US Pts Research Articles

Treatment patterns and clinical outcomes in HER2-low metastatic breast cancer, 2018–2023: A retrospective observational study.

398 Background: Current treatment options for patients (pts) with hormone receptor–positive (HR+) human epidermal growth factor receptor 2–low (HER2-low) (immunohistochemistry [IHC] 1+, IHC 2+/in situ hybridization–negative) metastatic breast cancer (mBC) who progress after endocrine therapy (ET) with or without targeted therapy, including CDK4/6 inhibitors (CDK4/6i) or inhibitors of the PIK3CA/AKT/mTOR pathway, have been limited to chemotherapy (CT).In this study, we assessed recent treatment patterns and clinical outcomes in US pts with HR+/HER2-low mBC. Methods: This was a retrospective observational study using the nationwide Flatiron Health electronic health record-derived de-identified database. Pts aged ≥18 years with no prior cancer (excluding non-melanoma skin cancer), de-novo or recurrent HR+/HER2-low mBC diagnosed between January 2018 and December 2022, and who received any line of treatment (LOT) for mBC (excluding clinical trials) were included. Demographic and clinical characteristics were captured prior to and at the index date (date of mBC diagnosis). Pts were followed up from index date to death, last activity date, or end of the study (September 30, 2023). Real-world overall survival (rwOS) from mBC diagnosis and real-world progression-free survival (rwPFS) from the start of each LOT was calculated using the Kaplan-Meier method. Results: A total of 2692 pts were eligible. Median follow up from mBC diagnosis was 38.3 months (interquartile range [IQR] 24.4, 53.4) and median age at mBC diagnosis was 65.0 years (IQR 56.0, 73.0); 45.3% of pts had de-novo mBC. Median LOT was 2.0 (IQR 1.0, 3.0) up to the end of the study (55.1% of pts received second-line [2L], 28.9% third-line [3L], 15.2% fourth-line [4L], and 7.2% fifth-line [5L] therapy). Serial ET cycles accounted for 65.7% of 2L, 45.2% of 3L, 27.9% of 4L, and 18.5% of 5L therapy. The most common drug categories by LOT are shown in the Table. Median rwOS was 43.0 months (95% confidence interval [CI] 40.0, 46.0). rwPFS was 20.5 months (95% CI 19.0, 22.3) in first-line [1L] therapy, 15.6 months (95% CI 14.0, 18.9) in 2L, 17.1 months (95% CI 13.5, 22.8) in 3L, and 13.4 months (95% CI 9.9, not estimable) in 4L. Conclusions: Treatment of HR+/HER2-low mBC has been heterogenous by LOT and mainly characterized by initial use of ET-based therapy followed by higher CT use in later lines. This is associated with diminishing effectiveness, highlighting a need for new treatments. Top five drug categories by LOT, n (%). 1L (n=2692) 2L (n=1484) 3L (n=778) 4L (n=408) 5L (n=195) ET + CDK4/6i 1537 (57.1) 694 (46.8) 217 (27.9) 76 (18.6) 25 (12.8) Endocrine monotherapy 684 (25.4) 202 (13.6) 126 (16.2) 52 (12.8) 21 (10.8) ET + mTORi 9* 61 (4.1) 55 (7.1) 25 (6.1) 17 (8.7) ET + CT 50 (1.9) 74 (5.0) 45 (5.8) 29 (7.1) 22 (11.3) CT alone 269 (10.0) 270 (18.2) 210 (27.0) 161 (39.5) 82 (42.1) CDK4/6i alone 69 (2.6) 29* 8* 3* 3* *Not a top five drug category in the specified LOT.

Real-world outcomes of lisocabtagene maraleucel (liso-cel) in patients (pt) with Richter transformation (RT) from the Center for International Blood and Marrow Transplant Research (CIBMTR).

7010 Background: Pts with RT have poor prognosis and no standard treatment options with median OS of 3–12 mo (Eyre TA. Hematology Am Soc Hematol Educ Program 2023), indicating an unmet need. We report the largest cohort of real-world pts with RT treated with commercial liso-cel, an autologous, CD19-directed, 4-1BB CAR T cell product. Methods: This analysis included US pts with RT from the CIBMTR who received commercial liso-cel between 02/2021 and 02/2023. Primary outcomes included ORR, CR rate, duration of response (DOR), PFS, OS, and safety (including cytokine release syndrome [CRS] and immune effector cell-associated neurotoxicity syndrome [ICANS] based on Lee 2018 criteria, and prolonged cytopenia defined as grade [gr] 4 thrombocytopenia and/or neutropenia persistent at 30 d after infusion). Results: At data cutoff (08/04/2023), 30 pts with RT were included. Demographics and baseline characteristics at liso-cel infusion are shown in the Table; additional data regarding the pts’ indolent disease and treatment history will be provided in the presentation. Median time from leukapheresis to liso-cel infusion was 35 d (range, 28–63). At median follow-up of 12.3 mo, ORR was 76% among evaluable pts (n = 29) with 66% in CR. Median time to first response was 1.1 mo (range, 0–3.1). Median DOR was not reached (NR); 12-mo DOR rate was 77% (95% CI, 49.5–91). Median PFS (n = 29) and median OS (n = 30) were NR; estimated 12-mo PFS was 54% (95% CI, 33–72) and 12-mo OS was 67% (95% CI, 44–83). Overall, 70% of pts had CRS (gr 3, 0; gr 4, 3%; gr 5, 3% [this pt also had hemophagocytic lymphohistiocytosis]); most common CRS treatments were corticosteroids and tocilizumab (23%) and tocilizumab (20%). ICANS was seen in 47% of pts (gr 3, 17%; gr 4, 10%; gr 5, 0) and most commonly treated with corticosteroids (23%), antiepileptics and corticosteroids (7%), and antiepileptics (7%). Prolonged cytopenia occurred in 17% of pts. One pt had a second primary malignancy (gastrointestinal). Eight (27%) pts died, including 7 because of progression. Conclusions: Pts with RT have poor prognosis with a high unmet need. Here, we show that liso-cel provided meaningful clinical benefit with low incidences of gr ≥ 3 CRS and ICANS observed. The high CR rate is promising in this difficult-to-treat population, and longer follow-up in a larger cohort is needed. [Table: see text]

Real-world tumor BRCA testing patterns and PARP inhibitor use in HER2-negative metastatic breast cancer.

1113 Background: Testing for BRCA1/BRCA2 mutations (BRCAm) aids systemic treatment decisions for patients (pts) with metastatic breast cancer (mBC). This retrospective study explored real-world germline/tumor (g/t) BRCA testing patterns and PARP inhibitor (PARPi) use in US pts with mBC. Methods: Data from pts ≥18 years old diagnosed with HER2-negative mBC from 2014–2022 were captured in the nationwide Flatiron Health electronic health record-derived deidentified database. Patterns and timing of prospective or incidental BRCA testing were compared across mBC subtypes (hormone receptor-positive [HR+ mBC]/triple-negative mBC [mTNBC]) and disease stage (recurrent/ de novo). BRCAm prevalence was compared by testing modality and mBC subtype. PARPi initiation was assessed in pts with mBC diagnosed from 2018 onwards and a positive BRCAm test result. Clinical characteristics were compared by receipt of a BRCA test, testing modality, and PARPi initiation. Real-world overall survival (OS) by PARPi use was estimated using the Kaplan-Meier method. Results: Of 15,006 pts (including 12,349 with HR+ mBC; 1998 with mTNBC), 8178 (54.5%) did not receive any type of BRCA test, 4654 (31.0%) received a gBRCA test, 3075 (20.5%) received a tumor tissue DNA (ttDNA) test, and 1418 (9.4%) received a circulating tumor DNA (ctDNA) test. BRCA testing prevalence was numerically higher in pts with mTNBC (n=1164; 58.3%) than in pts with HR+ mBC (n=5323; 43.1%). As expected, testing prevalence was higher with ttDNA than with ctDNA (mTNBC: n=569 [28.5%] vs n=137 [6.9%]; HR+ mBC: n=2339 [18.9%] vs n=1224 [9.9%]). Over 93% of pts (recurrent and de novo) who received a tBRCA test were tested after an mBC diagnosis, and >1/3 were tested after first-line therapy, with median times from diagnosis to a ttDNA and ctDNA test of 127 and 431 days, respectively. Both gBRCA and tBRCA testing rates increased from 2014–2022, and testing occurred earlier in pts with recurrent than de novo disease. Among pts with tBRCAm, 66.0% had HR+ mBC, and 25.6% had mTNBC. BRCA1 mutations were more common in mTNBC (59.0%) than in HR+ mBC (22.9%) tumors. Of 219 pts with tBRCAm tumors who were diagnosed with mBC from 2018 onwards, PARPi was initiated in 39/74 (52.7%) pts with gBRCAm, 15/71 (21.1%) pts who were gBRCAm-negative, and 19/74 (25.7%) pts with gBRCAm status unknown. Among pts with g or tBRCAm and available OS data, median OS was numerically longer in pts who received PARPi (32.3 months [95% CI: 24.2, 47.4], n=128) versus pts who did not (29.0 months [95% CI: 21.9, 31.9], n=204; median follow-up time 23.2 months). Conclusions: While NCCN guidelines recommend gBRCA testing for all pts with mBC, more than half of pts with HER2-negative mBC (56.9% of pts with HR+ mBC) did not receive any BRCA test. Among pts with tBRCAm, ~2/3 had HR+ disease. Despite the potential benefits of PARPi for pts with BRCAm mBC, utilization remained low from 2018–2022.

Abstract PO3-12-05: Patient (pt)-provider communication challenges about side effects/toxicities from metastatic breast cancer (mBC) treatments

Abstract Introduction: Treatment decisions for ER+/HER2- mBC may be influenced by pt knowledge about treatment side effects, which is shaped by pt-provider communication. We conducted a survey of pts with ER+/HER2- mBC to better understand pt expectations and experiences of treatment toxicities, the extent they were discussed by the pts’ medical team (MT), and the sources/types of side effect information pts prefer. Methods: The 55-question, online ESR1 QUAlity of Life Survey 3 (EQUALS 3) survey was emailed to US pts from the Cure Media Group and authors’ contacts, and posted to private BC Facebook and Twitter pt groups for 2 weeks in June 2023. Eligible pts had ER+/HER2- mBC and reported changing treatments due to progression. Pts received a $10 gift card at survey completion. Survey answers were descriptively summarized. Results: 213 pts completed the survey; they were < 60 yrs of age (77%), White (44%) or Hispanic/Latino (48%), peri-/postmenopausal (54%), and urban-area residents (51%); and had college education (71%) and household income >$50K (66%). Most pts were on 2nd (36%) or 3rd+ (51%) therapy lines. Current mBC treatments were endocrine therapy ± targeted agent (70%), antibody-drug conjugate (8%), chemotherapy (11%), and others (10%). Most pts’ oncologists were female (65%), BC specialists (51%), and from an academic hospital (61%). Only half (49%) of surveyed pts felt extremely/very comfortable discussing side effects with their MT. Although 86% felt well informed about treatment toxicities, MTs did not proactively ask about pts’ greatest concerns on side effects for 15% of pts, nor about what side effects pts would find tolerable or intolerable for 25%. Oncologist/MT inquired about acceptability of side effects most often with treatment change (25%) or when brought up by the pt (20%), and at every single visit for only 19% of pts. Most pts felt extremely prepared for treatment toxicities (78%) and well prepared to manage them (86%), but 19% of pts still felt that their MT did not provide optimal guidance on managing potential side effects. Pt-centered conversations were most often missing: what rare but serious side effects to expect (44%), how to deal with potential side effects (39%), and what common side effects to expect (32%). Pts also reported that the likelihood of experiencing side effects (40%), what rare but serious side effects to expect (39%), and how to deal with potential side effects (28%) were not well presented. To facilitate treatment decisions, pts would like more time discussing treatment options (48%) or side effects (39%); additional written or visual resources on side effects (29%, 23%, respectively) or efficacy (39%, 8%); and the ability to ask questions and receive meaningful answers (39%), talk to other pts (20%), or listen to videos of their stories (11%). Pt testimonials (45%), toxicity descriptions/examples (42%), and toxicity management strategies (36%) were the most common additional forms of information that pts would like to have had on side effects. Conclusion: In this survey of pts with ER+/HER2- mBC, not all pts were comfortable discussing treatment toxicities with their MT, but MTs are mostly addressing side effects. However, there is still room for communication improvement and additional forms of toxicity information are needed for optimal decision-making. Despite generally feeling well prepared for toxicities, a significant proportion of pts report that the range and specifics of side effects and how to manage them were missing or not well presented in MT discussions. This survey highlights the need to improve both provider and pt education with the goal of effectively communicating toxicity specifics of mBC therapies, as well as the need for standardized pt education tools detailing risks and benefits of mBC therapies to assist pts in shared decision-making conversations. Citation Format: Sarah Sammons, Jane Meisel, Timothy Pluard, Kelly Shanahan, Fumiko Chino, Dario Trapani, Dominic Carroll, Monica Kozlowski, Elizabeth Attias, Nicole Kuderer. Patient (pt)-provider communication challenges about side effects/toxicities from metastatic breast cancer (mBC) treatments [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-12-05.

Perceptions of cancer prevention options for Lynch syndrome (LS) in a multi-national convenience sample.

77 Background: LS is among the most common cancer (CA) syndromes affecting 1:280 individuals and portends high lifetime CA risk. Clinical trials are currently evaluating whether frameshift peptide vaccination (FSPVAX) could reduce LS CA risk. FSPVAX enhances immune response to diverse FSP neoantigens in MSI-H tumors and has shown promising results in an MSH2-mutant mouse model and metastatic MSI-H CRC. However, negative public attitudes towards vaccination and evidence suggesting low uptake of ASA chemoprevention (CP) among patients with LS could undermine success of this novel therapy. Here, we benchmark attitudes towards FSPVAX for CA prevention against colonoscopy (COLO) and aspirin or NSAID chemoprevention (CP). Methods: The PREVENTLynchII survey (IRB 20-8014) was distributed electronically to 1) participants in the Fox Chase Cancer Center (FCCC) Risk Registry and 2) members of two online LS support groups. Patients were invited to complete the one-time survey after providing informed consent. Demographic and personal CA history were collected. Attitudes were measured on 9-point scales indicating low vs high agreement with belief statements: e.g. “Colonoscopy is a convenient way to lower my risk of LS-related CA.” Results: Overall 296 participants at FCCC, nationally, and internationally completed the survey. Median age was 52.6 years [23-78], 84% female, and 95% White. Affected genes included MLH1 (20.3%), MSH2/EPCAM (35.5%), MSH6 (28.7%), and PMS2 (15.5%). Use of CP was uncommon (32.1% and 5.1% respectively). Stratified analyses of COLO perceptions by sex, age, and personal history of CA showed no differences. Interestingly, US pts viewed ASA as more convenient than non-US, and with lower risk of side effects (p=0.007), but were no more likely to use or recommend CP. Compared to COLO, FSPVAX was overall viewed as more convenient, but side effect concerns were higher, and perceptions of efficacy were lower (all p<0.001), while compared to CP, FSPVAX was less convenient and fostered greater concerns about side effects, but was viewed as having higher potential preventive efficacy (all p<0.001). FSPVAX perceptions showed high variability: pts >50 (p=0.003) and CA pts (p=0.01) saw FSP as more convenient (p=0.003) than younger and unaffected pts. CA pts reported higher reassurance than unaffected (p=0.04), while those >50 were more likely to participate in an FSPVAX study (p=0.04). US pts perceived more side effect risk of FSPVAX than non-US (p=0.003). Conclusions: Concerns about ASA CP and FSPVAX convenience, side effects, and efficacy are common among US and international patients with LS. [Table: see text]

PRELIMINARY SAFETY, EFFICACY AND PHARMACOKINETICS (PK) RESULTS OF KN026 (A HER2 BISPECIFIC ANTIBODY) MONOTHERAPY IN ADVANCED SOLID TUMOR PATIENTS WITH HER2 EXPRESSION

Abstract Background KN026 is a novel bispecific antibody and simultaneously binds to two distinct HER2 epitopes which are the same domains as trastuzumab (ECD4) and pertuzumab (ECD2). It showed higher maximal binding than monospecific HER2 antibodies and favors that crosslinking of HER2 receptors could enhance the receptors internalization in preclinical studies. KN026 significantly inhibited the growth of human cancer cell lines and demonstrated obviously antitumor activity against different xenografts models. The encouraging efficacy and manageable safety of KN026 were reported in Chinese cancer patients (pts) with HER2 expression and ph3 study is ongoing in gastric cancer (NCT05427383). Methods The late line solid tumor pts with HER2 expression who were refractory to or ineligible for standard therapy were recruited in this phase I dose-escalation study in US (NCT03847168). All pts intravenously received KN026 monotherapy at ascending dose of 10 mg/kg (QW), 20 mg/kg (Q2W) or 30 mg/kg (Q3W). Dose escalation followed standard “3 + 3” design. Expansion was determined by Safety Monitoring Committee (SMC). The primary objectives were to evaluate safety and tolerability of KN026 and determine the MTD and/or RP2D. Safety was evaluated according to CTCAE v 5.0, and efficacy was assessed by RECIST 1.1. Results A total of 22 pts with median 4 lines prior treatment were enrolled, including 5 breast cancer pts, 3 gastric or gastroesophageal junction cancer pts and 14 other solid tumor pts. 21 pts were included in the efficacy analysis. The median age was 57.0 (47-79), with 8 males and 14 females and most of pts were Caucasian (72.7%). 3, 10 (7 at expansion phase), and 9 (6 at expansion phase) pts were treated at 10mg/kg, 20mg/kg, 30mg/kg, respectively. No dose-limiting toxicities (DLTs) were observed and MTD wasn’t reached. 20 pts (90.9%) occurred TRAEs and the common (≥20%) TRAEs were diarrhea (45.5%), fatigue (40.9%), chills (36.4%) and nausea (27.3%). Most of TRAE were Gr 1-2, and only 3 pts (13.6%) experienced ≥ Gr3 TRAE (anemia, fatigue and pneumonitis) without treatment discontinuation and death caused by KN026. 4 of 21 pts (1 at 10mg/kg, 2 at 20 mg/kg, 1 at 30mg/kg) achieved objective response (ORR 19.0%, 95% CI: 5.5, 41.9), and DCR was 61.9% (95% CI: 38.4, 81.9). The exposure of KN026 and T1/2 increased with dose escalation. Accumulation ratio of Cmax and AUC was 1.18-1.42 and 1.14-1.71. The concentration of Ctrough was over 20μM at all dose levels. There was only one positive ADA sample in 20 mg/kg group in C1D1. And the RP2D was 20mg/kg Q2W or 30mg/kg Q3W. Conclusion KN026 was well tolerated and showed the promising anti-tumor activity in US pts with HER2 expression. Besides, KN026 has well pharmacokinetic profile and favorable immunogenicity.

Platinum/taxane/pembrolizumab vs platinum/5FU/pembrolizumab in patients with recurrent/metastatic (r/m) head and neck squamous cell carcinoma (HNSCC).

6039 Background: Pembrolizumab +/- chemotherapy is standard of care for patients (pts) with r/m HNSCC. Despite approval of platinum/5FU/pembrolizumab based upon the KN-048 study, a taxane is often substituted for 5FU due to ease of administration and tolerability. No studies have directly compared these approaches. We describe nationwide patterns of taxane vs 5FU chemoimmunotherapy in r/m HNSCC and compare survival and time on treatment between the two. Methods: This study used the nationwide Flatiron Health electronic health record (EHR)-derived de-identified database, and included pts treated with frontline pembrolizumab plus platinum-based chemotherapy (either taxane or 5FU) for r/m HNSCC. Demographic, cancer, and clinical outcomes were summarized. Categorical variables were compared using Pearson’s chi-square test; continuous variables were compared using T-test. Overall survival (OS) was estimated using Kaplan Meier methodology, and compared using log-rank test. Multivariable Cox regression for overall survival adjusting for age, sex, race, year of diagnosis, ECOG performance status (PS), smoking history, primary tumor site, PD-L1, HPV status, cisplatin use, socioeconomic status, insurance, and practice type was performed, with multiple imputation by chained equations for missing variables. Results: Of 444 pts, 321 (72%) received 5FU and 123 (28%) received taxane (108 paclitaxel, 15 docetaxel). Use of cisplatin rather than carboplatin was higher in the 5FU group than the taxane group (16.8% vs 4.9%, p=0.001). Taxane use was higher in academic vs community practices (50.7% vs 23.9%, p<0.001); within community sites, Northeast states had highest taxane use (27.5%) and Western states had lowest taxane use (16.7%). Pts with Medicare or Medicaid were more likely to receive taxane (35.5%) vs commercial (23.6%) or other (26.7%) insurance. OS did not differ between taxane and 5FU groups (mOS 12.7 vs 13.5 months, p=0.743). On multivariable Cox regression, HR for death associated with taxane vs 5FU was 1.01 (95%CI 0.73-1.41). HPV positive status was associated with improved survival (HR 0.58, 95%CI 0.40-0.83). PS>1 (HR 1.38, 95%CI 0.96-1.98) and cisplatin use (HR 1.37, 95%CI 0.95-1.98) showed non-significant trends towards worse survival. Taxane-treated pts received more treatment cycles (mean 11.3 vs 8.8 cycles, p=0.015) and were on treatment slightly longer (mean 6.9 vs 6.0 months, p=0.289) than 5FU-treated pts. Conclusions: In US pts with r/m HNSCC undergoing chemoimmunotherapy, rates of taxane vs 5FU use vary by academic setting, geographic region, and insurance status. There was no difference in survival between 5FU and taxane, and taxane-treated pts received more cycles of therapy. Platinum-taxane appears to be a non-inferior alternative to platinum-5FU with pembrolizumab for r/m HNSCC, and should be allowed in clinical trials.

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]

Open-label study of darolutamide plus androgen-deprivation therapy (ADT) vs ADT in metastatic hormone-sensitive prostate cancer using an external control arm (ARASEC).

TPS5112 Background: Darolutamide (DARO) is a structurally distinct and highly potent androgen receptor inhibitor. In the phase 3 ARASENS study (NCT02799602) in patients (pts) with metastatic hormone-sensitive prostate cancer (mHSPC), DARO + ADT + docetaxel significantly reduced the risk of death by 32.5% vs ADT + docetaxel (hazard ratio 0.68; 95% confidence interval 0.57–0.80), with a favorable tolerability and safety profile. In the global (excluding US), phase 3 ARANOTE study (NCT04736199), DARO + ADT vs ADT alone is being evaluated in pts with mHSPC. ARASEC (NCT05059236) will complement ARANOTE by assessing DARO + ADT in US pts. As ADT alone is no longer an acceptable comparator in the US, the external control arm will be derived from the historical US CHAARTED study (NCT00309985). A real-world analysis of electronic health record data from pts with mHSPC (TIMES) indicated that there was minimal risk of historical time bias associated with the use of the external ADT alone arm from CHAARTED as a comparator for ARASEC (Shore N, et al . J Clin Oncol 2022;40(28 Suppl):Abstract 403). Methods: ARASEC is a phase 2, open-label, single-arm study enrolling pts with confirmed mHSPC and no prior systemic therapy. Pts will receive DARO 600 mg orally twice daily + ADT (luteinizing hormone-releasing hormone agonist/antagonist or orchiectomy). The external control arm will be derived from 394 pts with mHSPC treated with ADT alone in CHAARTED. To remove biases in evaluating outcomes that could arise due to differences in baseline profiles between arms, pts will be matched 1:1 using a propensity score (PS) summarizing baseline characteristics relevant to disease outcomes. Baseline variables will include age ( < 70 vs ≥70 years), Eastern Cooperative Oncology Group performance status (0–1 vs 2), CHAARTED-defined extent of disease (low vs high volume + bone metastases only vs high volume + visceral metastases ± bone metastases), and prior therapy (yes vs no; as a proxy for recurrent vs de novo disease). Matching patients with scores within a narrow window across the cohorts will ensure that pts in CHAARTED are representative of pts in the DARO + ADT arm. The primary endpoint is progression-free survival (PFS), as defined in CHAARTED. Secondary endpoints include overall survival, radiographic PFS, time to CRPC, undetectable prostate-specific antigen response rate ( < 0.2 ng/mL) at 6 months, and safety. Target enrollment for the DARO + ADT arm is 200 pts at 30 sites. The study will continue until either the event count threshold triggering the primary endpoint analysis has been met (161 PFS events) or all pts have been followed for ≥2 years, whichever occurs later. As of January 2023, 121 pts have been enrolled. A per-protocol, predefined matching exercise on the first 100 pts enrolled will be conducted to ensure that the planned sample size is adequate. Clinical trial information: NCT05059236 .

Real world (rw) racial differences in treatment (tx) patterns and clinical outcomes among patients (pts) with mCRPC.

95 Background: Contemporary rw data is needed to describe the heterogeneity of the tx landscape among diverse pt populations. This study assessed rw tx patterns and clinical outcomes among US pts receiving tx for mCRPC. Methods: Data from pts with mCRPC initiating first line (1L) tx between 2016 and 2019 were abstracted from medical charts. Clinical characteristics and tx patterns stratified by race (White [W], Black [B], and Other [O]) were compared using descriptive statistics. Rw progression-free survival (rwPFS) and overall survival (OS) were analyzed using Kaplan–Meier method. A multivariate Cox model explored associations between race and rwPFS/OS, controlling for confounders. Results: 122 physicians contributed data from 260 charts (W n=127, B n=81, O n=52 pts). The median age was 69 years; 64 (25%) had ECOG score ≥2. Common sites of metastases (mets) were bone (73%) and lymph nodes (34%); median Gleason score (GS) was 8.0, with no significant differences in sites of mets or GS among B and W pts. Most common txs prior to mCRPC included androgen deprivation therapy (ADT) monotherapy (39%), chemotherapy (CT; 15%), and novel hormonal therapy (NHT; 9%). Prior to mCRPC, more B pts were offered tx intensification with NHTs or CT compared with W pts (35% vs 14%). NHT was the most common 1L mCRPC therapy, followed by CT (Table). Compared with W pts, more B pts were offered NHT (65% vs 59%, P=0.44) and CT (26% vs 20%, P=0.38) in the 1L setting. Adjusted median rwPFS on 1L tx was 43.7 months (mo; 95% CI: 27–not estimable [NE]). A longer rwPFS was observed for B vs W pts; median rwPFS NE (95% CI: 34.7–NE) vs 34.7 mo (95% CI: 21.0–NE), hazard ratio (HR)=0.58 (95% CI: 0.35–0.97; P<0.05). B pts had numerically greater OS vs W pts, HR=0.58 (95% CI: 0.31–1.1; P=0.09). Conclusions: In this rw study of pts receiving 1L tx for mCRPC, rwPFS was better compared with clinical trial data, particularly among B pts, who were more likely to receive life-prolonging txs in the 1L setting. These data suggest B pts might respond better to systemic therapies compared with W pts, and disparities observed in other settings may be attributed to access barriers. [Table: see text]

Darolutamide plus androgen-deprivation therapy (ADT) versus ADT in metastatic hormone-sensitive prostate cancer: Open-label single-arm study with an external control arm (ARASEC).

TPS297 Background: Darolutamide (DARO) is a structurally distinct and highly potent androgen receptor inhibitor. In the phase 3 ARAMIS study (NCT02200614) in nonmetastatic castration-resistant prostate cancer (CRPC), DARO + ADT significantly improved metastasis-free survival and overall survival (OS) vs placebo + ADT, with a favorable tolerability and safety profile. In the phase 3 ARASENS study (NCT02799602) in metastatic hormone-sensitive prostate cancer (mHSPC), DARO + ADT + docetaxel significantly reduced the risk of death by 32.5% vs ADT + docetaxel (hazard ratio 0.68; 95% confidence interval 0.57–0.80; P<0.0001), with no additional adverse events. DARO + ADT vs ADT alone in patients (pts) with mHSPC is being evaluated in the ongoing, global (ex-US), phase 3 ARANOTE study (NCT04736199). The phase 2 ARASEC study (NCT05059236) will complement ARANOTE by evaluating DARO + ADT in US pts with mHSPC. Given that ADT alone is no longer an acceptable comparator in the US, an external control arm will be derived from a historical study. Methods: To participate in ARASEC, pts must have confirmed adenocarcinoma of the prostate, metastatic disease on conventional imaging for which they have not received prior systemic therapy, and Eastern Cooperative Oncology Group performance status (ECOG PS) 0–2. Pts will receive DARO 600 mg twice daily + ADT (luteinizing hormone-releasing hormone agonist/antagonist or orchiectomy). ADT can be started ≤4 months before DARO, and there must be no evidence of progression on ADT before DARO initiation. The external control arm will be derived from 394 pts with mHSPC treated with ADT alone in CHAARTED (NCT00309985). Pts in the active and control arms will be matched 1:1 on baseline characteristics such as age, ECOG PS, CHAARTED-defined extent of disease, prior therapy, and Gleason score. The propensity score (ie, the assessed probability that a pt is allocated to the DARO + ADT arm based on baseline profile) will be used to address bias in estimating differential effects, by matching pts with scores within a narrow window across the cohorts. The primary endpoint is progression-free survival (PFS), defined as the time from enrollment to prostate-specific antigen (PSA) progression, radiologic or symptomatic progression, clinical deterioration, or death, whichever occurs first, as defined in CHAARTED. Secondary endpoints are OS, radiographic PFS, time to CRPC, 6-month PSA response (<0.2 ng/mL), and safety. The study will continue until either the event count threshold triggering the primary endpoint analysis (161 PFS events) has been met or all pts have been followed for ≥2 years after enrollment, whichever occurs later. ARASEC is enrolling, with the first pt enrolled in November 2021. As of September 10, 2022, 59 pts have been enrolled. The target total enrollment is 200 pts at 30 sites. Clinical trial information: NCT05059236 .

Real-World Treatment (Tx) Patterns and Clinical Outcomes Among Patients (Pts) with Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL) Who Received at Least 2 Prior Lines of Therapy Including Bruton Tyrosine Kinase Inhibitor (BTKi) and/or B-Cell Lymphoma 2 Inhibitor (BCL2i)

Background: Real-world evidence highlighting the tx landscape and outcomes among pts with CLL/SLL who have received ≥3 lines (3L+) of systemic therapy that include a prior BTKi and/or BCL2i are limited. The objective of this study was to describe pt characteristics, tx patterns, and overall survival (OS) among these pts. Methods: This was a retrospective study using de-identified, electronic health records from the Flatiron Health database from 01/01/2011 to 02/28/2022. The study population included US pts aged ≥ 18 years with CLL/SLL who received ≥ 2 prior lines of therapy (LOT) including a BTKi (cohort 1) or both a BTKi and a BCL2i (cohort 2) and who initiated a subsequent LOT. For cohorts 1 and 2, respectively, the index date was defined as the start of 3L+ therapy after discontinuation of a BTKi and discontinuation of a BTKi and a BCL2i. Pts with any other primary cancers (except nonmelanoma skin cancer) within 12 months before the index date or during the follow-up period were excluded from the analytic cohorts. Descriptive analyses were conducted to examine pt characteristics and tx patterns. Time to discontinuation (TTD), time to next tx (TTNT), and OS for the index LOT were assessed using Kaplan-Meier (KM) method. TTD was defined as the time between index therapy start date and end date. TTNT was defined as the time between start of index therapy and start of subsequent LOT. Results: The study sample included 405 pts in cohort 1 and 57 pts in cohort 2, with a median follow-up of 18 and 11 months, respectively. The majority of pts (percent in cohort 1 and cohort 2) were aged ≥ 65 years (80.2% and 78.9%), male (60.2% and 50.9%), White (76% and 78.9%), and treated in the community setting (93.6% and 94.7%). Approximately 70% of pts in cohort 1 began their index LOT in 2018 or later, whereas 79% of pts in cohort 2 began their index LOT in 2019 or later. Pts in both cohorts were largely well functioning, with ECOG PS score ≤ 1 in 83.7% of cohort 1 and 68.0% of cohort 2. Disease transformation was reported among 8.9% of pts in cohort 1 and 14.0% of pts in cohort 2. Pts in cohort 1 received a median of 2 prior LOTs, whereas those in cohort 2 received a median of 3 prior LOTs. The most common txs observed in cohort 1 in the index LOT were BTKi monotherapy (20.0%), chemotherapy + anti-CD20 mAb (19.0%), BCL2i monotherapy (13.3%), and BCL2i + anti-CD20 mAb (13.1%). The most common txs observed in cohort 2 in the index LOT were BCL2i + anti-CD20 mAb (19.3%), phosphatidylinositol-3-kinase inhibitor monotherapy (17.5%), chemotherapy + anti-CD20 mAb (14.0%), and BCL2i monotherapy (12.3%). Median (95% CI) KM estimate of TTD for index therapy was 13.2 (11.1‒17.5) months and 7.1 (5.0‒11.8) months for cohorts 1 and 2, respectively. For pts who received a subsequent LOT after index therapy, the median (95% CI) KM estimate of TTNT was 11.3 (9.1‒12.6) months for cohort 1 and 6.6 (3.6‒10.1) months for cohort 2. The median (95% CI) OS was 33.1 (28.3‒40.0) months (Figure 1) and 16.6 (11.0‒27.5) months (Figure 2), and the 12-month OS estimate was 76.5% and 57.5%, for cohorts 1 and 2, respectively. Conclusions: The study findings highlight a significant unmet need in pts with 3L+ CLL/SLL. Real-world tx patterns observed in this study are reflective of a heterogenous tx landscape without the presence of a standard of care. The results indicate that pts receive similar txs as used in earlier LOTs. This rechallenging results in suboptimal disease control as indicated by short TTNT, TTD, and estimated OS. Study findings suggest that disease prognosis worsens among pts who were heavily pretreated (i.e., cohort 2, which received prior BTKi and BCL2i), despite the relatively small sample size. Although response and disease progression data were not captured in the Flatiron database, this study sufficiently demonstrates the need for newer and more effective options in the CLL/SLL tx landscape, which can delay disease progression while ensuring better disease control. Overall, these findings are generalizable to pts with CLL/SLL treated in the community setting in the US. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Minority Patients in the US Receiving Chimeric Antigen Receptor (CAR) T-Cell Therapy: A SEER-Based Simulation on Representation and Impact of Proximity to Authorized Treatment Center (ATC)

Background Patients (pts) of minority race or ethnicity are often underrepresented in oncology clinical trials (Awidi et al. JCO Oncol Pract. 2021) despite differences in the incidence of most cancer types, including B-cell malignancies, across races and ethnicities (Teras et al. CA Cancer J Clin 2016; Feng et al. Am J Epidemiol 2021). Both clinical trials and real-world (RW) studies have demonstrated significant clinical benefits of CAR T-cell therapy for pts with B-cell malignancies. To understand potential underrepresentation of minority pts, we conducted a series of simulations to estimate proportions of minority pts potentially eligible for either CAR T-cell trials or receiving standard-of-care CAR T-cell therapy in RW settings. We also assessed whether proximity to a CAR T-cell ATC is a barrier for treatment. Methods Race/ethnicity demographics (mutually exclusive groups of non-Hispanic White [NHW], non-Hispanic Black [NHB], non-Hispanic Other [NHO], and Hispanic [any race]) for US pts ≥ 20 years old with large B-cell lymphoma (LBCL), follicular lymphoma (FL), mantle cell lymphoma (MCL), and B-cell precursor acute lymphoblastic leukemia (B-ALL) were estimated for both trial and RW settings based on 5-year limited-duration prevalence prior to January 1, 2019 from the SEER Research Plus Data (17 registries, November 2021 submission), and US County Population Data (1969-2020). Estimated proportions and 95% confidence intervals (CIs) were simulated based on 3000 random samples per cancer type. Sample sizes for trial settings corresponded to US enrollment in clinical trials of axicabtagene ciloleucel (axi-cel) and brexucabtagene autoleucel (brexu-cel), while those for RW settings were based on accrual targets for post-authorization safety studies (PASS) using the CIBMTR registry (Table). Sampling was performed for counties within 50 miles [mi] of trial-associated ATCs or commercial ATCs for trial or RW settings, and for the entire US. Results As of January 1, 2019, approximately 177 million of 246 million people (72%) ≥ 20 years old lived within 50 mi of a commercial ATC in the US, of which 13% were NHB and 17% were Hispanic (Table). In clinical trial settings, the estimated proportion of NHB pts ≤ 50 mi of an ATC ranged from 5% in FL to 7% in LBCL (Table). The estimates were numerically higher, but not statistically significant, compared with actual enrollment in trials, except in B-ALL (7% [3%-12%] estimated vs 3% enrolled). Compared with actual trial enrollment, the estimated proportions (95% CI) of Hispanic pts were statistically higher across all indications (LBCL, 14% [10%-18%] estimated vs 7% enrolled; FL, 15% [9%-21%] estimated vs 5% enrolled; and B-ALL, 39% [30%-48%] estimated vs 29% enrolled) except in MCL (12% [4%-19%] estimated vs 15% enrolled). In RW settings, the estimated proportions of NHB pts were comparable to those in trial settings across all indications, whereas estimates of Hispanic pts were numerically lower (Table). The reported proportion of NHB pts with LBCL in PASS (5%) was statistically lower than the estimated proportion (8% [95% CI 7%-9%]). To further assess the impact of proximity to ATCs, the estimated proportions were compared between regions ≤ 50 mi of an ATC and the entire US. Proportions of NHB pts ≤ 50 mi of an ATC across all disease types were comparable with the estimates of the entire US, regardless of trial or RW settings (Table). While for Hispanic pts, the estimated proportions ≤ 50 mi of an ATC were numerically higher compared with the estimates of the entire US; but the estimates were comparable in RW settings. Conclusions This is the first simulation study to estimate the proportions of minority pts by considering disease prevalence and proximity to CAR T-cell ATCs. The possibility of patient underrepresentation is raised as the actual enrolled proportions of minority pts with certain B-cell malignancies were numerically lower than simulation-based estimates, even though most findings were not statistically significant. Based on the simulation, the estimated proportions of minority pts were comparable or even higher in regions close to ATCs indicating that proximity to ATCs may not be a key barrier for trial participation and accessibility of care. Further investigation into other factors influencing diversity in trials and accessibility of state-of-the-art cancer care in RW settings is warranted. MG and Z-HH contributed equally. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

329P Duration of adjuvant therapy in stage III colon cancer: A real world multi-institutional US-based experience

Since the publication of IDEA, the duration of adjuvant chemotherapy (CTX) in stage III colon cancer (CC) has shifted to a risk-stratified approach as 3 months (mo) of CAPOX vs 6 mo was found to be non-inferior in patients (pts) with low risk (LR) (T1-T3/N0-N1). High risk (HiR) (T4 or N2) disease failed to show non-inferiority, however 3-year DFS differences were less than 2% and only .1% when pts received CAPOX. However in the US cohort, pts did not receive CAPOX, possibly due to capecitabine intolerance. Herein, we performed a real-world evaluation of CTX in US pts with stage III CC. A retrospective review of stage III CC pts treated from 2016-2022 from 5 US academic medical institutions was performed. Pts were stratified into 3mo vs 6mo of CTX, HiR vs LR, and CAPOX vs FOLFOX. 3-year DFS and adverse events were recorded. A total of 443 pts were included. In the overall population, no difference in 3-year DFS was observed in 3 vs 6 mo of CTX (69.3 vs 71.0%, hazard ratio [HR] = 1.26, 95% CI (0.74, 2.17), adjusted p [aP] = 0.40), numerically less than was observed in IDEA. HiR pts were observed to have detriment in 3-year DFS with 3mo vs. 6mo CTX (34.0% vs 62.9%, HR = 1.51, 95% CI (0.77, 2.99), aP=0.23). Grade 3 adverse events (AE) of nausea, diarrhea, and hand/foot syndrome from capecitabine were higher than reported in IDEA.Table: 329PDFS by treatment, duration and riskCTXN (Events)36 Months DFS6 mo FOLFOX255 (76)71.8%6 mo CAPOX54 (17)67.5%3 mo FOLFOX37 (9)68.8%3 mo CAPOX97 (16)69.4%HiR vs LR6 mo LR126 (23)82.3%6 mo HiR183 (70)62.9%3 mo LR102 (13)81.2%3 mo HiR32 (12)34.0% Open table in a new tab In this real-world experience we observed no DFS benefit in pts treated with 3 vs 6mo CTX. In HiR pts treated with 3mo CTX, we observed a lower 3-year DFS rate compared to 6mo of CTX. The findings were not statistically significant due to low number of events in this cohort and was significantly lower than reported in IDEA. AEs were more prevalent in US pts compared to non-US pts in IDEA, likely due to capecitabine intolerance. Our study is the first to assess 3mo vs 6mo capecitabine based adjuvant CTX in a risk stratified US population and suggests discrepancies in DFS and AEs compared to IDEA in US pts who received CAPOX.

Real-world treatment patterns and survival of U.S. patients receiving second-line anti-programmed cell death protein-1 therapy for advanced/metastatic esophageal squamous cell carcinoma.

e16042 Background: Current second-line (2L) therapies for patients (pts) with advanced/metastatic esophageal squamous cell carcinoma (adv/met ESCC), including docetaxel, paclitaxel and irinotecan, have demonstrated modest survival gains. The National Comprehensive Cancer Network added the use of anti-programmed cell death protein-1 (PD-1) therapies (e.g., pembrolizumab, nivolumab) in the 2L to their guidelines in 2020. A real-world evidence study of 2L therapy for adv/met ESCC patients reported a median (95% CI) overall survival (OS) of 201 (153-249) days but did not include recently approved anti-PD-1 agents. Other studies of 2L anti-PD-1 therapy relied on claims data without the ability to report survival. Limited studies exist for 2L ESCC real-world treatment patterns. Herein, we characterize the real-world treatment patterns and OS for a recent cohort of US pts initiating an anti-PD-1 2L therapy. Methods: Pts (≥ 18 years of age) from the United States diagnosed with adv/met ESCC and initiating an anti-PD-1 2L therapy between January 1, 2011 and February 28, 2021 were selected using the electronic health record (EHR)-derived de-identified Flatiron Health database. Pt characteristics and descriptive treatment patterns were reported. Duration of therapy (DoT; start of therapy until last administration) was computed and OS (start of therapy until death or last recorded medical activity) was estimated by the Kaplan Meier method. Results: 60 pts were included who initiated an anti-PD-1 2L therapy. At 2L initiation, the median age was 66 years, 65% were male, 53% were white, 82% had a history of smoking, and 53% had stage IV disease. The median DoT was 92 days and median OS was 303 days with variability across agents (Table) . Of the 60 pts, a total of 21 (35%) initiated 3L therapy (8 initiated an anti-PD-1; 13 initiated a non-anti-PD-1). Of the 39 (65%) pts who did not initiate a 3L therapy, 16 (41%) died within 60 days of the final 2L administration, 12 (31%) lacked 60 days of follow-up observation, and the remaining 11 (28%) patients had no further 2L treatment. Conclusions: Compared to prior real-world analyses, use of anti-PD-1 therapy in the 2L for patients with advanced/metastatic ESCC may be associated with survival gains over other approved non-anti-PD-1 therapies. However, future real-world studies are needed to directly compare PD-1 inhibitors with other 2L therapies.[Table: see text]

86P Adjusting ORIENT-11 trial (O-11) results to a US patient population

O-11 demonstrated that adding sintilimab, a highly selective fully human IgG4 mAb that blocks the binding site of PD-1, to pemetrexed+platinum (SPP) improved progression free survival (PFS) in Chinese patients (pts) with advanced/metastatic nonsquamous NSCLC. To estimate the applicability of O-11 results to US pts, this post hoc retrospective study assesses the effect of SPP v placebo+pemetrexed+platinum (PPP) on PFS, after adjusting the O-11 population to reflect a target US population that would have been eligible for O-11.

The Impact of COVID-19 on Acute Myeloid Leukemia (AML) Treatment Patterns in the United States: Retrospective Analysis of an Electronic Medical Records (EMR) Database

INTRODUCTION: COVID-19 has disrupted healthcare access for patients (pts) with cancer, which may pose an especially high risk for pts with hematologic malignancies (NCI, 2021). The standard of care for newly diagnosed (ND) AML is induction with intensive chemotherapy (IC; “7+3”) ± consolidation for eligible pts; while during the COVID era, lower-intensity regimens, such as a hypomethylating agent (HMA) plus venetoclax (VEN), may be recommended over 7+3 to eligible pts to minimize transfusions and inpatient hospitalizations. For pts who achieved remission from induction, COVID-19 may have led some practitioners to reduce the number of consolidation cycles and/or lower the cytarabine dose used for consolidation. Transplantation, including hematopoietic stem cell transplantation (HSCT), has been severely impacted (even halted in some areas) during COVID-19 (NasrAllah, 2021). The influence of COVID-19 on AML treatment (Tx) and outcomes has yet to be adequately studied.OBJECTIVE: To assess the impact of COVID-19 on AML Tx patterns and survival in the real-world practice setting.METHODS: The Flatiron™ EMR database was used in this retrospective analysis of US pts aged ≥ 18 years with an AML diagnosis between 1 Jan 2018 and 31 Jan 2021 and who had ≥ 2 months of follow-up. Tx patterns and survival outcomes were compared between a Pre-COVID cohort, defined as pts diagnosed with AML between 1 Jan 2018 and 31 Dec 2019, and a Post-COVID cohort of pts diagnosed between 1 Mar 2020 and 31 Jan 2021. Pt characteristics and Tx patterns were assessed for all pts and in the Pre- and Post-COVID cohorts using summary statistics. Time to event analyses used Kaplan-Meier methods for survival curves and were compared by log-rank tests.RESULTS: In all, 2,133 pts met the selection criteria (mean age was 66.0 years, 57.5% were male, and 75.7% were treated in community practices); 1,582 (74.2%) pts were in the Pre-COVID cohort and 551 (25.8%) were in the Post-COVID cohort. Pt characteristics were generally similar between cohorts.In the Post-COVID cohort, use of IC and HMA-only induction decreased significantly, while induction with VEN + an HMA increased (Fig. A): 29.4% of pts (n=132) in the Post-COVID cohort received VEN + azacitidine and 19.8% (n=89) received VEN + decitabine, compared with 16.0% (n=190) and 9.0% (n=107), respectively, in the Pre-Covid cohort (P < 0.001, both comparisons). Time to induction was shorter in the Post-COVID cohort vs the Pre-COVID cohort (median 14 vs 18 days; P < 0.001).In all, 1,056 pts attained remission within 180 days of induction, including 774 Pre-COVID and 282 Post-COVID pts. Among them, 621 pts had a follow-up period of ≥ 180 days (394 pts Pre-COVID, 227 pts Post-COVID) and 41.1% (n=162) vs. 14.1% (n=32) of pts in the Pre- and Post-COVID cohorts, respectively, received consolidation (P < 0.001). Proportions of pts receiving maintenance therapy (MT) were 23.9% (n=94) and 17.6% (n=40) in the Pre- and Post-COVID cohorts, respectively (P = 0.069).Time to HSCT was significantly increased for pts in the Post-COVID cohort (P = 0.035; Fig. B), and rate of HSCT was reduced for Post-COVID pts vs Pre-COVID pts (19.0% vs 13.3%, respectively, at 180 days, and 31.3% vs 22.7% at 360 days). Estimated overall survival (OS) was significantly longer in the Pre-COVID cohort (P = 0.006 vs. Post-COVID); at 360 days of follow-up, estimated survival rates in the Pre- and Post-COVID cohorts were 68.3% vs. 51.3%, respectively.CONCLUSIONS: Induction with IC and HMAs was less frequent for pts diagnosed with AML during COVID-19, while induction with VEN + an HMA increased in these pts. Use of consolidation significantly decreased during COVID-19, and use of MT also decreased. These changes may have been influenced by inpatient resource constraints. Compared with the Pre-COVID cohort, Post-COVID pts were significantly less likely to receive HSCT, and longer HSCT waiting times suggest the pandemic affected access to timely transplantation, potentially due to hospital policies limiting surgeries, lack of available inpatient beds, or donor reluctance to visit a hospital during the pandemic. OS and 1-year survival were compromised in the Post-COVID cohort vs Pre-COVID pts, likely due to COVID-19 infection, but perhaps in part due to constraints on access to healthcare resources. These data suggest a need for oral Tx that can prolong remission while reducing clinic and inpatient visits, and that can bridge the gap until HSCT. [Display omitted] DisclosuresChen: Bristol Myers Squibb: Current Employment, Current equity holder in publicly-traded company. Rotter: SmartAnalyst Inc.: Current Employment. Potluri: Bristol Myers Squibb: Consultancy.

Interim analysis results of surufatinib in U.S. patients with neuroendocrine tumors (NETs).

4114 Background: Surufatinib (S) is a targeted inhibitor of tyrosine kinases VEGFR1, 2, and 3; FGFR1; and CSF-1R. A manageable safety profile and statistically significant efficacy of S have previously been demonstrated in patients (pts) with advanced NETs of extrapancreatic (epNET) and pancreatic (pNET) origin in 2 phase 3 randomized trials conducted in China (SANET-ep, NCT02588170; SANET-p, NCT02589821). Pts with epNETs achieved a median progression free survival (PFS) of 9.2 v 3.8 months (mo) (hazard ratio [HR] 0.334; p &lt; 0.0001), and pts with pNETs achieved a median PFS of 10.9 v 3.7 mo (HR 0.491; p = 0.0011), with S v placebo, respectively. S has recently been approved for the treatment (tx) of pts with epNETs in China. Methods: A phase 1, dose escalation (ESC)/expansion (EXP) trial was conducted to evaluate and confirm the efficacy and safety of S in US pts. ESC was completed, and the maximum tolerated dose and recommend phase 2 dose were determined to be 300 mg, same as previous trials. The EXP completed enrollment of the epNET and pNET cohorts, and the primary endpoint was investigator-assessed PFS rate at 11 mo. Secondary objectives included assessment of safety and PK. Results: 32 pts with heavily pretreated progressive NETs (16 epNET and pNET each) were enrolled in the dose EXP. The median age was 62.2 years (44-75) and 64.4 years (39-72) for epNET and pNET pts, respectively. 65.6% of pts received ≥3 prior lines of tx (median lines of therapy: epNET: 2 [2-5]; pNET: 4 [1-8]), and all pts previously received everolimus and/or sunitinib. As of the data cutoff of 30-Jun-20, 7 pts remained on tx (4 epNET; 3 pNET). The median number of tx cycles was 8.0 (2, 15) for epNET and 8.5 (2, 23) for pNET pts. The PFS rate at 11 mo was 51.1% (95% confidence interval [CI]: 12.8, 80.3) for pts with epNETs and 57.4% (95% CI: 28.7, 78.2) for pts with pNETs. The observed mPFS was 11.50 mo (95% CI: 6.47, 11.50) and 15.18 mo (95% CI: 5.19, NR) for pts with epNETs and pNETs, respectively. An objective response rate (ORR) of 6.3% was observed for pts with epNETs and 18.8% for pts with pNETs. A disease control rate of 90.6% (95% CI: 75.0, 98.0) was observed for all NET pts (93.8% epNET; 87.5% pNET). The safety profile of S remains consistent with previously completed trials. All pts (n = 32) had reported at least 1 adverse event (AE), and 24 pts (75%) reported AEs ≥grade 3. The most common AEs of any grade reported were fatigue (46.9%), hypertension (43.8%), proteinuria (37.5%), diarrhea (34.4%), vomiting (28.1%), and nausea (25.0%). The most commonly reported AEs ≥grade 3 ( &gt; 5%) were hypertension (37.5%); diarrhea (9.4%); and proteinuria, dysphagia, and anemia (6.3% each). AEs leading to tx discontinuation occurred in 21.9% of pts. Conclusions: S has demonstrated antitumor activity in heavily pretreated US pts with progressive NETs with a manageable safety profile that is consistent with 2 completed phase 3 studies. S continues to be studied in other ongoing clinical trials globally. Clinical trial information: NCT02549937.

Comparison of outcomes with ciltacabtagene autoleucel (cilta-cel) in CARTITUDE-1 versus real-world standard of care (RW SOC) for patients (pts) with triple-class exposed relapsed/refractory multiple myeloma (RRMM).

8045 Background: Pts with RRMM who are triple-class exposed (to immunomodulatory drugs [IMiDs], proteasome inhibitors [PIs] and an anti-CD38 antibody) cycle through multiple salvage regimens with progressively worse outcomes. CARTITUDE-1 (NCT03548207) is a single-arm phase 1b/2 study evaluating cilta-cel, a chimeric antigen receptor T-cell therapy with 2 B-cell maturation antigen–targeting single-domain antibodies, in pts with RRMM who received ≥3 prior lines of therapy (LOT) or were double refractory to an IMiD and PI, were triple-class exposed, had ECOG score of 0 or 1, and had disease progression ≤12 mo after the last LOT. Here, we compare efficacy outcomes for pts who received cilta-cel in CARTITUDE-1 (N = 97) with pts treated with SOC in a synthetic cohort from RW clinical practice. Methods: The Flatiron database, a primarily US community-based MM registry (Sep 2020 data cutoff), was used to identify a RW pt cohort who met CARTITUDE-1 (Sep 2020 data cutoff) eligibility criteria, including organ function. Progression-free/overall survival (PFS/OS) were compared between the cilta-cel–treated US pts and RW SOC cohort, using inverse probability of treatment (tx) weighting (IPTW) propensity scores adjusting for unbalanced baseline covariates of prognostic significance. Sensitivity analyses were conducted using multivariate Cox regression models and propensity score matching. Results: Baseline characteristics were similar between the 2 cohorts after propensity score weighting (Table). SOC tx regimens in the RW cohort primarily included pomalidomide (33%), carfilzomib (32%), daratumumab (13%), elotuzumab (16%), and ixazomib (8%). Pts had improved PFS and OS with cilta-cel (N = 97; median follow-up 12.4 mo) vs RW SOC (N = 196; median follow-up 9.2 mo) with a reduction in risk of progression/death and death by 84% and 78%, respectively (Table). Cilta-cel treatment benefit was robust across sensitivity analyses. Conclusions: Cilta-cel shows significantly better efficacy outcomes over RW SOC for PFS and OS, highlighting its potential as an effective tx option in pts with triple-class exposed RRMM. Clinical trial information: NCT03548207. [Table: see text]

A registry-based, observational safety study of inotuzumab ozogamicin (InO) treatment in patients (pts) with B-cell precursor acute lymphoblastic leukemia (ALL) who proceeded to hematopoietic stem cell transplant (HSCT).

7017 Background: InO is a CD22-directed antibody-drug conjugate indicated for treatment of relapsed/refractory (R/R) ALL. InO has been associated with hepatotoxicity and hepatic veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS), particularly post-HSCT. Registry data (Center for International Blood and Marrow Transplant Research [CIBMTR]) was analyzed to assess toxicity in pts with ALL who received InO prior to HSCT. Methods: CIBMTR patient data are being collected for a 5-year period after US approval of InO (Aug 2017 – Aug 2022). Data from US pts age ≥18 y treated with InO who proceeded to allogeneic HSCT were included. Using interim data at 3 y, we evaluated post-HSCT outcomes, including clinical status, overall survival, transplant-related (non-relapse) mortality (NRM), relapse, death after relapse (time from HSCT to death after the first 28 d from any cause with prior relapse/progression post-HSCT), and investigator-defined adverse events, including hepatic VOD/SOS. All statistical analyses are descriptive. Results: Data accrued from 18 Aug 2017 to 17 Aug 2020 for 131 adult pts (median age 40 y) who proceeded to first allogeneic HSCT: 31% in first complete remission (CR1), 46% in CR2, 13% in ≥CR3, 5% in 1st relapse, 2% in ≥3rd relapse, and 3% in primary induction failure. A majority (70%) had transplants from peripheral blood stem cells, and 47% involved an HLA-identical sibling or other related donor. Nearly half received myeloablative conditioning regimens. Before HSCT, 36% of pts received 1 cycle of InO, 46% had 2 cycles, and 17% had ≥3 cycles. Half (48%) received InO as a single agent. Median time from last dose of InO to HSCT was 2.0 mo (range: 0.4–26.2). At time of data-lock (11 Nov 2020), post-transplant data were available for 131 pts. Outcomes for these pts are shown in the Table. Among a subgroup of adults with active R/R ALL (n = 91) at time of HSCT (median of 4 lines prior therapy), VOD/SOS incidence within 100 d of HSCT was 18%. Conclusions: Incidence of VOD/SOS after first HSCT in InO-treated pts with R/R ALL in this study was similar to the 18–19% reported in pooled analyses of 2 clinical trials among InO-treated pts with R/R ALL (Marks et al, Biol Blood Marrow Transplant 2019) and in the INOVATE study (Kantarjian et al, Lancet Haematol 2017). The NRM at 1 y of 21% (23% R/R ALL) is lower than the NRM at 1 y of 38% reported in the pooled analyses of R/R ALL InO recipients.[Table: see text]