1L Therapy Research Articles

Real-world use of biologics and its association with outcomes in RAS wild-type (WT) left-sided metastatic colorectal cancer (mCRC) in Canada.

56 Background: The use of biologics in combination with chemotherapy early in the course of treatment in mCRC improves outcomes, but whether this approach is uniformly adopted in clinical practice is unclear. This study aims to describe biomarker testing, treatment patterns, and survival of RAS WT, left-sided mCRC patients in a real-world population. Methods: We performed deterministic linkages with population-based data sources, including the cancer registry, pharmacy data, electronic medical records, and vital statistics to identify all patients who were diagnosed with RAS WT, left-sided mCRC, and treated with first-line (1L) combination systemic therapy from 2014 to 2019 in Alberta, Canada. Patients were followed until December 31, 2020. Results: Of 2,721 patients with left-sided mCRC, 1,375 were referred and received systemic therapy, 977 underwent RAS testing prior to or within 30 days of initiating 1L treatment, and 420 were found to be RAS WT. Among them, 320 were treated with 1L combination systemic therapy: FOLFOX/CAPOX/FOLFIRI (n=204), panitumumab (pani) with doublet chemotherapy (n=64), or bevacizumab (bev) with doublet chemotherapy (n=52). The interval from diagnosis to RAS test results was 38 (IQR 24-61) days. Only 207 (65%) and 125 (39%) of the 320 1L-treated patients reached 2L and 3L therapy, respectively. Median overall survival based on the different 1L regimens are summarized. Conclusions: Many real-world patients with mCRC were not exposed to biologics as part of their front-line treatment. There is a need to enhance RAS testing in 1L as 29% of patients were not tested, despite recommendations from guidelines. Because attrition across lines of therapy is high in mCRC, the opportunity to receive and benefit from biologics in later lines of therapy may be importantly reduced. [Table: see text]

Health-related quality of life (HRQoL) impact of lenvatinib (len) plus pembrolizumab (pembro) versus len plus placebo (pbo) as first-line (1L) therapy for advanced hepatocellular carcinoma (aHCC): Phase 3 LEAP-002 study.

506 Background: In LEAP-002 (NCT03713593), len + pembro achieved a median OS of 21.2 mo vs 19.0 mo with len + pbo with manageable safety in both arms in 1L aHCC, although the significance thresholds for OS and PFS were not met. We present here the results of prespecified exploratory patient (pt)-reported outcomes (PROs). Methods: 794 pts were randomized. PROs were assessed by EORTC QLQ-C30, EuroQol-5D5L (EQ5D-5L), and EORTC QLQ-HCC18 questionnaires. Analysis population for HRQoL endpoints included pts who received ≥1 dose of study Tx and completed ≥1 HRQoL assessment. Least squares mean (LSM) score changes from baseline (BL) to wk 27 were compared using a constrained longitudinal data analysis model (covariates: Tx, time, Tx by time interaction, and stratification factors). Kaplan-Meier method was used to estimate time to deterioration (TTD, time to 1st onset of ≥10 [out of 100] deterioration from BL in a given scale or subscale/confirmed by a 2nd adjacent ≥10 deterioration from BL) for EORTC QLQ-C30 global health status (GHS)/QoL, physical functioning (PF), and EORTC QLQ-HCC18 abdominal swelling, pain and fatigue, as reported by pts. Stratified Cox proportional hazards model was used to assess the magnitude of the Tx difference (HR) between arms in TTD. Results: Compliance with PRO assessments was >91% from BL until wk 27 in both arms. From BL to wk 27, LSM changes in GHS/QoL, PF, role functioning (RF), QLQ-HCC18 functional/domain scores and EQ5D-5L VAS were generally similar between the two arms (Table). Treatment with len + pembro delayed deterioration of patient-reported quality of life vs len + pbo (median TTD, 11.5 vs 4.3 mo; HR, 0.80; 95% CI, 0.65-0.98). LSM score difference (95% CI) was 0.5 (-2.5, 3.4) for GHS/QoL, -1.7 (-4.5, 1.1) for PF, -1.0 (-4.9, 2.9) for RF, 1.0 (-2.2, 4.3) for abdominal swelling, 2.0 (-1.2, 5.2) for fatigue, 2.0 (-1.0, 5.0) for pain, and 0.6 (-2.0, 3.2) for EQ5D-5L VAS. Median TTD in QLQ-C30 PF (5.7 vs 9.1 mo; HR, 1.14; 95% CI, 0.93-1.41) and QLQ-HCC18 abdominal swelling (NR vs NR; HR, 1.19; 95% CI, 0.89-1.60) /fatigue (2.9 vs 2.8 mo; HR, 0.98; 95% CI, 0.81-1.19)/pain (9.6 vs 7.9 mo; HR, 0.93; 95% CI, 0.75-1.16) was similar between the arms. Conclusions: Len + pembro generally preserved HRQoL vs len + pbo in 1L for aHCC. Combined with efficacy and safety results from LEAP-002, these findings support continued development of len + pembro in HCC. Clinical trial information: NCT03713593 . [Table: see text]

Clinical and mutational profiles of microsatellite instability (MSI-H) in intrahepatic cholangiocarcinoma (iCCA).

607 Background: Microsatellite instability (MSI-H) and increased tumor mutation burden (TMB) have been associated with clinical benefit from immunotherapy. A small subset of patients with intrahepatic cholangiocarcinoma (iCCA) have microsatellite instability (MSI-H). Understanding their clinical outcomes and genomic landscape has been limited. These patients may derive clinical benefit from immunotherapy compared to chemotherapy. Methods: 7565 cases of iCCA underwent comprehensive genomic profiling of 324 genes (FoundationOne CDx). Prevalence of genomic alterations in cases with MSI-H were compared with MSI-low and MSS iCCA using Fischer’s exact test with Bonferonni correction. Clinical and pathological data were collected by retrospective chart review for patients with MSI-H/dMMR iCCA. Results: Among 7565 iCCA cases identified, 137 (1.8%) were MSI-H. Compared to MSS/MSI-low cases, MSS-H patients were more likely to be male and have Lynch syndrome. Median TMB was 21.7 (muts/Mb). MSI-H cases were enriched for genomic alterations (GA) in APC (13.9%), TP53 (59.9%), ARID1A (13.9%), and PRBM1 (37.2%). MSI-H cases had lower frequencies of previously identified, actionable iCCA drivers such as FGFR2 fusions (0% v 9%, p=NS), IDH1 (3.7% v 14.5%, p<0.0001) and IDH2 (0% v 4.1%, p=0.007). Compared to MSS/MSI-low, MSI-H cases had higher GA in PIK3CA (16.8% v 6.6%, p=<0.0001), PTEN (10.9% v 2.8%, p=<0.0001), and BRCA2 (10.2% v 2%, p=<0.0001). MSI-H cases had lower GA in CDKN2A (24.1% v 30.9%, p=0.09) and MTAP loss (3.4% v. 15.5%, p<0.0001). Five patients were identified with dMMR/MSI-H iCCA out of 974 patients at a single institution (0.5%). Median age at diagnosis was 53 years (range 46-70) and 83% were male (n=4). Two patients had resectable disease at time of diagnosis. TMB range was 20-29 (muts/Mb). Patients had 4-6 co-mutations on average with the most common GA being TP53, ARID1A and CDKN2A. One patient had Lynch syndrome with germline alteration of MLH1 gene and one patient had a germline BRCA mutation. One patient was noted to have FGFR2 rearrangement. Gemcitabine/Cisplatin was given to 3 of 6 patients as first-line (1L) therapy, with median progression free survival of 4 months. One hundred percent of patients received immunotherapy (IO) as first or second-line (2L) therapies. Patients receiving IO in the 1L had responses ranging from 4 to 9 months. Three patients have ongoing responses. Median overall survival ranged from 12 months to >18 months. Two patients presented with CNS involvement and did not respond to immunotherapy-based regimens. Conclusions: MSI-H represents a small subset of patients with iCCA. High-TMB noted amongst MSI-H iCCA. Currently, MSI testing is not universally performed and may be necessary to identify and best treat these patients. These findings support the development of personalized immunotherapy treatment strategies for this distinct patient population.

Randomized, global, phase 3 study of tislelizumab (TIS) + chemotherapy (chemo) versus placebo (PBO) + chemo as first-line (1L) treatment for advanced or metastatic esophageal squamous cell carcinoma (ESCC) (RATIONALE-306): Non-Asia subgroup.

340 Background: TIS, an anti-programmed cell death protein 1 (PD-1) antibody, + chemo as 1L therapy demonstrated statistically significant and clinically meaningful improvement in overall survival (OS) vs PBO + chemo in patients with advanced or metastatic ESCC (hazard ratio [HR] 0.66 [95% confidence interval (CI) 0.54, 0.80]; P< 0.0001), with a manageable safety profile, at interim analysis of the phase 3, double-blind RATIONALE-306 study (NCT03783442). Here, we report data from the non-Asia subgroup (Europe, Northern America, and Oceania). Methods: Adults with advanced or metastatic ESCC, with no prior systemic treatment for advanced disease were randomized 1:1, (stratified by region, prior definitive therapy, and investigator [INV]-chosen chemo) to receive TIS 200 mg intravenously (IV) once every 3 weeks (Q3W) (Arm A) or PBO IV Q3W (Arm B), with platinum + fluoropyrimidine, or platinum + paclitaxel until disease progression by INV per RECIST v1.1, intolerable toxicity, or withdrawal. The primary endpoint was OS in the intent-to-treat population. Secondary endpoints included: progression-free survival (PFS), objective response rate (ORR), and duration of response (DoR) by INV per RECIST v1.1; OS in the programmed death-ligand 1 score ≥10%; and safety. Results: Of 649 randomized patients, 163 (25.1%) were from the non-Asia subgroup (Arm A, n = 83; Arm B, n = 80). At data cutoff (Feb 28, 2022), the median study follow-up time in the non-Asia subgroup was 16.0 months (mo) in Arm A vs 8.4 mo in Arm B. OS (median 16.3 vs 9.0 mo; unstratified HR 0.66 [95% CI 0.45, 0.96]) and PFS (median 7.7 vs 5.5 mo; unstratified HR 0.59 [95% CI 0.41, 0.83]) were improved in Arm A vs Arm B, respectively. Arm A had higher ORR (61.4% vs 41.3%, odds ratio 2.27 [95% CI 1.21, 4.25]) and longer median DoR (7.1 mo [95% CI 5.6, 9.6] vs 5.7 mo [95% CI 3.8, 8.3]) than Arm B. More patients in Arm A vs Arm B experienced ≥1 treatment-related adverse event (TRAE; 94.0% vs 88.5%), serious TRAEs (25.3% vs 17.9%), and discontinuation due to treatment-emergent AEs (42.2% vs 35.9%, respectively). Similar proportions of patients in Arm A vs Arm B had ≥grade 3 TRAEs (56.6% vs 52.6%), and TRAEs leading to death (1.2% vs 1.3%), respectively. Conclusions: In the non-Asia subgroup, 1L TIS + chemo showed a clinically meaningful improvement in OS vs PBO + chemo in patients with advanced or metastatic ESCC, with a manageable safety profile, consistent with published results in the overall population. Clinical trial information: NCT03783442 .

Real-world outcomes with front-line doublet versus triplet chemotherapy in advanced gastroesophageal adenocarcinoma.

313 Background: Current guidelines recommend an upfront cytotoxic doublet with or without targeted therapy or immunotherapy for the management of patients with advanced gastroesophageal adenocarcinoma (aGEA).While evidence for the superiority of combination chemotherapy over single agent chemotherapy has been well established, the comparison of two drug versus three drug regimens has been less definitive. This study analyzed a large real-world database to compare clinical outcomes between doublet and triplet approaches in the frontline setting. Methods: The nationwide de-identified Flatiron Health electronic health record (EHR)-derived database was reviewed for patients with aGEA treated with a first line (1L) cytotoxic doublet or triplet irrespective of combination targeted therapy between 2011 and 2022. Patients who received non-standard chemotherapy combinations or did not have a visit or medication order within 90 days of advanced stage diagnosis were excluded. Kaplan Meier and Cox proportional hazards models were used to compare overall survival outcomes between groups. Overall survival was considered as time from the 1L therapy to death with censoring for loss to follow up. Results: 5375 patients with aGEA who met inclusion criteria, 4415 (82%) received doublet chemotherapy and 960 (17%) received triplet in the 1L. Median OS (mOS) for those receiving a doublet was 11 months (95%CI 10-11) similar to those receiving a triplet (11 months, 95% CI 10-12). A Cox proportional hazards model controlling for potential confounding variables of gender, race, smoking status, disease site, as well as HER2 and PDL1 status did not show a significant difference in outcomes between the two groups (HR 0.9, 95%CI 0.8-1). A subgroup analysis comparing FLOT with FOLFOX/CapeOx demonstrated an improved mOS with FLOT (13 mo vs 10 mo; 95%CI 11-15 vs 9-10). This benefit was sustained in a multivariable analysis which demonstrated an increased risk of death with FOLFOX/CapeOX compared to FLOT (HR 1.2, 95% CI 1-1.4). Conclusions: Consistent with prior studies, this real-world study did not identify a significant difference in survival outcomes with 1L triplet compared to doublet chemotherapy in aGEA. When limiting analysis to modern chemotherapy regimens however this data does suggest that a survival benefit may exist with the use of FLOT when compared to FOFOX/CapeOX. This finding would need to be further evaluated in prospective trials incorporating immunotherapy and targeted therapy prior to widespread recommendation.

Exploring real-world outcomes with nivolumab plus chemotherapy in patients with advanced gastroesophageal adenocarcinoma.

325 Background: In the pivotal CheckMate-649 trial, nivolumab in combination with chemotherapy (nivo + chemo), compared with chemotherapy alone (chemo), demonstrated superior efficacy in patients with previously untreated, advanced gastric, gastro-esophageal junction, or esophageal adenocarcinoma (collectively: gastroesophageal adenocarcinoma). This study aimed to describe the real-world patterns of use and effectiveness of nivo + chemo for first-line (1L) treatment of advanced gastroesophageal adenocarcinoma. Methods: Patients aged ≥18 years, newly diagnosed with unresectable, advanced or metastatic, HER2-negative gastroesophageal adenocarcinoma, who received nivo + chemo or chemo only between 4/1/2021 and 5/31/2022 were identified from the Flatiron Health database. Chemo regimens included FOLFOX or CAPEOX. Patients were followed from index date (start of 1L therapy) until death, loss of data availability, or end of data abstraction (05/31/2022), whichever occurred first. Results: 352 patients with advanced or metastatic gastroesophageal adenocarcinoma were eligible for the analysis (N=158 in the nivo + chemo group and N=194 in the chemo group). Baseline demographic and clinical characteristics were balanced between groups. Median follow-up was 3.6 (interquartile range [IRQ]: 1.5–8.1) months for nivo + chemo and 4.4 (IQR: 1.9–7.6) months for chemo. 44.3% of patients in the nivo + chemo group and 36.1% in the chemo group had <3 months of follow-up available. Median overall survival (OS) from index date was not reached (95% confidence interval [CI]: 9.0 months, –) in the nivo + chemo group and was 10.0 (95% CI: 8.5, 11.6) months in the chemo group. 43 patients (27.2%) in the nivo + chemo group died during the study period compared with 64 patients (33.0%) in the chemo group. Median progression-free survival (PFS) from index date in patients who received nivo + chemo was 6.9 (95% CI: 5.6, 8.2) months compared to 5.5 (95% CI: 4.8, 7.4) months in patients who received chemo. Similar trends were observed in the subgroup of patients with a PD L1 combined positive score (CPS) ≥1, while data on the CPS ≥5 subgroup were not mature enough for meaningful analyses. Conclusions: The addition of nivolumab to chemotherapy for 1L treatment of advanced or metastatic gastroesophageal adenocarcinoma showed a trend towards survival benefit in the real-world setting. The study is ongoing. Subsequent analyses will capture a larger patient sample and longer follow-up, and describe PD L1 CPS-based subgroups. [Table: see text]

Prevalence of historical medical conditions or comorbidities with potential role in clinical decision making related to suitability of immuno-oncologic plus IV antiangiogenic therapy in newly diagnosed first-line unresectable hepatocellular carcinoma in the United States.

511 Background: Treatment landscape in advanced/unresectable hepatocellular carcinoma (uHCC) has been rapidly changing. In June 2020, the first immuno-oncologic (I/O) + IV anti-angiogenic regimen for uHCC was approved as first line (1L) treatment in the US. As with any new therapy, it is key to understand the prevalence of medical conditions listed in patient medical history/comorbidities that could potentially influence physician choice of 1L therapy in uHCC patients. Methods: We conducted a retrospective chart review study using Cardinal Health's Oncology Provider Extended Network (OPEN). US medical oncologists identified newly diagnosed adult uHCC patients initiating 1L systemic therapy from June 2020 to April 2022. Based on the warnings and precautions section of the US FDA labels, medical conditions reported as part of patient medical history or comorbidities [including gastrointestinal (GI) bleeding risk, chronic kidney disease, autoimmune disorders, thromboembolic events] were identified from patient medical records. Less suitable was defined as the occurrence of ≥ 1 medical condition/comorbidity reported in the medical record. All patient data were deidentified. Proportions of patients with the above medical conditions or with physician-reported record of an esophagogastroduodenoscopy (EGD) procedure to assess risk of bleeding were calculated. Results: In the cohort of 433 uHCC patients initiating 1L systemic therapy, majority were male 287 (66%), Caucasian 244 (56%) with average age of 64 years. At 1L initiation, majority of the patients were 333 BCLC Stage C (77%) and 316 (73%) had ECOG performance status of 0 or 1. Approximately 160 (37%) were Child-Pugh B, 99 (23%) had non-alcoholic steatohepatitis (NASH), 176 (41%) had Hep-C etiology (among those tested), and 294 (68%) had liver cirrhosis. Prior to therapy initiation, 254 (59%) received EGD within 3 months. In the overall cohort, 221 (51%) patients were reported to have at least one condition listed as medical history/comorbidity that could make them less suitable to receive I/O + IV anti-angiogenic regimen. Upper/lower GI bleeding risk and chronic kidney disease were reported in 164 (38%) and 64 (15%) patients, respectively. History of thromboembolic events and autoimmune disorders were reported in 50 (12%) and 22 (5%) of patients, respectively. Conclusions: A significant proportion of the newly diagnosed uHCC patients were found to have at least one condition listed as medical history/comorbidity that would make them potentially less suitable for I/O + IV anti-angiogenic regimen. Our findings reinforce the importance of medical history and co-morbidity assessment in uHCC patients prior to therapy selection to optimize benefit-risk ratio for each patient.

Healthcare Resource Utilization and Costs Among Commercially Insured Patients With Advanced or Recurrent Endometrial Cancer Initiating First-Line Therapy in the United States

Background: Endometrial cancer (EC) represents a substantial economic burden for patients in the United States. Patients with advanced or recurrent EC have a much poorer prognosis than patients with early-stage EC. Data on healthcare resource utilization (HCRU) and costs for patients with advanced or recurrent EC specifically are lacking. Objectives: To describe HCRU and costs associated with first-line (1L) therapy for commercially insured patients with advanced or recurrent EC in the United States. Methods: This was a retrospective cohort study of adult patients with advanced or recurrent EC using the MarketScan® database. Treatment characteristics, HCRU, and costs were assessed from the first claim in the patient record for 1L therapy for advanced or recurrent EC (index) until initiation of a new anti-cancer therapy, disenrollment from the database, or the end of data availability. Baseline demographics were determined during the 12 months before the patient’s index date. Results: A total of 7932 patients were eligible for inclusion. Overall, mean age at index was 61 years, most patients (77.3%) had received prior surgery for EC, and the most common 1L regimen was carboplatin/paclitaxel (59.1%). During the observation period, most patients had at least one healthcare visit (all-cause, 99.9%; EC-related, 82.8%), most commonly outpatient visits (all-cause, 91.4%; EC-related, 68.7%). The highest mean (SD) costs (US dollars) were for inpatient hospitalization for both all-cause and EC-related events ($8396 [$15,130] and $9436 [$16,784], respectively). Total costs were higher for patients with a diagnosis of metastasis at baseline than for those without a diagnosis of metastasis. Discussion: For patients with advanced or recurrent EC in the United States, 1L therapy is associated with considerable HCRU and economic burden. They are particularly high for patients with metastatic disease. Conclusions: This study highlights the need for new cost-effective treatments for patients with newly diagnosed advanced or recurrent EC.

Treatment Intensification Patterns and Utilization in Patients with Metastatic Castration-Sensitive Prostate Cancer.

Patients with mCSPC experience a longer overall survival with treatment intensification by addition of novel hormonal therapy (NHT) or docetaxel to androgen deprivation vs androgen deprivation alone. Real-world data report, however, that nearly half of mCSPC patients do not receive treatment intensification. In this study, treatment patterns and utilization of treatment intensification in mCSPC patients were described using the IQVIA Anonymized Patient Longitudinal Data, a dataset of fully adjudicated pharmacy and medical claims. Reports on first line (1L) treatment patterns were obtained for years 2015 to 2021. Medicaid, Medicare, Medicare part D, cash transactions, and commercial data were included for years 2012 to 2021. Nationwide, of 66,844 men with newly diagnosed mCSPC since 2015, on average 25% were prescribed NHT, and another 12% were prescribed chemotherapy. No differences were noted in treatment patterns based on U.S. regions and/or rural vs. urban communities. The disparity was observed in prescribing patterns between oncology and urology providers. Oncology providers prescribed 1L NHT on average 32% of the time, while urology providers did so 12% of the time. Furthermore, oncology providers prescribed chemotherapy on average 20% of the time, resulting in 52% of men with mCSPC receiving treatment intensification as 1L therapy. Patients' age group, community or health insurance did not account for the disparity between the 2 specialties. Both medical oncology and urology providers need to improve their treatment intensification efforts for men with mCSPC to increase their patients' overall survival.

Clinical Outcomes, Treatment and Testing Patterns in Patients with Advanced Non-Small Lung Cell Cancer with Epidermal Growth Factor Receptor Mutations: Results of the Romanian Cohort From a Multi-national Retrospective Chart Review (REFLECT)

"Background: REFLECT was a retrospective, non-interventional study conducted in eight countries, including eleven sites from Romania, on patients with advanced stage non-small cell carcinoma (NSCLC). Aim: To characterize clinical outcomes, treatments and the proportion of T790M EGFR mutation testing in patients with advanced non-small cell lung cancer (NSCLC) receiving first- or second-generation (1G/2G) epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs ) as first-line (1L) treatment in the Romanian cohort of an international study. Methods: Comprehensive data were retrieved from the medical records of ninety patients with EGFR-mutated advanced NSCLC treated with 1G/2G EGFR TKIs between January 2015 and June 2018. All analyses are descriptive. Results: The median age at lung cancer diagnosis in the Romanian cohort was 67.5 years, with 68% females. The distribution of EGFR TKIs was 50% erlotinib, 31% afatinib, and 19% gefitinib. First line treatment was stopped in 76 (84%) patients due to progression (79%), toxicities (3%), the patient’s decision (1%) or surgery (1%). The median progression- free survival on 1L treatment was 12.0 months (95% CI 10.3-15.6), and the median overall survival from the start of first line therapy was 26.4 months (95% CI 22.4-34.2). EGFR T790M mutation testing was performed on 69% of patients at the time of progression on 1L therapy, with 57% of patients testing positive. Second-line (2L) therapy was started in 63% of patients discontinuing 1L therapy. Third-line treatment was started in 50% of patients discontinuing 2L treatment. Conclusion: Survival results mirrored those of randomized trials. The suboptimal T790M testing rate (69%) underlines the importance of reflex testing procedures, while attrition rates on 1L (26%) emphasize the need for an upfront selection of the most effective treatments."

Factors associated with receipt of second-line recurrent or metastatic cervical cancer treatment in the United States: A retrospective administrative claims analysis

PurposeContemporary, real-world data on eligible patients receiving treatment following progression on first-line (1L) recurrent or metastatic cervical cancer (r/mCC) therapy are needed to inform treatment algorithms and identify potential gaps in the r/mCC care continuum. MethodsThis study estimated the prevalence and predictors of second-line (2L) r/mCC therapy among 1L-treated patients using the 2015–2020 IBM MarketScan® commercial claims database. Women ≥ 18 years diagnosed with cervical cancer and treated with first-line systemic therapies were identified and followed for 12 months from their 1L therapy end date. Women with claims for a new therapy after 60 days but no later than 365 days from the end of 1L treatment were identified as those who progressed and received 2L therapy for r/mCC. Descriptive statistics examined baseline cohort characteristics and multivariable logistic regression model examined the factors associated with receiving 2L treatment. ResultsWe identified 384 1L-treated patients with r/mCC with ≥ 12 months of follow-up post-1L treatment. During follow-up, over half (51.0 %) of the 1L-treated r/mCC patients received 2L treatment. Patients from the South and Midwest had a lower likelihood of receiving 2L treatment compared with those living in the Northeast (adjusted odds ratio [aOR] = 0.43; 0.23–0.84) and (aOR = 0.52; 0.28–0.95, respectively). Patients not treated with bevacizumab in 1L were also less likely to receive 2L therapy (aOR = 0.65; 0.43–0.99). ConclusionAdditional research and targeted outreach efforts are needed to understand geography-, population-, or practice-specific barriers impacting access to 2L therapy among patients with r/mCC.

138P Randomized phase III study of tislelizumab plus chemotherapy versus chemotherapy alone as first-line treatment for advanced non-squamous non-small cell lung cancer (nsq-NSCLC): RATIONALE-304 updated analysis

Interim analysis of the open-label phase 3 RATIONALE-304 study (NCT03663205) demonstrated clinical benefit of tislelizumab (TIS) plus chemotherapy (chemo) as first-line (1L) therapy in patients with advanced nsq-NSCLC vs chemo alone, with significantly improved progression-free survival (PFS) and a manageable safety profile. Here, we report the updated results.

160P COLUMBIA-1: A phase Ib/II, open-label, randomized, multicenter study of durvalumab plus oleclumab in combination with chemotherapy and bevacizumab as first-line (1L) therapy in metastatic microsatellite-stable colorectal cancer (MSS-mCRC)

Despite advances in the treatment of mCRC combining chemotherapy regimens with biologics, most patients (pts) still progress within 11 months of receiving 1L chemotherapy. Addition of novel therapies to the standard of care (SoC) to improve antitumor activity is urgently needed. The randomized part 2 of COLUMBIA-1 (NCT04068610) evaluated the safety and efficacy of combining SoC (bevacizumab [BEV] + FOLFOX) with the PD-L1 inhibitor durvalumab (D) and the anti-CD73 monoclonal antibody oleclumab (O).

132P Randomized phase III study of tislelizumab plus chemotherapy versus chemotherapy alone as first-line treatment for advanced squamous non-small cell lung cancer (sq-NSCLC): RATIONALE-307 updated analysis

Interim analysis of the open-label phase 3 RATIONALE-307 study (NCT03594747) demonstrated clinical benefit, including significantly improved progression-free survival (PFS) with a manageable safety profile, of tislelizumab (TIS) plus chemotherapy (chemo) as first-line (1L) therapy in patients (pts) with advanced sq-NSCLC vs chemo alone. Here, we report updated results.

Cost-consequence of abatacept as first-line therapy in Japanese rheumatoid arthritis patients using IORRA real-world data.

To investigate the cost-effectiveness of abatacept (ABA) as first-line (1L) therapy in Japanese rheumatoid arthritis (RA) patients using data from the Institute of Rheumatology, Rheumatoid Arthritis database. A decision-analytic model was used to estimate the cost per American College of Rheumatology response of at least 50% improvement (ACR50) responder and per patient in Clinical Disease Activity Index (CDAI) and Simplified Disease Activity Index (SDAI) remission from a Japanese healthcare payers' perspective over a 2-year time horizon. Clinical characteristics of patients on ABA-1L were matched with those of patients on ABA second or later line (2L+) or tumour necrosis factor inhibitor (TNFi)-1L directly or using propensity scores. Resource utilisation and medical costs were calculated from the Japan Medical Data Center claims database. Parameter uncertainty was addressed by sensitivity and subgroup analyses (age, treatment duration, Japanese version of Health Assessment Questionnaire [J-HAQ] score). Incremental costs per member per month (ΔPMPM) for ABA-1L versus TNFi-1L and ABA-2L+ were -1,571 Japanese Yen (JPY) and 81 JPY, respectively. For ABA-1L versus TNFi-1L, ΔPMPM by ACR50 response was -11,715 JPY and by CDAI and SDAI remission 11,602 JPY and 47,003 JPY, respectively. Corresponding costs for ABA-1L were lower for all outcome parameters versus those for ABA-2L+. Scenario analyses showed that ABA-1L was cost-effective over TNFi-1L in patients <65 years for any outcome. Furthermore, ABA-1L was cost-effective over ABA-2L+ for all outcomes in patients with age <65 years, disease duration <5 years and J-HAQ ≥1.5. ABA-1L demonstrated a favourable cost-effectiveness profile in RA patients, accruing savings for the Japanese healthcare payers.

Treatment Patterns and Outcomes in Relapsed/Refractory Mantle Cell Lymphoma

Background: Mantle cell lymphoma (MCL) is an uncommon B-cell lymphoma with heterogeneous clinical presentations and treatment response. Over the last two decades, the frontline therapy for MCL has evolved and we previously characterized this shift and the associated improvement in survival outcomes (Castellino, Blood Advances 2022). The evolved landscape of frontline therapy, as well as the emergence of new agents, may have impacted second-line (2L) treatment choice, response and survival. In this study we investigated the treatment patterns and survival outcomes for patients with R/R MCL treated with 2L therapy. Methods: Consecutive patients with newly diagnosed MCL from September 2002 through June 2015 were offered enrollment in the Mayo Clinic/University of Iowa Molecular Epidemiology Resource (MER). All participants were prospectively followed for disease relapse/progression, subsequent treatments, and death. Patients who initiated 2L therapy for R/R MCL through 2021 were included in this analysis. Clinical characteristics, 1L, and 2L therapies were abstracted from MER and medical records. Treatment outcomes were calculated from the start of 2L therapy. Event-free survival (EFS) was defined as time from 2L initiation to progression, retreatment, or death due to any cause. Overall survival (OS) was defined as the time from 2L initiation to death due to any cause. A spline plot was generated to visualize the hazard ratio (HR) for EFS and OS over time from the initiation of 2L treatment. Three eras were defined based on the timing of 2L treatment: 2003-2009 (Era 1), 2010-2014 (Era 2), and 2015-2021 (Era 3). Eras were chosen to align with approval of novel therapies. Results: Among a total of 343 MCL patients, with a median follow up of 7.6 years, 59 died without progression and 194 relapsed. Of those, 177 received 2L therapy and had complete treatment information available (N=58 in Era 1, N=71 in Era 2, N=48 in Era 3). At the time of 2L therapy, 127 (72%) patients had an age >60 years, 143 (81%) were male, 139 (79%) had stage III/IV disease, and simplified MIPI was low in 37 (34%), intermediate in 42 (39%), and high in 30 patients (28%; simplified MIPI missing in 68 patients). No statistical differences in age, sex, stage, or simplified MIPI were found among different eras. The patterns of 2L treatment by era, and previous 1L treatment, are shown in Figure 1. There were substantial heterogeneities in both 2L and 1L treatments across all eras. Notable changes in 2L treatment patterns were observed among different eras, likely related to drug availability and 1L treatment choices. Few to no patients received a Bruton's tyrosine kinase (BTK) inhibitor in 2L in Era 1 (N=0) and Era 2 (N=4; 6%), largely due to lack of availability, in contrast to Era 3 (N=21; 44%). The use of bendamustine-rituximab (BR) in 2L was minimal in Era 1 (N=2; 3%) and less in Era 3 (N=8; 17%) compared to Era 2 (N=26; 37%). High dose cytarabine use in 2L was higher in Era 1 (N=4; 7%) and Era 2 (N=4; 6%) compared to Era 3 (N=0). The percentage of patients who received autologous or allogeneic stem cell transplant appeared similar: Era 1 (N=5; 9%), Era 2 (N=10; 14%), and Era 3 (N=6; 13%). The median follow-up from 2L therapy in Eras 1-3 was 13.3, 8.7, and 4.2 years, respectively. The overall response rate to 2L therapy was 57%, 79% and 83%, respectively (complete response rate 30%, 52% and 51%, respectively). The estimated 2-year EFS rate was 21% (95% CI: 13-34) in Era 1, 39% (95% CI: 29-52) in Era 2, and 58% (95% CI: 44-75) in Era 3. The estimated 5-year OS rate was 31% (95% CI: 21-46) in Era 1, 38% (95% CI: 28-52) in Era 2, and 69% (95% CI: 56-86) in Era 3. The spline plot depicts a trend in decreased hazard in EFS and OS over time (Figure 2). For example, compared to 2L start in April 2012 (median 2L start date, reference point), 2L start in January 2008 and January 2017 had a HR for EFS of 1.6 and 0.8 respectively, and a HR for OS of 1.4 and 0.4, respectively. Conclusion: 2L therapy for MCL evolved with time and was likely affected by 1L treatment choice as well as the availability of treatment options at the time of need. The changes in 2L treatment correlated with improved EFS and OS, suggesting that treatment advances were associated with improved outcomes in patients with R/R MCL. Larger real-world studies are needed to further understand treatment patterns, changes with time, and the association with outcomes in R/R MCL, including 2L and subsequent lines of therapy. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Clinical Characteristics and Overall Survival Among Acute Myeloid Leukemia (AML) Patients with TP53 Gene Mutation (TP53m) or Chromosome 17p Deletion (17p del)

Introduction TP53m is observed in 5%-15% of newly diagnosed AML patients (pts) and represent a poor prognostic group that is highly refractory to available treatment, both intensive and non-intensive, including venetoclax-based therapies. Currently there are no established therapies specifically targeting TP53m in AML. Better understanding of the outcomes in TP53m AML pts with standard-of-care treatments can provide important insights for clinical management and drug development. Methods Adult (≥18 years [yrs]) pts with new AML diagnosis from January 1, 2014 to February 28, 2021 were included from the nationwide Flatiron Health electronic health record-derived de-identified database. Prior to first line (1L) therapy start, all pts had TP53m determined from molecular tests or 17p del identified by cytogenetic/fluorescent in situ hybridization. Pts who received prior anti-leukemic therapies (except hydroxyurea, oral etoposide) or who had concurrent malignancies were excluded. Pts receiving 1L therapy were divided into 3 cohorts: hypomethylating agents (HMA; azacitidine/decitabine) and venetoclax (Cohort A), intensive chemotherapy (Cohort B), or HMA without venetoclax (Cohort C). Median overall survival (mOS) was estimated using Kaplan-Meier method. Baseline and clinical characteristics can impact treatment choice and survival in each cohort. Multivariate Cox proportional hazards models (including age, time to 1L therapy, comorbidities, TP53m status and cytogenic risk level, presence of 17p del, secondary and therapy-related AML, healthcare practice type, ECOG score, and post-1L allogeneic stem cell transplantation [allo-SCT]) were used to compare OS among treatment cohorts. Results A total of 370 AML pts with either TP53m (n=124) or 17p del (n=166) or both (n=80) were included. Median age was 72 (range 24-84) yrs, and majority were male (59%) and white (69%). Most pts (85%) were from community oncology clinics. Overall median follow-up time for all pts was 6 (range 0-74) mos and was similar for the three cohorts (6, 7, and 5 mos for Cohort A, B, and C, respectively). Although cytogenetic risk category information was missing for more than one-third (34%) of pts, majority (65%) belonged to the ELN 2017 adverse cytogenetic risk category. Deletions in chromosomes 5, 7, or 17 were reported in 88% (n=324) of pts, with 68% having more than one deletion. Secondary AML was reported for 118 (32%) pts, of which 92 (78%) had prior myelodysplastic syndrome; 38 pts (10%) had therapy-related AML. Bone marrow (BM) blasts were ≤30%, 31-50%, and >50% in 41%, 24%, and 29% of pts, respectively. Treatment Cohort A, B, and C included 94 (25%), 135 (37%), and 141 (38%) unique AML pts, respectively. Pts in Cohort A and C were older (median 75 and 77 yrs vs 62 yrs for Cohort B) and had more comorbidities (65% and 60% vs 40% in Cohort B with at least one comorbidity). BM blast clearance post-1L was reported in 54% of pts (115/215) overall and 67% (38/57), 62% (68/110), and 19% (9/48), with median duration of blast clearance of 6.3, 6.9, and 5.4 mos for Cohort A, B, and C, respectively. Only 30 pts (8%) received allo-SCT (5%, 16%, and 3% in Cohort A, B, and C, respectively). Death during follow-up was reported in 80% (n=294) of pts with mOS of 7.3 mos (95% confidence interval [CI] 6.5-8.3). mOS estimate was 7.4 mos (95% CI 6.0-8.8) for Cohort A, 9.4 mos (95% CI 7.2-10.4) for Cohort B and 5.9 mos (95% CI 4.3-7.5) for Cohort C. Survival was much higher in pts receiving allo-SCT, which only few pts in each cohort received (Table). Addition of venetoclax to HMA (Cohort A) did not improve OS compared with HMA only (Cohort C) in an adjusted Cox model (adjusted hazard ratio [aHR]=0.9, 95% CI 0.7-1.3). In a similar analysis, no difference in OS was observed between Cohort A and B (aHR=0.9, 95% CI 0.6-1.4). Conclusions In this large cohort of AML pts with TP53m/17p del, poor OS is observed with current standard-of-care treatment options. Pts treated with venetoclax and HMA combination did not have significantly different OS compared with pts treated with HMA only or pts receiving intensive chemotherapy. Younger age, fewer comorbidities, and higher number of pts receiving allo-SCT could have influenced apparent longer OS in the intensive chemotherapy cohort that was no longer significant in an adjusted model. Despite recent advances, TP53m AML pts continue to experience poor outcomes highlighting the significant unmet medical need and the need for novel therapies. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Real-World Comparison of Time to Next Treatment for Patients with CLL Initiated on First-Line Treatment with Ibrutinib Versus Acalabrutinib

Introduction: Treatment guidelines recommend Bruton's tyrosine kinase inhibitors (BTKi) ibrutinib (once-daily) and acalabrutinib (twice-daily) as preferred regimens for chronic lymphocytic leukemia (CLL); however, there are no studies comparing the effectiveness of ibrutinib and acalabrutinib as first-line (1L) therapy in CLL. This study investigated time to next treatment (TTNT) for patients with CLL initiated on 1L ibrutinib or acalabrutinib in real-world (RW) clinical practice in the US. Methods: Specialty pharmacy electronic medical records from academic integrated care networks (11/21/2018-4/30/2022) were used to identify adults with CLL who initiated ibrutinib or acalabrutinib in 1L (index date) on or after the date of acalabrutinib approval for CLL (11/21/2019). A washout period of ≥12 months without antineoplastic agent use pre-index was required to confirm use as 1L therapy. Patients were excluded if there was concomitant use of another antineoplastic agent during the first 28 days post-index. Characteristics evaluated in the 12-month baseline period were compared between ibrutinib and acalabrutinib cohorts using t-tests for continuous variables and chi-square tests for categorical variables. TTNT was defined as the time from the index date to the initiation a next or additional treatment. Patients without a next/additional treatment were censored at death or end of data (4/30/2022). Patients with a within-class BTKi switch at any time post-index were censored at time of switch, as this may have indicated a switch due to tolerability rather than progression. Patients who added an anti-CD20 antibody or venetoclax to the BTKi within 180 days post-index were censored at time of add-on, as these may not have indicated overt disease progression but rather late initiation of a second anti-cancer agent as a 1L combination treatment strategy. Beyond 180 days, anti-CD20 or venetoclax add-ons were considered as a next/additional treatment. TTNT was described using Kaplan Meier curves and compared between ibrutinib and acalabrutinib using a Cox proportional hazards model adjusted for the following baseline variables: age, gender, region, race, year of index date, Quan-Charlson Comorbidity Index (Quan-CCI), chronic pulmonary disease (CPD), peripheral vascular disease, hypertension, atrial fibrillation (AF), metastatic cancer, use of corticosteroids, and use of antiplatelets. Results: Among 710 and 373 patients in the ibrutinib and acalabrutinib cohorts, respectively, mean age was 71.5 and 72.4 years (P=0.159) and 38.5% and 38.3% were female (P=0.971; Table). Mean baseline Quan-CCI score was similar for ibrutinib and acalabrutinib (3.1 vs 3.0; P=0.597); a higher proportion of patients in the ibrutinib cohort had CPD (13.6% vs 8.8%; P=0.024), peripheral vascular disease (7.8% vs 4.1%; P=0.022), and hypertension (41.4% vs 32.2%; P=0.003) at baseline, while AF was similar (7.0% vs 9.9%, P=0.098). Baseline corticosteroid use was lower in the ibrutinib cohort (14.5% vs 20.1%; P=0.018), but antiplatelet use was higher (7.0% vs 3.5%; P=0.017). Mean (median [range]) follow-up was 17.1 (18.1 [1.0-29.3]) months for the ibrutinib cohort and 12.5 (11.9 [1.0-29.1]) months for the acalabrutinib cohort. Four/710 (0.6%) patients in the ibrutinib cohort and 16/373 (4.3%) in the acalabrutinib cohort added an anti-CD20 antibody to the BTKi within 180 days and were censored at that point. Ten/710 (1.4%) and 8/373 (2.1%) patients added venetoclax to ibrutinib or acalabrutinib within 180 days and were censored at that point. The proportion of patients in the ibrutinib cohort who initiated a next or additional treatment was 5.9% relative to 7.5% for acalabrutinib. After adjusting for baseline characteristics, patients treated with acalabrutinib were 89% more likely to start a next or additional treatment than those treated with ibrutinib (hazard ratio = 1.89 [95% confidence interval] = [1.12, 3.13]; P=0.016; Figure). Results were similar when censoring anti-CD20 add-ons at any time (hazard ratio = 1.82 [95% confidence interval] = [1.08, 3.03]; P=0.025). Conclusions: In this large US RW study, patients with CLL treated with 1L acalabrutinib were significantly more likely to start a next treatment or add/intensify therapy than those treated with 1L ibrutinib. RW treatment patterns also suggest a higher propensity to add an anti-CD20 antibody to acalabrutinib versus ibrutinib in 1L CLL. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

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

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

Real-World Outcomes with First-Line Ibrutinib (Ibr) Versus Chemoimmunotherapy (CIT) in Patients with Chronic Lymphocytic Leukemia (CLL)/Small Lymphocytic Lymphoma (SLL): Final Analysis Results from the InformCLL Registry

Background: The therapeutic landscape for CLL/SLL has rapidly evolved with the introduction of novel agents such as Ibr. The informCLL registry (PCYC-1134; NCT02582879) is the largest US-based prospective, observational registry of patients (pts) initiating FDA-approved treatment for CLL/SLL in the era after approval of Ibr. Here, we report real-world (RW) outcomes in pts with CLL/SLL receiving first-line (1L) therapy, including comparison of 1L Ibr versus CIT, from the final analysis of informCLL. Methods: Pts with CLL/SLL who initiated FDA-approved treatment (within ±45 days of enrollment) were enrolled between 10/2015 and 6/2019. Pts were primarily enrolled from community-based practices (comprising 93% of sites). Data were collected for baseline characteristics, treatment patterns, and safety. Time to next treatment (TTNT) was estimated by Kaplan-Meier method and for comparison of outcomes with 1L Ibr versus CIT, by Cox proportional hazards regression analysis in weighted cohorts. Inverse probability of treatment weighting (IPTW) was performed to balance the baseline characteristics between cohorts. Adverse events (AEs) were evaluated using overall incidence and exposure-adjusted incidence rates (EAIRs). Results: Of the 1459 eligible pts enrolled, 854 were treated in the 1L setting (59%). In the overall 1L cohort, median age was 70 years (≥75 years in 33%); 90% had ECOG performance status of 0 or 1; 47% had Rai stage III/IV (among n=547 with Rai staging); median Charlson Comorbidity Index (CCI) score was 1 (range 0-12) with CCI ≥3 in 16%; median time from initial diagnosis to 1L treatment was 19 mo. FISH testing data were available in 57% of pts in the 1L cohort; among these pts, 12% had del(17p). The most common 1L therapies were Ibr (45%; single-agent Ibr in 43% of all 1L therapies) and CIT (43%: most commonly BR, 24%); immunotherapy was given in 11% while chemotherapy (0.9%) and other novel agents (0.7%) were rare. With a median follow-up of 31.8 mo in the 1L cohort, median TTNT was not reached (NR); estimated proportions of pts without next-line therapy (NLT) were 79% at 24 mo, 71% at 36 mo, and 64% at 48 mo. The 1L cohort included 383 pts treated with Ibr and 363 pts treated with CIT; median follow-up was 31.4 mo for the Ibr cohort and 34.3 mo for CIT. Compared with the CIT cohort, pts in the Ibr cohort were older, had longer time from diagnosis to treatment, were more likely to have a history of other malignancy, and were more likely to have del(17p) or TP53 mutation (Table). Baseline characteristics in the weighted cohorts were balanced. In the IPTW-adjusted cohorts, median TTNT was NR for Ibr and 56.5 mo for CIT; TTNT was improved with Ibr relative to CIT (hazard ratio 0.744; 95% CI, 0.563-0.981) (Figure). Estimated proportions free of NLT in the weighted Ibr cohort were 75% at 36 mo and 69% at 48 mo; rates in the weighted CIT cohort were 66% and 57%, respectively. Median duration of index treatment was 24.0 mo for 1L Ibr and 4.7 mo for CIT. In the Ibr cohort (n=383), serious AEs occurred in 144 pts (38%), most commonly (≥3% of pts) pneumonia (n=23; 6%) and atrial fibrillation (Afib; n=21; 5%); AEs led to discontinuation of Ibr in 135 pts (35%), most commonly Afib (n=19; 5%) and fatigue (n=12; 3%). In the CIT cohort (n=363), serious AEs occurred in 85 pts (23%), most commonly febrile neutropenia (n=13; 4%) and pneumonia (n=11; 3%). AEs led to discontinuation of CIT in 61 pts (17%), and no single AE term led to discontinuation in ≥3% of pts (most common was anemia, 2%). EAIRs per 100 pt-mo for serious AEs were 1.93 with Ibr and 4.55 with CIT. EAIRs per 100 pt-mo for AEs leading to discontinuation were 1.53 with Ibr and 3.09 with CIT. Conclusion: In this large RW registry of pts with CLL/SLL, results from IPTW-adjusted analysis showed that 1L Ibr was associated with longer TTNT than CIT, with sustained benefit up to 4 years of follow-up. Pts receiving 1L Ibr therapy tended to be older, more often had a history of other malignancy, and more often had high-risk genomic features (del(17p) or TP53 mutation among those tested) than pts treated with CIT. The spectrum and frequency of AEs observed with these 1L regimens appear consistent with data from clinical studies and other RW studies. When adjusted for exposure, rates of AEs leading to discontinuation and serious AEs were lower with Ibr than CIT. Future analyses examining the impact of factors such as age/comorbidity and race are warranted to further our understanding of RW outcomes in pts with CLL/SLL. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal