.0) 8.6 (4.6, 11.8) 7.0 (4.6, 8.6) OS HR (95% CI) 0.58 (0.32, 1.04) 0.72 (0.50, 1.03) Interaction p-value 0.5374 TMB-adjusted OS HR (95% CI) 0.68 (0.5, 0.92) BEP, biomarker evaluable population; CI, confidence interval; HR, hazard ratio; ICC, investigator chosen chemotherapy; OS, overall survival; PFS, progression-free survival; ORR, objective response rate; TIS, tislelizumab; TMB-H, high tumor mutational burden; TMB-L, low tumor mutational burden; TMB-adjusted OS HR, overall HR adjusted for the impact of TMB on OS Citation Format: Lin Shen, Yongqian Shu, Kuaile Zhao, Taroh Satoh, Zhendong Chen, Eric Van Cutsem, Guohua Yu, Jun Wu, Chih-Hung Hsu, Sung Bae Kim, Wenting Du, Yang Shi, Ruiqi Huang, Qiao Li, Jingwen Shi, Yun Zhang, Kato Ken. Association of tumor mutational burden (TMB) and clinical outcomes with tislelizumab versus chemotherapy in esophageal cell carcinoma (ESCC) from RATIONALE-302 [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 2 (Clinical Trials and Late-Breaking Research); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(8_Suppl):Abstract nr CT077.

Real-world clinical outcomes of patients with localized prostate cancer (LPC) treated with external beam radiation therapy (EBRT).

330 Background: Patients (pts) with localized prostate cancer (LPC) or locally advanced prostate cancer (PC) have several treatment options, including external beam radiation therapy (EBRT) and radical prostatectomy, which can be curative in some pts. However, limited real-world evidence exists on the long-term clinical outcomes of these pts, particularly those with high-risk LPC (HRLPC). This study examines real-world clinical outcomes for HRLPC and low/intermediate risk LPC (LIRLPC) pts treated with EBRT in the US. Methods: A retrospective study using Surveillance, Epidemiology, and End Results (SEER)-Medicare linked registry-claims data from 2012−2019 included LPC pts aged ≥65 treated with EBRT as initial definitive therapy. Baseline demographic and clinical characteristics were summarized for HRLPC and LIRLPC pts. Clinical outcomes of interest (overall survival, metastasis-free survival [MFS] and time to initiation of advanced PC treatment) were compared using Kaplan-Meier (KM) and Cox proportional hazards (PH) models. Results: Of 11,127 LPC pts treated with EBRT within 6 months of LPC diagnosis, ~40% (n=4,414) were HRLPC and ~60% (N=6,713) were LIRLPC. Patient characteristics for both groups appeared similar, with mean age at EBRT initiation &gt;70 years, 86% white, and mean follow-up time &gt;40 months. ADT was used with EBRT in 78% HRLPC and 34% LIRLPC. Median (IQR) duration of ADT therapy (via KM analysis) was 9.9 (5.8, 21.5) months for HRLPC and 7.2 (5.3, 9.8) months for LIRLPC. A higher proportion of HRLPC vs LIRLPC pts experienced metastasis, death, and progression to advanced PC therapies (medians were not reached). Unadjusted Cox PH survival analyses showed higher risk of mortality, metastasis, and advanced PC therapy use for HRLPC vs LIRLPC pts. Conclusions: This real-world study of clinical outcomes in pts with HRLPC and LIRLPC treated with EBRT suggested substantial additional disease burden in pts with HRLPC and highlights the need for additional strategies and treatments to improve clinical outcomes in pts with HRLPC. [Table: see text]

Evaluation of clinical benefit of sacituzumab govitecan (SG) following enfortumab vedotin (EV) in advanced urothelial cancer (UC): Real-world experience.

523 Background: In the TROPHY study, 8.8% of the 113 patients (pts) were enrolled post EV treatment, with ORR to SG of 30% in that small subset. Response to SG post EV in real world populations has not been previously reported. SG has accelerated FDA approval for treatment refractory UC, with ORR of 27% in the TROPHY-U-01 trial. SG was developed contemporaneously to EV, which like SG, is also an antibody-drug conjugate (ADC), composed of an alternate antibody linker and chemotherapy payload. The EV ORR is 40-52% in single agent studies, and outcomes following SG to EV have not been reported. Optimal therapy sequence for advanced UC, concerns for cross resistance between ADCs and other targeted therapies, and biomarker selection for agents is underexplored. We describe clinical outcomes in pts with advanced UC treated with SG following EV. Methods: In this retrospective study of pts with UC treated with SG after progression on EV at the Johns Hopkins Greenberg Bladder Cancer Institute between November 2020 and October 2022, 17 pts were identified. Fourteen received SG in the next line following EV, 3 had other interval therapies between EV and SG. Response was determined by physician assessed RECIST criteria. All pts were response evaluable for prior EV. Three pts died shortly after C1 SG without imaging and were not response evaluable. Results: In our cohort 8 (47%) pts were female, 3 (17.6%) were African-American and 14 (82.4%) were Caucasian. Mean age was 68.3 years. Primary location was bladder for 9 (52.9%) pts and UTUC for 7 (41.2%). One (5.9%) patient had disease in both primary sites. Two (11.8%) pts had lymph node only disease, 8 (47.1%) had metastatic disease in the lungs, 6 (35.3%) in the liver and 1(5.9%) in bone. Mean number of EV cycles was 5.9 (1-12) and PFS was 5.9 months. Best EV response was CR in 1 (5.9%), PR in 10 (58.8%), SD in 2 (11.8%) and PD in 4 (23.5%) pts. SG was dose reduced in C1 with prophylactic growth factor support in 13/17 pts in this heavily pretreated population. Mean number of SG cycles was 3.8 (1.5-6). Best SG response for the 14 response evaluable pts was PR for 3 (21.4%) pts and SD for 3 (21.4%), for a clinical benefit (CR+PR+SD) rate of 42.8%. Eight pts had best response of PD (57.1%). SG discontinuation was for PD in 8 pts (57.1%) and 4 (28.6%) due to functional decline or toxicity. One patient had PD to SG in C2 but received 3 additional cycles due to therapeutic benefit. Three (21.4%) pts continue SG, after 6 cycles with PR and after 5 and 4 cycles with SD. For 14 response evaluable pts, the PFS on SG was 2.4 months. Conclusions: In this retrospective analysis, pts with advanced UC and PD following EV had meaningful clinical benefit rate to SG of 42.8% despite dose reduction in this small late line cohort. Defining optimal sequence of ADCs and other therapies in UC remains an unmet need. Updated data will be presented.

The impact of homologous recombination repair (HRR) gene mutation status on treatment (tx) patterns and clinical outcomes among patients (pts) with metastatic castration-resistant prostate cancer (mCRPC) in the United States (US).

97 Background: There is a paucity of evidence that evaluates the impact of HRR mutation status on clinical outcomes in pts with mCRPC. This study assessed the real-world (rw) progression-free survival (rwPFS) based on HRR mutation status (HRR mutated [HRRm]), HRR wild type (HRRwt) among pts with mCRPC in the US. Methods: Data from pts with mCRPC initiating first line (1L) tx between 2016 and 2019 and known HRR status based on germline or tumor testing were retrospectively abstracted from medical charts by physicians in the US from 2021–2022. Pt demographic and clinical characteristics were summarized descriptively across subgroups by HRR status (HRRm vs HRRwt). HRRm was defined as a mutation in at least 1 of 12 genes of interest ( BRCA1, BRCA2, PALB2, ATM, ATR, CHEK2, FANCA, MLH1, MRE11A, NBN, RAD51C, CDK12), regardless of test type. RwPFS on 1L mCRPC tx was compared among pts with HRRm vs HRRwt genes and BRCA1/2 HRRm vs HRRwt genes using the Kaplan–Meier method and log-rank test. Results: A total of 80 physicians contributed data from charts of 130 pts (N=51 HRRm and N=79 HRRwt). Among pts with HRRm genes, 34 (67%) were positive for BRCA1 or BRCA2 mutations. In pts with known timing of testing (n=88), 33% were tested prior to initiation of 1L therapy and 67% after initiation of 1L therapy. In the 1L setting, novel hormonal therapy (NHT) was utilized in 29% of pts with HRRm vs 58% with HRRwt genes (P&lt;0.01). Chemotherapy was utilized in 43% of pts with HRRm vs 34% with HRRwt genes (P=0.40); docetaxel was the most common agent, utilized in 26% vs 27% of pts with HRRm vs HRRwt genes. Median rwPFS on 1L tx was 19 months (95% CI: 11–NE) vs 31 months (95% CI: 23–NE), P=0.11, for pts with HRRm vs HRRwt genes, respectively. RwPFS for pts with BRCA1/2 HRRm genes (N=34) vs HRRwt genes was 19 months (95% CI: 11–NE) vs 31 months (95% CI: 23–NE), P=0.17. Conclusions: In this rw study, genomic testing was performed frequently in later stages of metastatic disease. Pts with HRRm genes had numerically shorter rwPFS on 1L standard therapies compared with HRRwt pts. While unmet needs exist to optimize mCRPC txs and prolong disease progression irrespective of HRRm mutation status, further studies are warranted to further elucidate the prognostic role of HRRm and BRCA1/2 mutations on clinical outcomes.

Safety and efficacy from the phase 1 SURPASS trial of ADP-A2M4CD8, a next-generation T-cell receptor T-cell therapy, in patients with advanced esophageal, esophagogastric junction, or gastric cancer.

349 Background: ADP-A2M4CD8 is a specific peptide enhanced affinity receptor mixed CD4+ and CD8+ T-cell therapy targeting the cancer testis antigen MAGE-A4 and modified with addition of a CD8α co-receptor designed to provide additional functionality to CD4+ T-cells. ADP-A2M4CD8 has demonstrated a favorable benefit to risk profile in the Phase 1 SURPASS trial (NCT04044859) in HLA A*02–eligible patients (pts) with unresectable or metastatic tumors positive for MAGE-A4 (Hong DS, et al. E-poster 540P: ESMO 2021; Virtual). Here we report updated clinical outcomes in pts with esophageal, esophagogastric junction (EGJ), or gastric cancer. Methods: SURPASS is a first-in-human trial consisting of a modified 3+3 dose-escalation design and an expansion cohort. Autologous T-cells are obtained by leukapheresis, transduced with a self-inactivating lentiviral vector expressing the MAGE-A4-specific T-cell receptor and the CD8α co-receptor, and infused back to the pts as ADP-A2M4CD8 following lymphodepleting chemotherapy. Primary and secondary objectives are safety and anti-tumor activity, respectively. Results: As September 6, 2022, 13 pts (11 male, 2 female) with esophageal (3), EGJ (8), and gastric cancer (2) received ADP-A2M4CD8 (range: 1.02–9.9x109 transduced T-cells). All pts had adenocarcinoma, median age was 55 years (range: 31–71), median MAGE-A4 expression H-score was 245 (range: 160–300), and pts received median of 2 lines of prior therapy (range 1–5). Adverse events (AEs) were consistent with those typically associated with lymphodepleting chemotherapy, cellular therapy, and/or disease. One pt had a Grade 5 (fatal) AE of pancytopenia. Overall response rate per RECIST v1.1 by investigator review was 15% (2 partial response [PR]). Disease control rate was 77% (2 PR+8 stable disease). This trial is ongoing, and additional data will be presented. Conclusions: Results indicate an acceptable benefit to risk profile and encouraging anti-tumor activity of ADP-A2M4CD8. An additional treatment cohort has been included in the updated SURPASS trial protocol to evaluate ADP-A2M4CD8 combined with nivolumab. A Phase 2, open-label trial in advanced esophageal and EGJ cancers has been initiated (SURPASS-2; NCT04752358). Clinical trial information: NCT04044859 .

A phase II study of atezolizumab (ATEZO) and bevacizumab (BEV) in combination with Y90 TARE in patients (pts) with hepatocellular carcinoma (HCC): Y90+/- BEAT.

TPS629 Background: The anti–PD-L1 antibody ATEZO prevents PD-L1 from interacting with PD-1 and B7.1, thus reinvigorating antitumor T cell activity. Anti-VEGF BEV can increase dendritic cell maturation, enhance T cell infiltration, and reduce myeloid-derived suppressor cells and regulatory T-cells in tumors. This combination has been FDA approved for first-line treatment of advanced HCC based on the IMbrave150 study. On the other hand, locoregional radiotherapy (e.g., Y90 TARE) enhances the diversity of the intratumoral T cell receptor repertoire. It is the standard of care for pts with intermediate-stage HCC (iHCC). Based on preclinical and clinical data, we hypothesize that the combination of Y90 TARE, BEV, and ATEZO induces synergistic tumor-killing. Methods: This is an open-label, multicenter, randomized phase II study of Y90 TARE and BEV plus ATEZO compared with Y90 TARE alone in pts with unresectable IHCC (NCT04541173). The primary study objective is to assess and compare the progression-free survival (PFS) (per mRECIST 1.1) of pts in each arm. The main secondary objective is to determine the safety and tolerability (CTCAE v5) of TARE combined with ATEZO and BEV in pts with HCC. Exploratory objectives are to assess the role of the immunoscore and PD-L1 expression levels in the prediction of improved clinical outcome in pts receiving Y-90 TARE and BEV plus ATEZO; the composition of tumor-infiltrating immune cell subtypes in predicting response to a chosen therapy; how Y90 therapy affects the proportion of antigen-presenting cells in the tumor; and symptoms experienced by pts receiving TARE and BEV plus ATEZO treatment, using patient-reported outcomes. Eligible pts have either HCC that is not amenable to surgical resection, confirmed by pathology review, or at least BCLC stage B HCC outside of downstaging criteria. Other standard eligibility criteria apply. Pts must have a pretreatment liver biopsy taken and then be randomized 1:1 to TARE (Arm A) or TARE followed by ATEZO and BEV (Arm B). Pts will have TARE mapping during week (wk) 1 and TARE treatment during wk 2. In Arm B, pts will start BEV plus ATEZO 4 wks (±1 wk) after TARE treatment. Pts will have abdominal MRI or CT scans every 12 weeks, CT scans of the chest every 24 wks. Disease progression will be captured by both RECIST 1.1 and mRECIST. We plan to assess the safety of TARE with BEV and ATEZO in the first 10 pts randomized to Arm B for two cycles. If there are no Grade ≥ 3 unexpected toxicities possibly, probably or definitely related to combined TARE plus BEV plus ATEZO, the study will continue to accrue 128 pts in total. Pts will continue study treatment (Arm B) for a total of 24 months from initiation of TARE or until intolerable toxicity or disease progression occur, whichever is earlier. Clinical trial information: NCT04541173 .

P630 Upadacitinib Improves Clinical Outcomes in Patients with Moderate to Severely Active Crohn’s Disease Irrespective of Previous Failure to Respond to Biologics or Conventional Therapies

Abstract Background Upadacitinib (UPA), an oral, selective Janus kinase inhibitor, demonstrated significantly greater efficacy compared with placebo (PBO) in patients (pts) with moderately to severely active Crohn’s disease (CD) in phase 3 multicentre, double-blind, PBO-controlled induction U-EXCEL and U-EXCEED, and maintenance U-ENDURE trials.1-3 This analysis compared clinical outcomes in pts treated with UPA vs PBO once daily (QD) among pts without or with a history of biologic failure. Methods Eligible pts with an average daily very soft/liquid stool frequency (SF) ≥4 and/or abdominal pain score (APS) ≥2, plus a Simple Endoscopic Score for CD (excluding the narrowing component) ≥6 (≥4 for pts with isolated ileal disease) were randomized (2:1) to UPA 45 mg (UPA45) or PBO in U-EXCEL and U-EXCEED. Induction responders (≥30% decrease in average daily very soft/liquid SF and/or APS, neither worse than baseline) to 12-week (wk) UPA45 were re-randomized 1:1:1 for maintenance to UPA 15 mg (UPA15), UPA 30 mg (UPA30) or PBO QD in U-ENDURE. Clinical remission, response (CR-100), and maintenance of clinical remission, along with adverse events (AEs) were assessed through maintenance wk 52. Results Baseline demographics/characteristics were similar for all treatment groups; pts with prior biologic failure were 71.5% PBO and 72.0% UPA45 in induction and 76.4% PBO, 73.4% UPA15 and 75.6% UPA30 in maintenance. Among pts without/with biologic failure history, those treated with UPA45 exhibited higher rates for clinical remission at wk 12 (CDAI: UPA45 54.1%/40.5% vs PBO 39.4%/19.4%; SF/APS: UPA45 54.0%/42.2% vs PBO 28.3%/14.1%, Fig. 1A). Similar results were observed at wk 52 with UPA15 and UPA30 vs PBO (Fig. 1B). Irrespective of biologic failure status, a higher proportion of patients on either UPA dose maintained clinical remission from maintenance wk 0 to wk 52 (Fig. 1C). Higher proportions of pts with prior biologic failure achieved CR-100 with UPA45 vs PBO at wk 12 (53.2% vs 26. 9%); at wk 52 differences from PBO were found for either UPA dose in pts without or with prior biologic failure (Fig. 1D). Serious AEs and serious infections were similar across treatment groups (Tables 1-2). No tuberculosis or adjudicated cardiovascular events were reported. Malignancy, opportunistic infections, thrombotic events, and gastrointestinal perforations were infrequent (&amp;lt;1.0% or 10 E/100PY). Conclusion All upadacitinib doses achieved greater clinical efficacy than placebo during induction and maintenance periods, irrespective of patient prior exposure to biologic therapy, with an acceptable safety profile.

Prophylactic Corticosteroid Use with Axicabtagene Ciloleucel (axi-cel) in Patients with Relapsed/Refractory Large B-Cell Lymphoma (R/R LBCL): Real-World Practice Patterns and Outcomes

Introduction: To minimize toxicities associated with axi-cel, several exploratory safety management cohorts were added to the ZUMA-1 study. In cohort 6 (n = 40), prophylactic (ppx) corticosteroid (CS) use beginning on day 0 was assessed as an intervention strategy to decrease grade ≥ 3 cytokine release syndrome (CRS)/ immune effector cell associated neurotoxicity (ICANS). No grade ≥3 CRS was observed and Grade ≥3 ICANS was observed in 13% of cases without any difference in objective response rate (ORR) or complete response rate (CR) when compared to cohorts that did not use ppx treatment. Based on these findings, the FDA approved an update to the prescribing information for axi-cel to include use of ppx CS across all approved indications in January 2022. However, ppx CS use is not a mandatory standard treatment and has not been universally adopted. We sought to establish the real-world practice patterns of ppx CS use and clinical outcomes. Methods: To assess real-world practice patterns of ppx CS use with axi-cel for R/R LBCL, we sent a 5-question survey to 22 centers across the US axi-cel certified treatment centers. Next, to assess the clinical outcomes of pts receiving ppx CS, we conducted a multicenter retrospective review of pts with R/R LBCL undergoing axi-cel since the FDA approval for prophylactic indication. Baseline characteristics were compared between the no ppx vs. the ppx CS groups. Axi-cel-related toxicities CRS and ICANS were graded based on ASTCT 2019 guidelines. Updated data will be presented at the meeting with more pts and longer follow up. Results: Of the 22 centers, 17 (77%) responded to the questionnaire, with 11/22 (50%) using ppx CS (figure 1). Six centers that had not adopted the ppx steroids cited various reasons such as limited data on efficacy, presence of clinical trial using ppx CS, and unclear effect on CAR-T expansion. 7 of 11 centers using ppx CS only use it for a subset of patients and 3 of 11 use it in all patients receiving axi-cel. The subset of patients selected for ppx CS was based on general institutional guidelines or treating physician preference. Criteria for those with institutional guidelines were variable but included high disease burden, older patients with comorbidities, and those requiring chemotherapy for bridging. A total of 22 pts at 4 centers received axi-cel between Jan 31, 2022, and June 15, 2022. A historical cohort of 22 pts was added to the no ppx CS group for those infused in 2021. Eleven (58%) pts received ppx CS and baseline characteristics at the time of apheresis are shown in Table 1. These were comparable between the 2 groups except for a shorter median time from apheresis to CAR-T infusion in the no ppx CS group. Among the entire cohort, 71% of patients required bridging therapy and only 20% (9/44) met ZUMA-1 eligibility criteria at the time of lymphodepletion. Any grade CRS occurred in 91% (40/44) pts, with grade ≥2 CRS in 43% (19/44). Any grade ICANS occurred in 61% (27/44) pts, with grade ≥2 ICANS in 43% (19/44) pts. The rates of grade ≥2 CRS, ICANS, the median time to CRS onset, ICANS onset, CRS duration, and ICANS duration were comparable between the 2 groups. Ten pts (23%) developed infectious complications within 30 days of CART. The day 30 ORR was 80% and was comparable between the 2 groups. In the ppx CS group (n = 22), 5 pts had progressed and 2 had died (both disease progression) at the time of data cut-off. Median event-free survival and overall survival had not been reached in either group (excluding historical cohort), due to short median follow-up of 15 weeks. Conclusions: Real-world adoption of ppx CS to mitigate toxicities of axi-cel varies considerably across sites in the US for multiple reasons. Since the FDA label change at least 50% of the centers surveyed had adopted the use of ppx CS. No significant differences in efficacy or CAR-T-associated toxicities were noted in the 2 groups, potentially due to selective use with patients at presumed higher risk of severe CRS and ICANS. A larger dataset and longer follow-up is needed for risk-stratified analysis and will be presented at the meeting. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Outcomes of Patients Treated with Low-Intensity Re-Induction Therapy for Persistent Disease after a Single Intensive Induction Cycle for Newly Diagnosed Acute Myeloid Leukemia (AML)

Introduction: Intensive chemotherapy with 7+3 or CPX-351 remains standard of care for fit adults with newly diagnosed AML. Nearly 50% achieve a remission after one induction cycle, and up to an extra 20% can achieve remission after a second intensive cycle. However, intensive re-induction increases morbidity through significant prolongation of cytopenias. Furthermore, certain patients (pts) may be less likely to respond to intensive re-induction, namely those with adverse risk disease. Recently, with effective non-intensive options, such as venetoclax (Ven) combinations, or IDH inhibitors, we offered low intensity re-induction to select pts with persistent disease after initial intensive therapy as a potential means of reducing morbidity, and potentially improving chance for response. This study describes the characteristics and clinical outcomes of pts with residual disease after intensive induction, treated with either Ven or IDH inhibitor re-induction. Methods: A chart review of ND-AML pts treated between 1/2017 and 2/2022 was performed. We identified pts who either received 7+3 or CPX-351 for initial induction. We then selected pts who had a nadir BM biopsy demonstrating persistent AML (>5% blasts), who then received either a Ven combination or an IDH inhibitor as next treatment. To characterize pt burden, we collected hospitalization duration, PRBC and platelet transfusion burden over 30 days after re-induction, neutropenic fever rates, ICU admission rates, and death within 30 days. We also collected clinical outcomes including CRc after 1 cycle of therapy, best response, proportion of pts proceeding to allogeneic HCT (alloHCT), and leukemia free survival (LFS). Results: A total of 15 pts were identified. Median age of pts was 61 years (22-67), 5 (33%) pts had ELN intermediate risk disease, 10 (67%) pts had ELN adverse risk disease; 5 (33%) pts had mutations in IDH1/2, and 4 (27%) pts had mutations in TP53. Most pts, 11 (73%), received initial induction with 7+3 chemotherapy; on post induction nadir marrow, a median 34% (10-90%) blasts were observed. For re-induction, 11 (73%) pts received a Ven combination (either with decitabine or azacitidine), and 4 (27%) received an IDH1 inhibitor (with azacitidine in 2 pts). Most common reason documented for re-induction choice was adverse risk disease, followed by presence of IDH mutation, followed by loss of fitness for additional intensive therapy. Median hospitalization duration from induction day 1 was 27 days (20-41); median time in hospital after re-induction was initiated was 6 days (0-27). After initiation of re-induction therapy, over the next 30 days, median number of PRBC transfusions administered to these pts was 1 (0-8), median number of platelet transfusions was 2 (0-17). Overall, 2 (13%) pts were re-hospitalized for neutropenic fever, including 1 (8%) pt who was admitted to the ICU and subsequently died (Table 1). In terms of response, 9 (60%) pts achieved a CRc after one cycle of low-intensity therapy. This includes 6 pts who received a Ven combination, and 3 patients who received ivosidenib (with or without azacitidine). Subsequently, 8 (73%) pts on a Ven combination achieved a CRc as best response, and 4 (100%) pts achieved CRc utilizing ivosidenib (Table 1). Ten (67%) pts proceeded to alloHCT. Overall, median leukemia free survival was 377 days (95% CI 235-518), and 7 (47%) pts remain alive at last follow-up (Figure 1). Conclusion: Among pts with residual disease after initial intensive induction, switching to a Ven combination or IDH inhibitor potentially reduces pt burden through shorter hospital stays, and lower burden of neutropenic fevers and transfusions. Furthermore, this strategy has promising efficacy, and serves as a successful bridge to alloHCT. A control cohort of pts receiving intensive re-induction is being composed from pts treated at our institution and will add further context. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Non-Canonical FLT3 Mutations (FLT3m) in Patients (Pts) with Newly Diagnosed Acute Myeloid Leukemia (AML) - Outcomes and Prognosis after FLT3 Inhibitor (FLT3i) and Venetoclax Based Regimens

Non-Canonical FLT3 Mutations (FLT3m) in Patients (Pts) with Newly Diagnosed Acute Myeloid Leukemia (AML) - Outcomes and Prognosis after FLT3 Inhibitor (FLT3i) and Venetoclax Based Regimens

Real-World Observational Study of Outcomes for Acute Myeloid Leukemia (AML) in Patients Treated with Glasdegib or Venetoclax in US Community Oncology Practices

Introduction: Glasdegib (GLAS) and venetoclax (VEN) were approved by the FDA in Nov 2018 for the treatment of AML in patients (pts) who are ≥75 years old or who have comorbidities that preclude intensive induction chemotherapy. Data related to the clinical outcomes of pts who receive these agents in the community oncology setting are limited. We conducted a retrospective, observational study to assess US real-word (RW) patient characteristics and clinical outcomes for pts who received a GLAS- or VEN-based regimen as first line (1L) therapy for AML. This study was observational and not designed or powered to compare characteristics or outcomes between pts treated with GLAS and those treated with VEN. We present RW findings comparing to the respective pivotal clinical trial populations (the BRIGHT AML 1003 trial which evaluated GLAS and the VIALE-A trial which evaluated VEN), including an exploratory analysis to match the characteristics of the RW cohorts to the clinical trials. Methods: A retrospective, observational, US multi-site, cohort chart review of adult pts who initiated 1L therapy for AML between 01 Dec 2018 and 31 Dec 2019 was conducted. Eligible pts had at least 6 months (mo) of follow-up since initiation of 1L (unless the pt died within this follow-up time, with known date of death), known cytogenetic risk profile, and had at least 1 bone marrow biopsy completed following index therapy initiation. Index therapy was either a GLAS- or VEN-based regimen (with low-dose cytarabine [LDAC], azacytidine [AZA), or decitabine). Pts treated in a clinical trial were excluded. The treating physician extracted all data for a given patient, including demographics, clinical characteristics, treatment patterns and dosing, transfusions, follow-up, disease response, and clinical outcomes. Results: 50 pts treated with GLAS as 1L therapy for AML, most of whom (82.0%) received GLAS in combination with LDAC, were followed for a median of nearly 7 mo, 28% of whom were still alive at data collection. The median age at initiation of 1L GLAS was 77 (47-89) years. Approximately half of 1L GLAS pts had an ECOG-PS of 0 or 1 at 1L therapy initiation. The median overall survival (mOS) for pts who received 1L GLAS was 6.9 mo (95% CI: 5.4-8.9); for comparison, the mOS for 88 GLAS- treated pts in the BRIGHT AML 1003 clinical trial was 8.8 mo. The median duration of follow-up was shorter in the RW cohort versus the trial (6.9 vs 27.1 mo). ECOG-PS 3 and poor cytogenetic risk score was noted in a greater proportion of RW 1L GLAS cohort vs BRIGHT AML 1003 trial (14% vs 0% and 58% vs 41%, respectively). The mOS for a subset of RW pts who matched all eligibility criteria for BRIGHT AML 1003 was 7.7 mo. 83 RW pts treated with VEN as 1L therapy for AML, the majority of whom (61.5%) received VEN in combination with AZA, were followed for a median of 8.4 mo and 38.6% of these pts were reported to be alive at data collection. The median age at initiation of VEN was 73 years and ECOG-PS of 0 or 1 was reported for 44.6% pts, 2 for 47.0% and 3 for 8.4%. The mOS of pts treated with 1L VEN was 8.4 mo (95% CI: 5.7-16.2); this compared to 286 VEN-treated pts in the VIALE-A trial with a mOS of 14.1 mo. The VEN RW cohort has shorter follow up compared to VIALE-A (8.4 mo vs 20.5). In comparison to pts treated with VEN in the VIALE-A trial, a greater proportion of pts in the RW VEN cohort had ECOG-PS scores of 2 or 3 (55.4% vs 45%) and poor cytogenetic risk (49.4% vs 36%). When the RW VEN cohort was matched to the eligibility criteria for VIALE-A, the RW mOS was not reached (n=23). Conclusions: In this RW observational study, the pt clinical and cytogenetic characteristics in the RW cohorts were less favorable for both GLAS and VEN than those observed in their respective clinical trials. In the RW, mOS was 1.9 mo lower for GLAS and 5.7 mo lower for VEN versus their respective clinical trials. This study was not comparative between GLAS and VEN, and indeed the pt populations were different with a higher median age and a higher proportion of ECOG-PS 3 in the GLAS RW cohort than the VEN RW cohort; the main combination agent also differed (LDAC or AZA). The settings and populations evaluated in these studies were unique and offer novel insights into the RW treatment patterns and effectiveness of both therapeutic options. Outcomes may be explained by differences in the characteristics of the RW cohorts and the eligibility criteria between the clinical trials.

Survival Outcomes for Patients in the QUAZAR AML-001 Trial Who Received Subsequent Therapy for Acute Myeloid Leukemia (AML) after Discontinuing Oral Azacitidine or Placebo

Introduction: While many older patients (pts) with AML attain complete remission (CR) after treatment (Tx) with intensive chemotherapy (IC), most will relapse and overall survival (OS) is poor, especially for pts who are not candidates for hematopoietic stem cell transplant (HSCT). In the randomized phase 3 QUAZAR AML-001 trial (NCT01757535), oral azacitidine (Oral-AZA), a hypomethylating agent (HMA), significantly prolonged OS (24.7 months [mo] vs 14.8 mo with placebo [PBO], P < 0.001) and relapse-free survival (10.2 vs 4.8 mo, respectively, P < 0.001) vs PBO in pts with AML in first remission after IC who were not candidates for HSCT (Wei AH, et al. N Engl J Med 2020;383:2526-2537). After discontinuing study drug, pts in QUAZAR AML-001 continued to be monitored for OS even if they received subsequent AML Tx. Given the high rate of relapse in older pts and the limited Tx options for relapsed/refractory AML, it is important to evaluate the impact of Oral-AZA maintenance Tx on the clinical outcomes for pts who received subsequent AML Tx after relapse. Methods: Eligible pts were aged ≥ 55 years, had AML with intermediate- or poor-risk cytogenetics at diagnosis, Eastern Cooperative Oncology Group performance status score ≤ 3, and had achieved a first CR or CR with incomplete blood count recovery (CRi) after IC ± consolidation Tx. Within 4 mo of achieving CR/CRi, pts were randomized 1:1 to receive Oral-AZA 300 mg or PBO once daily for 14 days per 28-day cycle. Randomized Tx could continue until pts developed relapse with > 15% blasts, unacceptable toxicity, or HSCT. These post hoc analyses assessed Kaplan-Meier (KM)-estimated OS and 1- and 2-year survival rates for pts who received subsequent AML Tx after relapse, both from the time of study randomization and from the time of receipt of first subsequent Tx, until death by any cause. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using Cox proportional hazards models stratified by age, cytogenetic risk, and receipt of consolidation Tx. These analyses were not prospectively powered to detect statistically significant differences between Tx arms. Results: At data cutoff (September 2020), 137/238 pts (58%) in the Oral-AZA arm and 172/234 pts (74%) in the PBO arm received subsequent AML Tx after discontinuing study drug. Demographic and disease characteristics at baseline in this subgroup were similar between the Oral-AZA and PBO arms and comparable to those for all pts in the trial (Wei AH, et al. N Engl J Med 2020;383:2526-2537). Pts from both Tx arms received similar classes of first-line subsequent Tx; 43% of pts in the Oral-AZA arm vs 45% in the PBO arm received IC, 50% vs 46% received lower-intensity therapies (including 25% vs 31% injectable HMAs), and in both arms 6% received supportive care and 1% received other Tx. In the Oral-AZA arm, 13 pts (9%) went on to receive HSCT, compared with 31 (18%) in the PBO arm. At a median follow-up of 51.7 mo, OS from the time of randomization for pts who received subsequent Tx was nominally prolonged with Oral-AZA vs PBO (median, 17.9 vs 12.5 mo, respectively; HR, 0.79 [95% CI, 0.62-1.0]) (Figure A). KM-estimated 1-year survival rates were 67% for Oral-AZA, compared with 51% for PBO, and 2-year rates were 41% and 29%, respectively. Median OS from the time of first subsequent Tx was similar in the Oral-AZA and PBO arms: 5.3 and 5.8 mo, respectively (HR, 1.1 [95% CI, 0.85-1.4]) (Figure B). Estimated 1-year survival rates from first subsequent Tx were 25% in the Oral-AZA arm and 31% in the PBO arm, and at 2 years, survival rates were 17% and 18%, respectively. Conclusions: Pts who received Oral-AZA during first remission, followed by subsequent Tx, showed a trend for improved OS from the time of study randomization compared with pts who initially received PBO. Survival outcomes from the start of first subsequent Tx were not meaningfully different between Oral-AZA and PBO. This suggests that Oral-AZA maintenance Tx can extend the duration of remission without influencing the clinical benefit of subsequent AML Tx. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Association of Clinical Characteristics at Diagnosis with Outcomes in Patients (Pts) with Lower-Risk Myelodysplastic Syndromes (LR-MDS) Treated with Erythropoiesis Stimulating Agents (ESAs): Findings from a Real-World Medical Chart Review in the US

Introduction: LR-MDS comprise a heterogeneous group of clonal myeloid neoplasms characterized by ineffective hematopoiesis, dysplasia(s), cytopenia(s), and relatively good-risk karyotypic and molecular abnormalities. The primary therapeutic strategy for pts with symptomatic LR-MDS is supportive care with red blood cell (RBC)/platelet transfusions and growth factor support such as treatment with ESAs. However, length of treatment and clinical outcomes vary among pts and are poorly understood in real-world clinical practice, particularly in the context of current guidelines. This medical chart review explores the impact of clinical characteristics at diagnosis on clinical outcomes of pts with LR-MDS treated primarily in community settings. Methods: This was a retrospective, observational, US multisite chart review of adult pts diagnosed with LR-MDS between January 1, 2015 and June 24, 2020. Eligible pts had ≥ 1 year of follow-up after diagnosis unless follow-up was < 1 year due to death. Pts who participated in a clinical trial were excluded. Demographic characteristics assessed included age at diagnosis, sex, and race/ethnicity. Four sets of subgroups were analyzed based on the following clinical characteristics collected at diagnosis: ring sideroblast (RS) status; erythropoietin (EPO) level; cytogenetic risk status; and transfusion burden (TB) level. TB level was defined as the number of RBC transfusion sessions for hemoglobin level < 9 g/dL and/or platelet sessions within the 56 consecutive days immediately prior to diagnosis, where transfusion independence (TI)/low TB was 0-3 RBC transfusion sessions and moderate/high TB was ≥ 4 RBC transfusion sessions. Treatment outcomes included physician-reported disease progression or ESA failure. ESA failure was determined per physician reports and/or calculated based on pre-specified criteria, which included discontinuation or switch of ESA-based therapy and/or increased TB within any consecutive 56-day period during ESA-based treatment. Statistical comparisons of characteristics and outcomes between subgroups were conducted using Fisher's exact or Chi-square tests for categorical data, Wilcoxon tests for continuous data, and log rank tests for Kaplan-Meier estimates. Statistical significance was defined as P ≤ 0.05. Results: Among 338 pts with LR-MDS identified, 23 (6.8%) were RS+, 14 (4.1%) had EPO levels ≥ 500 U/L, 65 (19.2%) had intermediate cytogenetics, and 37 (10.9%) had moderate/high TB at diagnosis. Median age at diagnosis was lower in pts with EPO levels ≥ 500 U/L vs < 500 U/L and in those with moderate/high TB vs TI/low TB. There were no statistically significant differences in race or sex among subgroups. The median follow-up time since diagnosis was longer for pts with RS+ status (50.9 months) vs those with negative/unknown RS status (27.0 months). No statistically significant differences in follow-up time were observed for the other subgroups (Table). A greater proportion of pts with moderate/high TB (94.6%) vs TI/low TB (74.1%) received any first-line (1L) systemic therapy for LR-MDS; no significant differences were observed for the other subgroups. Among those who received any 1L systemic therapy, a greater proportion of pts with disease progression at 1L was observed for those with EPO levels ≥ 500 U/L (50.0%) vs < 500 U/L (21.6%), intermediate (35.2%) vs good/very good (21.9%) cytogenetics, and moderate/high TB (45.7%) vs TI/low TB (22.4%) at diagnosis (Table). A smaller proportion of pts with EPO levels ≥ 500 U/L (14.3%) vs < 500 U/L (63.5%) at diagnosis received an ESA-based therapy at 1L. Among pts who received 1L ESA-based therapy, a greater proportion of pts with moderate/high TB (100%) vs TI/low TB (61.6%) experienced ESA failure. No statistically significant differences in 1L ESA failure were observed for the other subgroups (Table). Conclusions: This real-world medical chart review study in the US community care setting suggests that among pts with LR-MDS who receive 1L systemic therapy, more pts who have EPO levels ≥ 500 U/L, intermediate cytogenetics, and/or moderate/high TB at diagnosis may experience disease progression during treatment than those who do not. These results are in line with previous findings that EPO levels, cytogenetic status, and TB at diagnosis may be important predictors of 1L treatment outcomes. Additional studies with larger sample sizes may be useful to further explore these findings. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal