81 Background: In the phase 3 SUNLIGHT trial, FTD-TPI+bev improved overall survival (OS) as compared to FTD-TPI in treatment-refractory mCRC. Out of 492 pts in the study, only 7 (1.4%) pts self-identified as Black; therefore, the potential benefit of FTD-TPI+bev in this pt population was not well-examined. We present the largest analysis to date of real-world clinical outcomes of FTD-TPI and FTD-TPI+bev in Black pts with mCRC. Methods: We retrospectively identified Black adult pts with a documented exposure to FTD-TPI and diagnosis of mCRC at or prior to the initiation of FTD-TPI using United States-based electronic medical records and claims in the ConcertAI RWD360 dataset. Pts were categorized as having received FTD-TPI or FTD-TPI+bev. Kaplan-Meier analyses were used to compare the real-world overall survival (rwOS) and time to discontinuation (rwTTD) from the date of first exposure to FTD-TPI (index). Multivariate Cox regression analyses were used to control for pt characteristics including demographics, ECOG performance status (PS), comorbidities, metastatic sites, time from mCRC diagnosis to index, lab results, and prior receipt of regorafenib. Results: Out of 639 Black pts included in our study, 551 received FTD-TPI and 88 received FTD-TPI+bev. Index years were 2021-2023 for 26% and 92% pts receiving FTD-TPI and FTD-TPI+bev, respectively. Pts receiving FTD-TPI had median age 61 years; male 51.2%; any comorbidities 43.9%; ECOG PS 0-1 36.7%; median time from mCRC diagnosis to index 632 days. Pts receiving FTD-TPI+bev had median age 59 years; male 50.0%; any comorbidities 42.0%; ECOG PS 0-1 60.3 %; median time from mCRC diagnosis to index 579.5 days. The rwOS was significantly improved with FTD-TPI+bev as compared with FTD-TPI (10.8 vs 6.2 months, respectively; p=0.0001), similar to the SUNLIGHT study (Table). In the adjusted model, pts who received FTD-TPI+bev had a significantly lower risk of death as compared to pts who received FTD-TPI (hazard ratio [HR]=0.45; p<0.0001). The rwTTD was also significantly prolonged with FTD-TPI+bev as compared with FTD-TPI (3.8 vs 2.4 months, respectively; p<0.0001). In the adjusted model, pts who received FTD-TPI+bev had about half the risk of discontinuation as compared with pts who received FTD-TPI (HR=0.51; p<0.0001). Conclusions: This is the first study to compare the clinical outcomes with FTD-TPI vs. FTD-TPI+bev in Black pts with mCRC in the real-world setting. Our study confirmed OS improvement with FTD-TPI+bev as compared to FTD-TPI in Black pts with mCRC, as seen in the overall population of the SUNLIGHT trial. Current Study SUNLIGHT Black n rwOS months (95% CI) Black n OS months (95% CI) FTD-TPI 551 6.2 (5.7-6.9) 3 7.5 (6.3-8.6) FTD-TPI+bev 88 10.8 (7.8-16.0) 4 10.8 (9.4-11.8) HR 0.45 (95% CI 0.33-0.63; p<0.0001) HR 0.61 (95% CI 0.49-0.77; p<0.001)

79 Background: FTD-TPI+bev has shown survival benefit when compared to FTD-TPI alone in pts with mCRC and was approved in the U.S. in 2023. However, there is a lack of real-world data on outcomes for pts who received FTD-TPI+bev as compared to pts who received FTD-TPI. Methods: This retrospective study used data abstracted from electronic medical records and claims in the ConcertAI RWD360 dataset. Adult pts with a diagnosis of mCRC and exposure to FTD-TPI were included. Pts were categorized as having received FTD-TPI or FTD-TPI+bev based on first exposure to FTD-TPI (index date). Kaplan-Meier analyses were used to describe the overall survival (rwOS), real-world time to discontinuation (rwTTD), and time to next treatment or death (rwTTNTD) from the index date. Multivariate Cox regression analyses were used to control for patient characteristics, including demographics, ECOG performance status (PS), comorbidities, sites of metastatic disease, time from mCRC to index date, lab results, and receipt of prior regorafenib. Results: This study included 3,680 pts. The FTD-TPI cohort included 3,151 pts (median age 62 years; male 56.3%; White 63.3%; any comorbidities 40.6%; ECOG PS 0-1 34.8%; 2+ metastatic sites 25.4%; median time from mCRC diagnosis to index date 699 days). The FTD-TPI+bev cohort included 529 pts (median age 60 years; male 53.9%; White 68.1%; any comorbidities 34.4%; ECOG PS 0-1 51.4%; 2+ metastatic sites 25.1%; median time from mCRC diagnosis to index date 609 days). Prior to index date, 18.5% and 6.9% of pts had been exposed to regorafenib in the FTD-TPI and FTD-TPI+bev cohorts, respectively. FTD-TPI+bev significantly increased rwOS (median 9.4 [95% CI 8.0-10.1] vs 6.4 [95% CI 6.1-6.6] months; p<0.0001) and significantly decreased the risk of death (HR=0.68; p<0.0001) in the adjusted model. Other significant factors for rwOS included 2+ metastatic sites (vs.1 site, HR=1.16; p=0.002) and no receipt of regorafenib prior to index date of FTD-TPI (HR=0.80; p<0.0001). FTD-TPI+bev also significantly prolonged rwTTD as compared to FTD-TPI (median 3.5 [95% CI: 3.3-3.8] vs 2.4 [95% CI: 2.3-2.6] months; p<0.0001) and decreased risk of discontinuation (HR=0.65; p<0.0001) after adjusting for patient demographic and clinical characteristics. Additionally, the FTD-TPI+bev cohort had a significantly longer rwTTNTD as compared to the FTD-TPI cohort (median 5.0 [95% CI: 4.6-5.5] vs 3.9 [95%CI: 3.8-4.1] months; p<0.0001) in the adjusted model (HR=0.73; p<0.0001). Conclusions: This is the largest study to compare the clinical outcomes of pts receiving FTD-TPI and FTD-TPI+bev in the real-world setting. FTD-TPI+bev improved clinical outcomes including rwOS, rwTTD, and rwTTNTD, as compared to FTD-TPI in pts with mCRC. These findings align with the results of the SUNLIGHT trial.

34 Background: Trifluridine/tipiracil (FTD/TPI) is a standard of care therapy for patients with refractory metastatic colorectal cancer (mCRC). Recently, FTD/TPI in combination with bevacizumab (BEV) was also approved in this setting based on outcomes from the phase 3 SUNLIGHT trial, including statistically significant improvements in overall survival (OS) compared with FTD/TPI. This study examined demographic/clinical characteristics, treatment duration, OS, and healthcare resource use (HCRU), including outpatient/emergency room (ER) visits and hospitalizations, among patients with mCRC receiving FTD/TPI+BEV versus FTD/TPI in a real-world setting. Methods: This was a retrospective study of adults with CRC, who initiated FTD/TPI as monotherapy or in combination with BEV, identified from the Cerner Enviza electronic health records (EHR) database (12/2020–06/2023). A manual chart review of patients’ medical records was conducted where last follow-up was defined as death or last encounter in the EHR. Descriptive statistics were reported for all study variables; Kaplan Meier curves were used to estimate OS. Results: Of 197 patients abstracted, 122 (62%) received FTD/TPI+BEV combination therapy and 75 (38%) FTD/TPI monotherapy. Mean age was similar between the FTD/TPI+BEV and FTD/TPI groups (60.2 y vs 61.8 y) and 66% vs 63%, respectively, were male. Mean Charlson Comorbidity Index was 8.9 for the FTD/TPI+BEV group vs 8.5 for the FTD/TPI group and body mass index was 26.9 kg/m 2 vs 27.3 kg/m 2 , respectively. Most patients received treatment in the third or fourth line (65% FTD/TPI+BEV; 75% FTD/TPI). Median follow-up was 5.3 and 4.6 mo, respectively. Mean duration of treatment was 3.7 vs 2.7 mo for FTD/TPI+BEV vs FTD/TPI monotherapy (Table). Median OS (from FTD/TPI initiation to death) was 11.5 and 9.6 mo for FTD/TPI+BEV and FTD/TPI groups (number of deaths: 38 and 22), respectively. Patients receiving FTD/TPI+BEV had numerically more outpatient visits (20.5 vs 13.9), but similar ER visits (0.5 each) and slightly fewer hospitalizations (1.1 vs 1.2) compared with FTD/TPI, during follow-up. Overall HCRU costs were similar between groups (27,175 vs 27,891). Conclusions: This real-world study supports the value of FTD/TPI+BEV combination therapy vs FTD/TPI monotherapy as seen in the SUNLIGHT trial. Patients with FTDTPI+BEV were treated for longer duration with improved OS and no difference in trends for HCRU and associated costs. [Table: see text]

Introduction: Decitabine and cedazuridine (DEC-C), an oral hypomethylating agent (HMA), was approved for the treatment of adult patients with myelodysplastic syndromes (MDS) in July 2020 in the USA. DEC-C is the only oral HMA approved for MDS; the other two HMAs approved for MDS, decitabine and azacitidine, are administered intravenously (IV) or subcutaneously (SC). This study aimed to examine real-world treatment outcomes among MDS patients treated with oral DEC-C compared to IV/SC HMAs using the ConcertAI real-world electronic health records database. Methods: Patients aged 18 years and older diagnosed with MDS (based on ICD-10 code: D46*) and treated with HMAs as first treatment on or after July 1, 2020 post initial MDS diagnosis in ConcertAI's RWD360™ dataset linked to open claims were included in the study. The primary outcome was real-world overall survival (rwOS), and secondary outcomes included acute myeloid leukemia (AML)-free survival (defined as time from index HMA to AML transformation or death), and time to next treatment (rwTTNT). Kaplan-Meier survival analysis methods and Cox regression analysis were utilized to evaluate rwOS, AML-free survival, and rwTTNT among patients treated with oral DEC-C compared to IV/SC HMAs. Patient demographic (age, race, gender, region) and clinical characteristics (comorbidity index score, ECOG, body mass index, high-risk MDS based on diagnosis code, prior HMA use, and pre-MDS conditions which included anemia, thrombocytopenia, leukopenia, and neutropenia) were adjusted in the Cox models. Results: A total of 2,101 patients with MDS were treated with HMAs as first treatment post MDS diagnosis, with 405 treated with oral DEC-C and 1,696 treated with IV/SC HMA. Of those treated with IV/SC HMA, 1,250 received azacitidine and 446 received decitabine. The overall cohort had a median age of 75 years at the start of index HMA, 73.3% White, 64.4% male, 63.4% pre-MDS conditions, 5.3% prior HMA use, 44.5% ECOG 0-1 at index HMA, 20.4% high-risk MDS, and 11.6 months median follow-up from index HMA treatment. Baseline demographic and clinical characteristics were comparable between the oral DEC-C and the IV/SC HMA cohorts. The median rwOS for the overall sample was 19.3 months, and patients who received oral DEC-C had numerically longer median rwOS compared to those treated with IV/SC HMAs (23.2 vs. 19.0 months), but this difference was not statistically significant (p=0.235). After adjusting for demographic and clinical characteristics, mortality risk for patients treated with DEC-C was slightly lower though not statistically significantly different compared to IV/SC HMAs (hazard ratio [HR]=0.94; 95% confidence interval [CI]: 0.80-1.11, p=0.442).The median AML-free survival was 13.7 months overall, and the DEC-C cohort had a significantly longer AML-free survival compared to the IV/SC HMA cohort (16.5 vs. 13.3 months, p=0.009). Patients treated with oral DEC-C had a 16% lower risk of AML transformation or death (HR=0.84; 95% CI: 0.73-0.98; p=0.027) compared to those treated with IV/SC HMAs in the adjusted model. The median rwTTNT was 7.8 months for overall, 9.4 months for the oral DEC-C, and 7.4 months for the IV/SC HMA cohort, respectively (p<0.001). Patients treated with oral DEC-C were 18% less likely to receive a next treatment (HR=0.82; 95% CI: 0.71-0.94; p=0.004) compared to those treated with IV/SC HMAs in the adjusted model. Conclusions: This real-world study is among the first and largest to date that examines clinical outcomes among MDS patients who initiated treatment with oral DEC-C compared to IV/SC HMAs. While study results indicate comparable rwOS among patients treated with oral DEC-C as those treated with IV/SC HMAs, patients treated with oral DEC-C appeared to have a significantly longer AML-free survival and rwTTNT. These findings support consideration of oral DEC-C as an alternative to parenteral HMA therapy.

Background: Hypomethylating agents (HMAs) are guideline-recommended treatment for higher-risk myelodysplastic syndromes/neoplasms (MDS). However, a prior survey of patients with MDS reported challenges with intravenous (IV) and subcutaneous (SC) HMA therapies, including pain related to treatment administration and interference with daily activities; most patients also indicated a preference to switch to an oral therapy if one were available. Objectives: This study evaluated the perspectives of US patients with MDS receiving oral decitabine/cedazuridine (DEC-C), an alternative to IV/SC HMAs. Methods: An online survey was conducted among adult patients with MDS in the United States (10 November 2022 to 5 December 2022) who had filled a prescription for oral DEC-C between 2021 and 2022. Results: A total of 150 patients completed the survey; 61% were aged ⩾60 years and 63% were male. Of these, 123 (82%) were still receiving oral DEC-C, and 27 (18%) had stopped oral DEC-C treatment. Half (50%) of patients had received oral DEC-C for ⩾6 months. The majority reported that treatment was convenient (83%) and that they were satisfied with treatment (86%). Most patients also reported very little/no interference with regular daily activities (82%), social activities (78%), and productivity (78%). When queried about negative impacts on quality of life (QOL), treatment side effects were the most commonly reported (30% of respondents). Among patients who had previously received IV/SC HMAs ( n = 91), most agreed that oral DEC-C interfered less with daily life (91%) and had experienced improvement in QOL (85%) compared with previous treatment; 91% reported that oral DEC-C reduced the number of times they needed to travel to a healthcare facility. Conclusion: Survey results suggest very little/no impact on regular daily activities and improved QOL with oral DEC-C relative to IV/SC HMAs, highlighting the potential for oral DEC-C to reduce the treatment burden associated with parenteral HMA therapy.

6568 Background: Patients spend substantial time receiving cancer care. Patients with higher-risk MDS treated with hypomethylating agents (HMAs) are generally older and have a median life expectancy of 11–17 months. Patients receiving parenteral treatment for MDS spend significant time in clinics receiving HMA treatment; as such, information on the time burden of treatments (“time toxicity”) is needed to help clinicians guide patients and caregivers with alternative routes of administration. The development of oral HMA therapies offers a strategy that mitigates the time toxicity associated with MDS treatment by increasing the number of “home days” for patients. This study details the time burden among patients with MDS receiving oral HMA therapy versus those receiving intravenous and subcutaneous (IV/SC) HMAs. Methods: This was a retrospective analysis of adult patients with MDS initiating HMA therapy (oral or IV/SC HMA), using the US Cerner Enviza claims database (08/2020–08/2022). Propensity score matching (1:1) was performed on the treatment groups to balance confounding factors; matched cohorts were analyzed (N=158 each). The total direct healthcare encounter days for oral and IV/SC HMA administered patients were evaluated based on the number of healthcare encounter days spent on parenteral HMA administration (0 days for oral HMAs), outpatient, inpatient, and emergency room (ER) visits, and infusion days. Only distinct encounter days were included in the total count; multiple visits in a day were de-duplicated. Mean (SD) healthcare days for oral versus IV/SC HMA groups were calculated for each type of healthcare encounter and summarized. Results: Patients receiving oral HMA incurred a mean total of 15.2 healthcare encounter days compared with 32.8 days for those receiving IV/SC HMAs (Table). Most encounter days for the oral HMA cohort were in the outpatient setting (34.9%) while most encounters for the IV/SC HMA cohort were attributed to receiving parenteral HMA administration (55.5%), followed by inpatient (16.2%) and outpatient visits (14.9%). Conclusions: This study, which is the first report to date of time toxicity in MDS among patients treated with HMA therapy, revealed that patients receiving oral HMA incurred half the time burden of those receiving IV/SC HMAs. Further research is warranted to validate these results in a larger patient cohort and compare these findings with other cancer therapies. [Table: see text]

Introduction: Hypomethylating agents (HMAs) are recommended standard of care for patients with higher-risk myelodysplastic syndromes (HR-MDS). HMA therapies include intravenous (IV) or subcutaneous (SC) decitabine and azacitidine; however, parenteral administration of HMAs has been associated with increased patient burden. The oral HMA decitabine and cedazuridine (DEC-C) was FDA-approved in July 2020 for the treatment of MDS, and offers an alternative to IV/SC HMAs, with similar pharmacokinetic exposure and response rates compared to IV decitabine. This study examined treatment patterns among patients with MDS receiving oral DEC-C compared with IV/SC HMAs in real-world clinical practice. Methods: This was a retrospective analysis using the US Cerner Enviza claims database; medical and prescription claims data for patients were linked to mortality data from Datavant. Adults aged ≥18 years, who were diagnosed with MDS (ICD-10-CM code D46.x; all risk levels), and who had initiated a HMA (≥1 claim; August 1, 2020─August 31, 2022) were included; index date was defined as the first pharmacy or medical claim for DEC-C or IV/SC HMAs, respectively. Patients had variable follow-up after index and were followed until end of enrollment, death, or end of study. Propensity score matching (PSM; 1:1) was performed to balance for confounding factors (age, sex, acute myeloid leukemia [AML] diagnosis, Charlson Comorbidity Index [CCI] score, and red blood cell [RBC] transfusion); adjusted bivariate analysis was used to compare outcomes between treatment groups. Longitudinal persistence was assessed according to the number of cycles of therapy received during follow-up, where a cycle was defined as either 3-10 days of administration of index IV/SC HMA or 1 claim for oral DEC-C, within a 28-day cycle. Results: Of 1569 patients included, 160 (10.2%) received DEC-C and 1409 (89.8%) received IV/SC HMAs. In the DEC-C cohort, median age was 72.5 years and 66.9% were male; in the IV/SC cohort, median age was 69.0 years and 58.2% were male. Two-thirds of patients newly initiated HMAs during the study period (69.4% for DEC-C and 72.2% for IV/SC HMAs); 30.6% of the DEC-C cohort had switched from prior IV/SC HMA treatment. Both groups had high levels of comorbidity; 55.6% of patients in the DEC-C cohort and 58.4% in the IV/SC HMA cohort had CCI scores of ≥3, and 14.4% and 23.8%, respectively, had an AML diagnosis. During the 6-month pre-index period, half (55.3%) of patients in both groups received RBC transfusions, and one quarter (25.9%) received platelet transfusions. After matching, there were 158 patients in each treatment cohort and all covariates included in the PSM were balanced (standardized mean difference <0.2). Median age was 72.0 years and 74.0 years for the DEC-C and IV/SC HMAs matched cohorts, respectively, and 66.5% and 69.6%, respectively, were male. Mean CCI scores were 3.45 for DEC-C and 3.15 for IV/SC HMA groups and 14.6% and 15.8%, respectively, had an AML diagnosis pre index. Longitudinal persistence was comparable between the matched DEC-C and IV/SC cohorts during the first 6 months post-index, with similar proportions receiving the maximum number of treatment cycles (based on a 28-day cycle) at each month following index (73.8% vs 71.1%, 46.5% vs 48.7%, 28.6% vs 24.8%, for 2, 4, 6 months, respectively; Figure). However, a trend towards improved persistence with DEC-C versus IV/SC HMAs was observed in patients receiving treatment beyond 6 months (25.0% vs 17.0%, 18.5% vs 9.0%, 11.4% vs 7.6%, for 8, 10, 12 months, respectively). Mean time to discontinuation of treatment was also numerically higher for DEC-C compared with the IV/SC HMA group (87.7 vs 82.0 days); however, differences were not statistically significant. Conclusions: This study, which is to our knowledge the largest real-world report of oral DEC-C use to date, reveals similar but high levels of disease burden and comorbidities among patients with MDS receiving oral DEC-C and parenteral HMA therapy. Trends in treatment patterns suggest comparable persistence with oral DEC-C and IV/SC HMAs at early stages of therapy and improved persistence with oral DEC-C beyond 6 months. These data support the consideration of oral DEC-C as an alternative to chronic parenteral HMA therapy, with the potential for oral DEC-C to reduce the treatment burden associated with administration of IV/SC HMAs.

BACKGROUND:Alterations in fibroblast growth factor receptor 2 (FGFR2) have emerged as promising drug targets for intrahepatic cholangiocarcinoma, a rare cancer with a poor prognosis. Futibatinib, a next-generation, covalently binding FGFR1-4 inhibitor, has been shown to have both antitumor activity in patients with FGFR-altered tumors and strong preclinical activity against acquired resistance mutations associated with ATP-competitive FGFR inhibitors.METHODS:In this multinational, open-label, single-group, phase 2 study, we enrolled patients with unresectable or metastatic FGFR2 fusion-positive or FGFR2 rearrangement-positive intrahepatic cholangiocarcinoma and disease progression after one or more previous lines of systemic therapy (excluding FGFR inhibitors). The patients received oral futibatinib at a dose of 20 mg once daily in a continuous regimen. The primary end point was objective response (partial or complete response), as assessed by independent central review. Secondary end points included the response duration, progression-free and overall survival, safety, and patient-reported outcomes.RESULTS:Between April 16, 2018, and November 29, 2019, a total of 103 patients were enrolled and received futibatinib. A total of 43 of 103 patients (42%; 95% confidence interval, 32 to 52) had a response, and the median duration of response was 9.7 months. Responses were consistent across patient subgroups, including patients with heavily pretreated disease, older adults, and patients who had co-occurring TP53 mutations. At a median follow-up of 17.1 months, the median progression-free survival was 9.0 months and overall survival was 21.7 months. Common treatment-related grade 3 adverse events were hyperphosphatemia (in 30% of the patients), an increased aspartate aminotransferase level (in 7%), stomatitis (in 6%), and fatigue (in 6%). Treatment-related adverse events led to permanent discontinuation of futibatinib in 2% of the patients. No treatment-related deaths occurred. Quality of life was maintained throughout treatment.CONCLUSIONS:In previously treated patients with FGFR2 fusion or rearrangement-positive intrahepatic cholangiocarcinoma, the use of futibatinib, a covalent FGFR inhibitor, led to measurable clinical benefit. (Funded by Taiho Oncology and Taiho Pharmaceutical; FOENIX-CCA2 ClinicalTrials.gov number, NCT02052778.).

49 Background: Trifluridine/tipiracil (FTD/TPI) and regorafenib are among the limited treatment options in later lines of therapy for patients with advanced colorectal cancer (CRC). While these treatments have demonstrated similar efficacy, differences have been observed in tolerability and data on the impact of such differences on real-world outcomes are limited. To better understand the real world use of FTD/TPI and regorafenib in the US, we report data for adherence/persistence among patients with CRC initiating these therapies. Methods: This was a retrospective cohort study among adults with CRC identified from the IBM MarketScan Commercial Claims and Medicare Supplemental Databases, who initiated FTD/TPI or regorafenib (index) from October 2015-September 2019 and had 6 months of continuous enrollment before the index date. Follow-up was until disenrollment or end of study period. Treatment cohorts were propensity score 1:1 matched, adjusting for differences in socio-demographics, comorbidities, and other baseline characteristics. Adherence and persistence outcomes included time to discontinuation (medication gap of >45 days), medication possession ratio (MPR; number of treated days/ duration of treatment), proportion of days covered (PDC; number of treated days/ days in specified time period), and number of prescriptions received. Results: A total of 1477 patients were included: 892 initiating FTD/TPI (60%) and 585 regorafenib (40%). Demographics were similar prior to matching: mean age was 58 and 59 years, and 57% and 59% were male, in the FTD/TPI and regorafenib groups, respectively. Mean Charlson Comorbidity Index score (excluding cancer) was 0.69 for FTD/TPI initiators and 0.62 for regorafenib initiators. For the matched cohorts (n=585 in each), measures of adherence and persistence (Table) showed longer time to discontinuation (2.5 vs. 2.0 months; p<0.01), and a higher MPR (0.90 vs. 0.87; p<0.01), PDC (at 3 months, 0.74 vs. 0.63; p<0.01), and proportion of patients receiving ≥2 prescriptions (76% vs. 63%; p<0.01) with FTD/TPI vs. regorafenib. Conclusions: Results of this real-world study suggest that patients with CRC initiating FTD/TPI have improved adherence and persistence with therapy compared with those initiating regorafenib. Reasons for this difference and potential impacts on health outcomes require further study. [Table: see text]

440 Background: Futibatinib, an irreversible FGFR1–4 inhibitor, is being investigated for the treatment of advanced intrahepatic cholangiocarcinoma (iCC) with FGFR2 fusions/rearrangements. We conducted an indirect treatment comparison to evaluate efficacy outcomes with futibatinib for advanced iCC patients from the FOENIX-CCA2 trial (NCT02052778) relative to published data for chemotherapy and FGFR inhibitors. Methods: A systematic literature review was conducted to identify clinical trials for FGFR inhibitors published 01/2015-02/2021, with additional targeted searches for chemotherapy data. A simulated treatment comparison was conducted using individual-level patient data from FOENIX-CCA2 and published aggregate data from comparator trials, applying regression models to adjust for between-trial differences in baseline characteristics. Population-adjusted Cox regression models were used for base case time-to-event outcomes (progression-free survival [PFS], overall survival [OS], duration of response [DOR]) and binomial-logistic regressions for binary outcomes (objective response rate [ORR]). Results: Two studies of FGFR inhibitors among previously treated patients with FGFR2 fusions/rearrangements were identified with sufficient data for analysis: FOENIX-CCA2 (n=103) and FIGHT-202 (n=107, pemigatinib). Two studies were identified for chemotherapy in this setting (an analysis of prior systemic therapy in the FIGHT-202 cohort [n=53] and a natural history study using a clinicogenomic database [n=71]). Comparisons of futibatinib with chemotherapy showed significantly lower risk of progression or death with futibatinib (table). Comparisons of futibatinib with pemigatinib showed similar outcomes between treatments (table), however, there was a numerical advantage for futibatinib in all efficacy parameters. Conclusions: Data suggest that futibatinib provides longer survival vs chemotherapy among previously treated advanced iCC patients with FGFR2 fusions/rearrangements. No statistically significant differences were observed in efficacy outcomes between futibatinib and pemigatinib, although numerical trends favored futibatinib. Molecular detail such as improved activity against co-mutated tumours and resistance mutations may explain such trends. [Table: see text]

e16168 Background: Several fibroblast growth factor receptor (FGFR) inhibitors have been recently approved or are in development for the treatment of cholangiocarcinoma (CCA) with FGFR2 fusions/rearrangements (f/r), such as the ATP-competitive inhibitors pemigatinib and infigratinib (FDA-approved in 2020/2021) and the covalent inhibitor futibatinib, which has shown efficacy in a pivotal phase 2 trial. To inform future evaluations of the impact of these agents in clinical practice, and understand other existing gaps in care, we investigated the characteristics and clinical management of patients with CCA and FGFR2 f/r prior to 2021. Methods: This real-world, retrospective cohort study used de-identified, patient-level electronic health records data from Cancer Treatment Centers of America (CTCA) to identify adults with a diagnosis of advanced intrahepatic CCA (iCCA) who received genomic testing between 2013-2021. Clinical/demographic characteristics, time to genomic testing, treatment patterns, and outcomes of patients with and without FGFR2 f/r were described. Results: 23 patients with FGFR2 f/r and 88 with FGFR wild-type (wt) iCCA were identified. Compared to FGFR wt, FGFR2 f/r had a higher proportion of female (65.2 vs 45.5%) and Black (39.1 vs 18.2%) patients (Table). Mean age at diagnosis was ̃60 y and >60% were diagnosed with stage 4 disease in both cohorts; 91.3% of f/r and 78.4% of wt patients had an ECOG PS 0/1. Median time from diagnosis to genomic testing was ̃5 mo; upon entry to CTCA, median time to testing was <2 mo. 17/23 patients in the f/r cohort had FGFR2 fusions (4 BICC1, 13 other). Three FGFR2 f/r patients received an FGFR inhibitor (pemigatinib) as next treatment after testing in 2020. A trend towards longer median overall survival in the f/r vs wt group (24.5 vs 17.8 mo), and a correlation of survival with ECOG PS were observed. Conclusions: This analysis provides insight into the real-world characteristics, clinical management and outcomes among patients with iCCA and FGFR2 f/r, predominantly prior to the introduction of FGFR inhibitors, providing a baseline for further study as the treatment landscape evolves. Of note, the time lag between diagnosis and genomic testing before entry to CTCA underlines the need for earlier testing to guide optimal therapy in clinical practice. [Table: see text]

7043 Background: Real-world studies have shown that persistence with intravenous (IV) and subcutaneous (SC) hypomethylating agents (HMAs) among patients (pts) with higher-risk myelodysplastic syndromes (MDS) is poor, with over one-third of treated pts receiving <4 cycles or having a ≥90-day gap in therapy, despite recommendations for at least 4-6 cycles to elicit response in absence of progression/unacceptable toxicity. Survival outcomes have also been shown to be worse, and direct medical costs higher, among HMA non-persistent vs persistent pts. We explored factors associated with early discontinuation of HMA therapy in this population. Methods: This was a retrospective cohort study among pts from the 2010-2016 SEER-Medicare linked database with a diagnosis of refractory anemia with excess blasts (RAEB; a surrogate for higher-risk MDS) from 2011-2015. Included pts had to have received HMA therapy and have ≥12 months’ continuous follow-up after diagnosis. Discontinuation was defined as stopping HMA therapy before 4 cycles. Multivariable logistic regression was used to assess predictors of HMA discontinuation. Results: In total, 664 pts with RAEB and treated with HMAs were included. Overall, 193 (29%) discontinued before 4 cycles; of these, 91 (47%) discontinued after 1 cycle, 57 (30%) 2 cycles, and 45 (23%) 3 cycles. Compared with pts continuing for ≥4 cycles, pts discontinuing before 4 cycles were generally older and more likely to be single/separated/divorced/widowed, have more comorbidities, and have poor performance status (PS) (Table). These trends were most pronounced among pts discontinuing HMA therapy after only 1 cycle vs ≥4 cycles (Table). In multivariable analysis, age 71-75 vs ≥80 y (odds ratio [OR] 0.556, p=0.017) and poor PS (OR 1.585, p=0.019) remained significant predictors of HMA discontinuation. Among treatment-related factors, the most statistically significant association with HMA discontinuation was observed for GCSF use (OR 0.453, p<0.001). Number of pills/day was not a predictor of HMA discontinuation (OR 1.009, p=NS). Conclusions: In this real-world study, almost one-third of RAEB pts treated with IV/SC HMAs discontinued before 4 cycles, with almost half of these pts discontinuing after only 1 cycle. Predictors of HMA discontinuation included older age and poor PS. Novel approaches are needed to improve persistence with HMA therapy, particularly among these higher-risk groups.[Table: see text]

Introduction: Hypomethylating agents (HMAs) are recommended as standard of care treatment for patients with higher-risk myelodysplastic syndromes (MDS); however, intravenous (IV) and subcutaneous (SC) administration of HMA therapy has been associated with additional patient burden. In July 2020, the HMA oral decitabine and cedazuridine (DEC-C) was approved by the US Food and Drug Administration (FDA) for the treatment of MDS, as an alternative to IV or SC HMAs. This study reports initial results evaluating DEC-C and IV/SC HMA treatment patterns and population characteristics among MDS patients in a real-world setting. Methods: This retrospective observational study utilized the IQVIA PharMetrics® Plus database which comprises adjudicated claims for more than 190 million unique patients across the US. Adults with ≥1 claim for HMAs between July 1, 2020 and November 30, 2021, and continuous enrollment for 6-months prior to and ≥1-month following the index date were included. Patients newly initiating HMA therapy were identified, where index was the date of the first claim for DEC-C (DEC-C-new cohort) or IV/SC HMA therapy (IV/SC-new cohort), and patients had no claims for HMA therapy in the prior 6 months; a third cohort including all patients initiating DEC-C as either new HMA therapy or switching from IV/SC HMAs was also identified, where index was the date of first claim for DEC-C (DEC-C-all cohort). Patients in the IV/SC-new cohort also had to have ≥1 diagnosis codes for high-grade MDS lesions and/or refractory anemia with excess blasts. Patients had a variable follow-up period of up to 1-year post-index and were followed through December 31, 2021. Demographic/clinical characteristics and treatment patterns were evaluated across the 3 cohorts according to HMA therapy. Results: Of 208 patients meeting inclusion criteria, 90 initiated DEC-C (DEC-C-all) and 118 initiated IV/SC HMAs (IV/SC-new) during the study period; 59 patients newly initiated HMA therapy with DEC-C (DEC-C-new). Demographic and clinical characteristics were similar across the 3 cohorts (Table), with no statistically significant differences observed between the DEC-C and IV/SC cohorts newly initiating HMA therapy. Overall, the proportion of males was higher (vs females) across the DEC-C-all, DEC-C-new, and IV/SC-new cohorts (61.1%, 62.7%, and 53.4%, respectively), and most patients were aged ≥55 years (93.4%, 91.5%, and 80.4%; median age 65, 67, and 64 years, respectively). All 3 groups had high levels of comorbidity, with mean Charlson Comorbidity Index (CCI) scores of 3.4, 3.3, and 3.1, respectively, and 27.8%, 27.1%, and 24.6% having CCI scores ≥5. Across the DEC-C-all, DEC-C-new, and IV/SC-new groups, common comorbidities included malignancy (58.9%, 55.9%, and 46.6%, respectively), chronic pulmonary disease (25.6%, 27.1%, and 22.9%) and congestive heart failure (20.0%, 15.3%, and 17.8%). In all groups, some patients had a diagnosis of acute myeloid leukemia (AML) during the pre-index period (20.0%, 10.2%, and 21.2%, respectively), and a small proportion received hematopoietic stem cell transplantation (HSCT) pre-index (6.7%, 1.7%, and 1.7%). Red blood cell transfusions were reported in 57.8%, 54.2%, and 53.4%, and platelet transfusions in 28.9%, 25.4%, and 22.9%, for the DEC-C-all, DEC-C-new, and IV/SC-new groups, respectively. Among patients with ≥6-months continuous enrollment post-index, mean number of HMA cycles of therapy (based on number of claims) over the 6-months post-index were similar (4.1, 4.1, and 4.2 cycles in the DEC-C-all, DEC-C-new, and IV/SC-new cohorts, respectively). Conclusions: To our knowledge, this study provides the first real-world data on treatment patterns and characteristics among MDS patients initiating oral DEC-C. Characteristics were similar among patients initiating DEC-C and IV/SC HMAs; data also suggest ongoing off-label use of HMAs post-HSCT transplant and in AML. The similar number of HMA claims between groups suggests comparable compliance with oral therapy at home vs IV/SC treatment in the clinical setting, with a possible advantage of DEC-C in reducing the treatment burden associated with existing IV/SC HMA therapy. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

4097 Background: In FOENIX-CCA2 (NCT02052778), a pivotal phase 2 study among iCCA patients (pts) with FGFR2 fusions/rearrangements, the highly selective, irreversible FGFR1–4 inhibitor futibatinib demonstrated a confirmed objective response rate of 41.7%, with a 9.7-month median duration of response. Adverse events were manageable with dosing modifications that did not adversely impact on response. We report outcomes for the preplanned analysis of Patient-Reported Outcomes (PROs) during futibatinib treatment as a secondary objective of FOENIX-CCA2. Methods: Pts enrolled in FOENIX-CCA2 had locally advanced/metastatic unresectable iCCA with FGFR2 fusions/rearrangements, ≥1 prior line of therapy (including gemcitabine/cisplatin) and ECOG PS 0-1. Pts received oral futibatinib 20 mg continuous QD dosing per 21-day cycle. PRO measures included EORTC-QLQ-C30 (1 global health, 5 functional, 9 symptom scales), EQ-5D-3L, and EQ visual analogue scale (VAS). PROs were collected at screening, cycles 2 and 4, every 3 cycles thereafter, and end of treatment. PRO data were evaluated up to cycle 13, the last visit before data were missing for >50% of the PRO population (PRO primary assessment time point). Results: 92/103 (89.3%) pts enrolled had PRO completion data at baseline and a minimum of 1 follow-up assessment (median age 58 y, 56.5% female), with 48 pts having PRO data at cycle 13. At baseline, mean (SD) EORTC QLQ-C30 global health status score was 70.1 (19.4) and EQ VAS score 71.7 (20.3). Mean EORTC QLQ-C30 global health status scores were maintained from baseline to cycle 13, corresponding to 9.0 months on treatment, with no clinically meaningful (≥10-point) changes in individual functional measures (Table). EORTC QLQ-C30 scores across individual symptom measures were also stable from baseline through cycle 13; only constipation showed an average of 10.0-point worsening at only cycle 4. Mean EQ VAS scores were sustained from baseline to cycle 13 (mean change ranging -1.8 to +4.8 across cycles), with values maintained within the population norm range from across 20 countries. Conclusions: Quality of life data from the phase 2 FOENIX-CCA2 trial show that physical, cognitive and emotional functioning, and overall health status were maintained among pts with advanced iCCA receiving futibatinib. Clinical trial information: NCT02052778. [Table: see text]

Introduction: Hypomethylating agents (HMAs) are standard of care treatment for patients with higher-risk myelodysplastic syndromes (HR-MDS) who are ineligible for stem-cell transplantation or intensive chemotherapy. Until recently, approved HMAs included intravenous or subcutaneous azacitidine and decitabine, which should be administered for a minimum of 4-6 cycles to elicit response in the absence of progression or unacceptable toxicity. In real-world clinical practice, underutilization of HMA therapy has been documented; however, prior estimates have utilized data preceding 2016. The study objectives were to understand recent treatment utilization and characteristics among patients newly diagnosed with HR-MDS in the United States (US).

Myelodysplastic syndromes are hematological malignancies characterized by ineffective hematopoiesis and a high risk of progression to acute myeloid leukemia. Hypomethylating agents (HMAs), azacitidine and decitabine, are standard of care therapy for higher-risk myelodysplastic syndromes. However, outcomes reported for real-world studies fall short of those achieved in clinical trials. We conducted a targeted literature review exploring real-world utilization, persistence and outcomes with intravenous and subcutaneous HMA therapies to better understand barriers to achieving optimal outcomes in clinical practice. The potential benefits of oral HMA therapy were also explored. Underutilization and poor persistence with HMA therapy are associated with suboptimal outcomes, highlighting the need for approaches to improve utilization and persistence, so that patients achieve the optimum benefit from HMA therapy.

Purpose To evaluate which side effects of chemotherapy are considered most burdensome by patients with cancer, identify which health care professionals pay most attention to symptoms associated with chemotherapy-induced myelosuppression (CIM) from the patient perspective, and capture the “patient voice” describing how CIM impacts their daily lives. Participants and Methods Online survey of participants with breast, lung, or colorectal cancer who had received chemotherapy within the past 12 months and experienced ≥1 episode of CIM in the past year. Participants were asked to answer close-ended questions and provide qualitative responses to: “In your own words, please describe how side effects from myelosuppression have impacted your life.” Results Among 301 survey participants, fatigue was the most frequently reported side effect of chemotherapy; 55% of participants rated fatigue as highly bothersome (9 or 10 on a 1–10 scale of “bothersomeness”). Participants rated symptoms associated with CIM, including fatigue, weakened immune system (infections), bleeding and/or bruising, and shortness of breath, as being as bothersome as other side effects of chemotherapy, including alopecia, neuropathy, and nausea/vomiting. Overall, 24–43% of participants thought that CIM and its symptoms had a negative impact on their daily lives, including their ability to complete tasks at home and work, and to socialize. Qualitative responses supported these findings; participants highlighted that CIM-related symptoms, particularly fatigue and fear of infections, affected their ability to be physically active, complete work, or continue meaningful relationships with friends and family. Conclusion Participants described a real-world impact of CIM that often isolates them from family and friends, and means that they are unable to work or perform tasks of daily living. Using measures that help patients to recognize and communicate the signs and symptoms of CIM might increase the likelihood of maintaining daily lives as close to normal as possible, during and after chemotherapy treatment.

Chemotherapy-induced myelosuppression (CIM) is one of the most common dose-limiting complications of cancer treatment, and is associated with a range of debilitating symptoms that can significantly impact patients’ quality of life. The purpose of this study was to understand patients’ perspectives on how the side effects of CIM are managed in routine clinical practice. An online survey was conducted of participants with breast, lung, or colorectal cancer who had received chemotherapy treatment within the past 12 months, and had experienced at least one episode of myelosuppression in the past year. The survey was administered with predominantly close-ended questions, and lay definitions of key terms were provided to aid response selection. Of 301 participants who completed the online survey, 153 (51%) had breast cancer, 100 (33%) had lung cancer, and 48 (16%) had colorectal cancer. Anemia, neutropenia, lymphopenia, and thrombocytopenia were reported by 61%, 59%, 37%, and 34% of participants, respectively. Most participants (79%) reported having received treatment for CIM, and 64% of participants recalled chemotherapy dose modifications as a result of CIM. Although most participants believed their oncologist was aware of the side effects of CIM, and treated them quickly, 30% of participants felt their oncologists did not understand how uncomfortable they were due to the side effects of CIM. Overall, 88% of participants considered CIM to have a moderate or major impact on their lives. The data highlight that despite the various methods used to address CIM, and the patient-focused approach of oncologists, the real-world impact of CIM on patients is substantial. Improving communication between patients and health care providers may help improve patients’ understanding of CIM, and foster shared decision-making in terms of treatment. Additional insights from patients should be obtained to further elucidate the totality of life burden associated with CIM. This study looked at people with cancer who received chemotherapy and developed a condition where their bone marrow activity was reduced, called myelosuppression. This meant they had fewer red blood cells that carry oxygen around the body, white blood cells that help fight infections, and platelets that help the blood to clot. The researchers wanted to understand how chemotherapy-induced myelosuppression affects peoples’ lives and their cancer treatment, and people’s experiences of treatment for myelosuppression. Overall, 301 people in the USA with breast, lung, or large bowel (colorectal) cancer completed an online survey. They had all received chemotherapy in the last year, and had myelosuppression at least once during their treatment. The survey showed that around 8 in 10 people (79%) had to be treated for myelosuppression, and around 7 in 10 people (73%) felt they received treatment for myelosuppression quickly. Chemotherapy was delayed, reduced, or stopped because of myelosuppression in around 6 in 10 people (64%). Around 3 in 10 people (30%) felt their oncologist did not understand the discomfort that myelosuppression caused them, and around 9 in 10 people (88%) felt that myelosuppression made their quality of life worse. The researchers concluded that because myelosuppression impacts peoples’ lives and their ability to keep receiving chemotherapy to treat their cancer, effective prevention and treatment for this condition are important. Better communication between people and their health care teams could help them to understand how people experience myelosuppression and make plans for treatment together.

e19300 Background: Myelosuppression is a common side effect of chemotherapy (CT) that can compromise patient (pt) and economic outcomes. To evaluate the overall burden of myelosuppression, a longitudinal, patterns of care analysis was conducted among pts with SCLC treated with CT in routine clinical practice. Methods: Data were obtained from Providence St. Joseph Health electronic medical records between Jan 2016 and Dec 2019. Hematologic adverse events, treatment patterns, and hospital-based healthcare resource utilization and costs were assessed during the 12 months from first diagnosis of SCLC in pts who had CT-induced grade 3/4 myelosuppression in 1st or 1st/2nd/3rd-line (1/2/3L) treatment settings. Descriptive statistics were utilized to summarize key findings. Costs of care were calculated from actual treatment costs for inpatient, outpatient, and emergency room services after first diagnosis and treatment with CT. Professional billing was not included due to variability in physician employment by the system. Results: 347 pts were eligible for analysis; mean age (SD) was 66 (9.0) years, 49% were female, and 89% were Caucasian. Prominent comorbidities included chronic obstructive pulmonary disease (52%), diabetes (23%), and peripheral vascular disease (20%). 264 pts (76%) received 1L treatment only, while an additional 83 pts (24%) had both 1L and 2/3L treatment. Of 339 evaluable pts with longitudinal laboratory data, grade 3/4 cytopenias were reported as follows: 45%, neutropenia; 41%, anemia; and 25%, thrombocytopenia. 43% and 15% of pts received red blood cell or platelet transfusions, respectively. 49% of pts received prophylaxis (6%) or treatment (43%) with G-CSF, and 4% of pts were treated with erythropoiesis-stimulating agents. Average total costs of care (post initial-diagnosis and treatment) for pts without grade 3/4 hematologic events (n = 110) were $67,802 per pt throughout the 12 months’ follow-up. On average, annual per pt costs for those with grade 3/4 hematologic events were $131,047 for neutropenia, $95,954 for anemia, and $90,053 for thrombocytopenia. Conclusions: A large and meaningful proportion of pts had grade 3/4 myelosuppression with annual incremental associated costs per pt ranging from $22,251 for pts with thrombocytopenia to $63,245 for pts with neutropenia. Despite the availability of protocols of care and various rescue treatments, CT-induced myelosuppression places a significant real-world burden on pts and the healthcare system.

e19299 Background: Research into the real-world impact of chemotherapy (CT)-induced myelosuppression on patients’ lives is limited. This study aimed to investigate the impact of CT-induced myelosuppression on patients with lung, breast, or colorectal cancer (CRC). Methods: Following Institutional Review Board approval to proceed with exception, a survey of participants identified from an online U.S. patient panel was conducted in Nov/Dec 2019. Participants who had been treated with CT in the past year and experienced ≥1 episode of myelosuppression (‘a decrease in bone marrow activity resulting in the reduced production of blood cells’) were eligible for participation. The survey was administered with predominantly close-ended questions, and lay definitions of key terms were provided to aid response selection. Descriptive statistics were used to summarize key findings. P values were calculated using the Chi-square test. Results: 301 participants completed the online survey (breast cancer, n = 153 [51%]; lung cancer, n = 100 [33%]; CRC, n = 48 [16%]). Most participants were aged > 40 years, 60% were female, 60% were currently employed, and 75% had been diagnosed with cancer within the last 3 years. Anemia, neutropenia, lymphopenia, and thrombocytopenia were reported by 61%, 59%, 37%, and 34% of participants, respectively. Fatigue was the most commonly noted side-effect of CT (reported by 72% of participants), with 55% of participants rating it as highly bothersome (9 or 10 on a 1–10 scale of ‘bothersomeness’). Most participants (89%) considered myelosuppression to have a moderate or major impact on life (major life impact, 40%; moderate life impact, 49%; minor life impact, 12%). Patient-reported impact of myelosuppression was significantly higher among participants aged < 50 years vs those aged ≥50 years (p = 0.01); however, no significant differences were observed when participants were stratified by sex, employment status, comorbidities (depression, diabetes, hypertension), or type of cancer. Significantly more participants with fatigue, considering themselves to have a weakened immune system, or noticing easy bruising/bleeding reported a major life impact vs those without these side effects (44% vs 27%, 52% vs 26%, and 50% vs 34%, respectively; all p < 0.01). Conclusions: These data provide further insights into the substantial real-world patient burden of symptoms arising from CT and associated with myelosuppression. Preventing or proactively managing CT-induced myelosuppression could have a major impact on patients’ quality of life.