Treatment-related Hospitalizations Research Articles

Parental perception of treatment options for mucopolysaccharidosis: a survey to bridge the gap for personalized medicine.

Mucopolysaccharidosis (MPS) are a group of lysosomal storage diseases with substantial unmet medical needs-for both patients and caregivers. Approved therapies are limited, and the perception of investigative ones remains enigmatic. Using an innovative survey concept based on the discrete choice experiment method (DEC) with neuronopathic and non-neuronopathic patient scenarios, we aimed to evaluate how parents of children with MPS perceive different approved and innovative therapies. The questionnaire was distributed via patient organizations in Germany, Switzerland, and Austria. Most likely parents would choose an approach to repurposed treatments for their child (neuronopathic: 82%, 14/17 and non-neuronopathic: 94%, 16/17), followed by enzyme replacement therapy (ERT, both 88%, 15/17), hematopoietic stem cell therapy (HSCT, 70%, 12/17 and 76%, 13/17), and finally gene therapy (GT, 58%, 10/17 and 53%, 9/17). The general attitudes strongly influenced decision-making regarding treatment options. While over 80% of respondents who held a positive attitude toward ERT, HSCT, and ITTs indicated they would opt for these therapies in both neuronopathic and non-neuronopathic cases, only about half of the parents with a favorable general view of gene therapy (GT) expressed a positive perception of its likelihood as a treatment option. Furthermore, most parents found mild infections, injection site reactions (ISRs), hypertonia, and treatment-related hospitalizations acceptable and indicated patient organizations as their main source of information. This study provides an innovative survey method, thereby offering the rationale for a quantitative risk-benefit model and the importance of patient and caregiver-centered information dissemination, especially for innovative therapies.

Clinical Outcome Patterns of Use of Radium-223 in Patients with Metastatic Castration-Resistant Prostate Cancer.

Introduction: Radium-223 dichloride (radium-223) is a bone-targeting radioisotope therapy that aids in the survival of patients with metastatic castration-resistant prostate cancer (mCRPC) to bones. This study aimed to describe the clinical characteristics and outcomes of patients with mCRPC treated with radium-223 in a real-world setting. Methods: This was a retrospective study of patients with mCRPC treated with radium-223 between 2016 and 2020 at the London Health Sciences Centre in London, Canada. The baseline characteristics between the patients receiving 1-3 and 4-6 treatment cycles were compared using a two-sample t-test and Chi-square test. ANOVA was used to determine if there was a difference in each diagnostic variable per treatment cycle. Kaplan-Meier curves were generated to estimate progression-free survival (PFS) and overall survival in the patients treated with different numbers of cycles. Results: Fifty eligible patients were identified. The median age was 71 years (IQR: 66-76). Most patients (62%) received radium-223 beyond the third-line treatment. The mean number of radium-223 treatments was four. While 60% of the patients received 4-6 injections, 40% received 1-3 injections. Fifty-eight percent (58%) of the patients demonstrated a clinical benefit, with the remainder expressing either disease progression (28%) or stable disease (10%). The patients treated with 4-6 cycles had a delay to disease progression compared to those given 1-3 cycles of radium-223 (F5,35 = 10.52, p < 0.001). A higher alkaline phosphatase level prior to treatment was associated with a longer PFS (z33 = 2.362, p = 0.018). Treatment-related hospitalization for skeletal-related events was noted in 8% of the patients, and 14% required treatment discontinuation due to hematologic toxicity. Conclusions: This study confirms the safety of radium-223 in patients with mCRPC in a real-world setting. The radium-223 treatment was associated with a clinical benefit in the majority of the patients, particularly in those with higher pre-treatment serum alkaline phosphatase levels. Further studies to identify the predictive biomarkers are warranted to better guide the contemporary use of radium-223.

Abstract PO2-12-12: REaCT 5G: A randomized study comparing bone pain after 5 days of filgrastim or one day of pegfilgrastim for primary febrile neutropenia prophylaxis during neo-/adjuvant chemotherapy for early breast cancer

Abstract Background: Granulocyte colony stimulating factor (G-CSF) such as filgrastim (FIL) or pegfilgrastim (PEG) significantly reduces the risk of febrile neutropenia (FN) and treatment-related hospitalization in patients with early breast cancer receiving chemotherapy. However, patients receiving G-CSF can experience clinically significant bone pain. Previous studies examining post-GCSF bone pain were mostly based on physician pain assessment and compared mixed doses (30/60/100 μg/kg) of PEG vs. FIL (5μg/kg/day or 300 μg/day) given for 7 to 14 days. Based on a randomized non-inferiority study, 5 days of FIL is considered non-inferior to 10 days of FIL to prevent FN and hospitalizations and is frequently used in patients receiving chemotherapy for breast cancer. Patient-reported bone pain after 5 days of FIL vs. single dose of PEG has never been compared in a prospective randomized study and has important implications for patient and physician treatment preferences. Methods: In this multicenter, open-label trial, patients receiving neo-/adjuvant chemotherapy for early-stage breast cancer requiring primary FN prophylaxis with G-CSF were randomized 1:1 to either 5 days of FIL (300 μg or 480μg if ≥ 90 kg) or 1 day of PEG (6 mg) with each cycle of chemotherapy. The primary endpoint was bone pain using area under the curve (AUC) of the daily pain score from days 1-5 (AUC score 0 to 40) during cycle 1. We used linear regression adjusting for stratification factors [cancer center (2 centers) and chemotherapy regimen (taxane (TAX) or anthracycline (ANTH)-based during cycle 1] and prespecified baseline covariates: age, pain, and use of pain medications pre-chemotherapy. Supportive analysis of bone pain across cycles 1 to 4 was conducted using repeated linear regression. Key secondary endpoints included incidence of FN, hospitalizations, chemotherapy delay, dose-reduction or discontinuation, and chemotherapy-related deaths. Results: From June 2021 to March 2023, 233 patients were enrolled, with 217 patients (108 FIL/109 PEG) in the intention-to-treat analysis; 16 (7.4%) patients were excluded because of incomplete follow-up. Participants were mean age 55.6 years; almost exclusively female (99.1%), on chemotherapy regimen TAX 57% vs. ANTH 43%, had mean baseline pain score 1.12, and prevalence of pain medication use pre-chemotherapy was acetaminophen 14.7%, non-steroidal anti-inflammatory drugs (NSAIDs) 6.0% and opioids 3.2%. Characteristics were balanced between arms (Table 1). After repeated measures linear regression adjusted for age, chemotherapy regimen, baseline pain, and use of pain medications pre-chemotherapy, mean AUC for bone pain at cycle 1 was 10.94 for FIL and 10.12 for PEG (mean difference 0.82; 95% CI: -1.59, 3.23; p = 0.516). There was no significant difference between arms across treatment cycles (interaction p = 0.785; mean time-averaged difference 0.28; 95% CI: -1.75, 2.32). Across cycles 1 to 4, mean peak pain over 5 days post-GCSF was 3.27 vs. 3.41 (p=0.700); frequency of bone pain during first 8 days (pain score &amp;gt; 0) was 52.5% vs. 51.3%; p=0.358, and mean frequency of severe pain (pain score ≥ 5) was 17.5% vs. 15.2%; p=0.014 for FIL vs. PEG, respectively. The incidence of FN [4.6% vs. 0%, absolute difference 4.6% (95% CI: -0.3%, 9.5%; p=0.069)] and hospitalization [FN and non-FN related: 10.2% vs. 1.8%, absolute difference of 8.4% (95% CI: 1.2%, 15.5%; p=0.021)] was higher in the FIL group. There were no significant differences in chemotherapy delay (13% vs. 11%; p=0.815), dose reduction (14.8% vs. 14.7%; p=0.999), early discontinuation (8.3% vs. 5.5%; p=0.580), or chemotherapy-related death (0.9% vs. 0%; p=0.996) in the FIL vs. PEG groups, respectively. Conclusion: There was no difference in patient-reported bone pain after 5 days of FIL or PEG, even after controlling for important clinical factors. Importantly, the study observed higher rates of FN and hospitalizations in patients receiving FIL for 5 days only. Table 1 Baseline Characteristics Citation Format: Terry Ng, Yuxin Zhang, Carol Stober, Jennifer Shamess, Natalie Mills, Stuart Nicholls, Mohammed Ibrahim, Daniel Davoudpour, Christopher Armiento, Marie-France Savard, Moira Rushton, Arif Awan, Sandeep Sehdev, John Hilton, Xinni Song, Rakesh Goel, Fiona Macdonald, Kelly Daigle, Lisa Vandermeer, Monica Taljaard, Mark Clemons. REaCT 5G: A randomized study comparing bone pain after 5 days of filgrastim or one day of pegfilgrastim for primary febrile neutropenia prophylaxis during neo-/adjuvant chemotherapy for early breast cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO2-12-12.

Abstract PS14-02: Real-world analysis comparing Black and White patients with triple-negative breast cancer receiving therapy per KEYNOTE-522

Abstract Abstract Title: Real-world analysis comparing Black and White patients with triple-negative breast cancer receiving therapy per KEYNOTE-522 Background: KEYNOTE-522 was a randomized, double-blind, placebo-controlled phase 3 trial which resulted in the FDA approval of pembrolizumab with neoadjuvant chemotherapy for patients with newly diagnosed, high-risk, early-stage triple-negative breast cancer (TNBC). Despite the significant improvement in pathological complete response (pCR) and event-free survival rates across all patients, the landmark trial included only 4.5% Black patients. It is essential to assess outcomes in representative treatment populations. We assessed real-world toxicity and treatment outcomes across Black and White patients who received standard-of-care treatment per KEYNOTE-522. Methods: In this retrospective, multicenter study, we examined patients with early-stage TNBC who received planned treatment per KEYNOTE-522 as standard-of-care (SOC) therapy. 16 sites were included in the analysis. IRB approval was obtained from each participating site. Number and length of treatment delays, treatment-related toxicities (both chemotherapy and immune-related) of all grades, and pCR rate were collected from the electronic medical record of each participating site, and deidentified data were shared for central analysis. Results: Of the 577 patients who initiated treatment with chemotherapy and immunotherapy, 534 patients were included in this analysis with 105 patients who self-identified as Black (19.7%) and 429 who self-identified as White (80.3%). There were no statistically significant differences in clinical and pathological characteristics between the two groups. White women were more likely to have grade 3+ immune-related adverse events (irAEs) compared to Black women (33.8% vs 20.9%, P=0.011). There was no significant difference across Black and White patients with respect to grade 3+ chemotherapy-related adverse events. Out of the 444 patients who have completed surgery, no difference in pCR rate was observed between Black and White women (45/86 52.3% vs 200/358 55.9%) (p = 0.6). The authors also saw no difference in the rates of hospitalizations between Black and White women (39% vs 36% p = 0.5), and rates of acute care utilization (38% vs 38% p = 0.9). Conclusions: We report safety and efficacy across Black and White women in a real-world analysis of patients who received treatment per KEYNOTE-522. Notably, White patients had a significantly higher frequency of grade 3+ irAEs, although the reason for this finding is unclear based on this analysis. Black patients had similar pCR rates and rates of treatment-related hospitalizations compared to White patients. Assessment of outcomes and toxicity by race in clinical trials and real-world analyses are critical in drug development. Citation Format: Mara Hofherr, Andrew Davis, Spenser January, Emily Owen, Farah Raheem, Lida A. Mina, Suganya Arunachalam Karikalan, Lauren Lyons, Meredith Watson Rose, Katherine Madden, Jerline Hsin, Aimee Keegan, Wai Yu, Shawna Kraft, Allison Schepers, Emily Armgardt, Douglas Mazewski, Alison Svoboda, Kayla Harwood, Jodi Taraba, Yonatan Resnick, Shelly Hummert, Lisa Grate, Sidney Keisner, Jacob Hobbs, Todd Davis, Kristin Bastian, Dawn Minikel, Wiliam Adler, Traci White, Avneek Singh Sandu, Fouad Boulbol, Kelsey Finch, Katherine Clifton. Real-world analysis comparing Black and White patients with triple-negative breast cancer receiving therapy per KEYNOTE-522 [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PS14-02.

Proton Beam Therapy (PBT) Versus Intensity-Modulated Radiotherapy (IMRT) for Locally Advanced Non-Small Cell Lung Cancer (LA-NSCLC) in the Era of Immune Checkpoint Inhibitor (ICI) Consolidation: A Retrospective Cohort Study

Patients (pts) with LA-NSCLC treated with concurrent chemoradiation (cCRT) and ICI consolidation are at high risk for treatment-related toxicities and subsequent hospitalization. We hypothesized that PBT is associated with a reduction in acute unplanned hospitalizations as compared to IMRT in the era of ICI consolidation. This single institution, multi-site retrospective study included consecutive pts with LA-NSCLC treated with definitive cCRT with either PBT or IMRT from October 2017 to December 2021. Pts were evaluated for consolidative ICI. Primary endpoint was unplanned treatment-related hospitalization within 90 days of first radiation (RT) treatment. Secondary endpoints included grade 3+ pneumonitis, grade 3+ esophagitis, PFS and OS. Logistic regression was used to assess associations with 90-day hospitalization. Competing risk regression was used for grade 3+ pneumonitis and esophagitis, and Cox regression for PFS and OS. A total of 316 pts were included: 117 (37%) received PBT and 199 (63%) IMRT. Median age was 68.5 yrs; median RT dose 66.6 Gy (IQR 65.9-70.0). PBT group was older (median 71.1 vs 67.2 yrs, p<0.005) and had a higher Charlson comorbidity index (CCI) (median 4 vs 3, p = 0.02). There was no significant difference in ECOG, smoking pack-years, T stage, N stage, target volume size, or receipt of ICI consolidation (66.7% vs 68.3%, p = 0.76). PBT group had lower mean heart dose (5.9 vs 10.8 Gy, p<0.001), LAD V15 (0 vs 6 %, p = 0.001), mean lung dose (14.7 vs 15.7 Gy, p <0.008) and effective dose to immune circulating cells (median 3.7 vs 4.9 Gy, p<0.001) but not mean esophagus dose. PBT was associated with fewer unplanned 90-day hospitalizations (23.9% vs 34.7%); which persisted on multivariable analysis (OR 0.52, 95% CI 0.30-0.90, p = 0.02) after adjusting for CCI, smoking pack-years, T4 tumors and target volume. Reasons for hospitalization in PBT and IMRT groups included progression (1.7% vs 1.5%), definite/probable toxicity from cCRT (11.1% vs 18.6%), possible toxicity from cCRT (7.7% vs 12.6%) or unrelated to cCRT (3.4% vs 2.0%). There was no significant difference between PBT or IMRT groups in G3+ pneumonitis (1-year 6.0% vs 9.1%, p = 0.49), G3+ esophagitis (1-year 6.0% vs 6.5%, p = 0.71), PFS (median 14.4 vs 15.1 months, p = 0.69), or OS (median 34.2 vs 29.4 months, p = 0.41). Among pts with LA-NSCLC treated with cCRT in the era of ICI consolidation, PBT was associated with fewer acute unplanned hospitalizations compared to IMRT. There was no difference in G3+ pneumonitis, G3+ esophagitis, PFS or OS.

Real-world outcomes in advanced melanoma patients treated with first-line nivolumab plus ipilimumab.

e21552 Background: Nivolumab plus ipilimumab (NIVO+IPI), a first-in-class combination immunotherapy, has dramatically changed the treatment paradigm for melanoma in recent years. The aim of this study was to analyze treatment patterns, treatment response, survival, safety, and healthcare resource utilization with this first-line combination therapy in patients (pts) with advanced melanoma under real-world conditions. Methods: This retrospective analysis included pts with stage 3 unresectable and stage 4 melanoma treated 01/2021-06/2022 with NIVO+IPI at 6 centers in Poland according to uniform criteria. Pts received up to 4 cycles of IPI 3 mg/kg + NIVO 1 mg/kg Q3W followed by maintenance NIVO (240 mg Q2W or 480 mg Q4W) until disease progression, unacceptable toxicity or at the request of the patient or physician. Kaplan-Meier estimator and Log-rank test were used in survival analysis. Results: A total of 291 adults were identified. The median age was 53 years, 42.5% of pts were female, 47% were BRAF-mutated, and 24% of pts received prior adjuvant treatment. At baseline, 19.5% of pts had stage III disease, 14.1% stage M1a, 13.7% stage M1b, 30.1% stage M1c and 23% had M1d disease. Median follow-up time was 11.9 months. The median number of cycles of NIVO+IPI administered was 3, with 47.9% of pts completing 4 cycles. Maintenance NIVO was continued in 52.7% pts who discontinued the combination therapy due to toxicity. Median progression-free survival (mPFS) was 9.8 months (95% CI 6.9–13.4). The longest mPFS was observed in pts with stage M1a (15 months; 95%Cl 3.1–NA) and the shortest in stage M1d pts (5 months; 95%CI 2.8–NA). We observed a statistically significant longer mPFS in pts who continued NIVO monotherapy after discontinuation of combination therapy due to toxicity (13 months, 95% Cl 10.4–NA) compared to those who discontinued immunotherapy (7.1 months, 95% Cl 3.4 –12; p &lt; 0.0001). Median overall survival (OS) was not achieved, with an OS rate of 70% at 12 months (95%Cl 64–76). The objective response rate (ORR) was 39%, with 7.8% of pts achieving a complete response. For pts who received prior adjuvant therapy, the ORR was 24.2%. Treatment-related adverse events (TRAEs) of any grade were observed in 97% of pts and grade 3/4 TRAEs occurred in 29.6% of pts. The most common TRAEs were liver toxicity, colitis, hyperthyroidism, hypothyroidism, and hypopituitarism; the treatment-related hospitalization rate was 23.8% and the median length of hospital stay was 9 days. Conclusions: This real-world study confirms the high efficacy of NIVO+IPI in real-world settings with grade 3/4 toxicity lower than observed in clinical trials. Maintenance of NIVO despite early toxicity during combination treatment appears to have a beneficial effect on patient survival. Therefore, it is extremely important to carefully monitor pts for toxicity, as early intervention helps to avoid severe toxicity and premature discontinuation of treatment.

Prognostic role of geriatric assessment (GA) in patients with metastatic prostate cancer (MPCaP) attended in medical oncology.

90 Background: The Geriatric Assessment (GA) represents the future of the geriatric oncology to reduce toxicities and treatment-related hospitalization in the elderly. It has demonstrated results in predicting chemotherapy feasibility and response to docetaxel in patients with metastatic castration-resistant prostate cancer (MCRPca) (Della pepa). GA has also been explored in patients suitable to oral treatment (ref). In order to understand the prognostic capabilities of GA, we developed this analysis. Methods: All patients with MPCa sent to evaluation for Medical Oncology from January 2020 to August 2022 were analysed. GA was applied to those with 70 years or more. A geriatrician and/or an oncologist performed the evaluation. Informed consent was signed for patients. Ethical committee approved the protocol. Results: 85 patients were sent to Medical Oncology, 40 young (40%), 51 elderly (50%). Median age for young patients was 62 (46-68) and 79 for elderly (70-91). A comparison between populations is shown. This was an observational prospective study involving 51 patients who were 70 years of age or older. We performed GA including five domains and divided our patients into “fit”, “lower frailty,” and “high frailty” using Rockwood frailty scale. The relation between GC group and overall survival was explored. After GA, 26 were fit (51%), 16 had lower frailty (30%) and 10 had high frailty (19%). We found a statistically significant relationship between GA group and overall survival. Fit patients had overall survival of 27,1 months (22,8-31,5) versus 15,1 months (9,7-19,4) for low frailty and 5,6 months (3,2-7,9) for high frailty (p;0,000). Conclusions: Although our analysis has a selection bias as we only explored elderly patients sent to Medical Oncology, we found that a GA may help clinicians to recognize frail patients, and hence to reduce toxicities and early treatment discontinuation. We demonstrate its capability to be incorporated into routine clinical practice. [Table: see text]

Real-world comparison of outcomes in the first line treatment of metastatic melanoma according to BRAF mutation status: Nivolumab and ipilimumab therapy vs. nivolumab monotherapy.

e21519 Background: In metastatic melanoma (MM) patients, nivolumab can be used as monotherapy or in combinations with ipilimumab. The combination therapy has been shown in a randomized clinical trial to provide survival benefit in BRAF mutant patients with an increased toxicity. Using real-world data, we evaluated the impact on overall survival and post-treatment hospitalizations of 1L nivo alone vs nivo+ipi. Methods: We performed a retrospective cohort study of 1L treatment of patients with MM between 1/2016 and 12/2020, utilizing administrative claims data from the Anthem Cancer Care Quality Program. Real-world overall survival (OS) was defined as time from diagnosis to death. A Cox model with inverse probability of treatment weighting (IPTW) was used to adjust for demographic and clinical features. Adjusted hazard ratios (aHR) were estimated using weighted Cox proportional hazards models. Results: Our cohort included 708 1L MM patients, of them 466 (66%) treated with nivo+ipi. There was no difference in BRAF status between the treatment groups. Patients treated with nivo+ipi were younger and had more evidence of brain and lung metastasis. Following adjustment, nivo treated had significant longer OS compared to the nivo+ipi treated (aHR: 1.73 (1.25-2.35), p = 8e-4). This difference mostly stems from increased mortality of the combo treated in the first 6 months. At 24-months, 58% of the combination therapy treated patients were alive compared to 74% in the monotherapy group (p = 0.0006). Survival benefit was only observed in BRAF WT patients. In V600E patients no survival difference was observed (aHR: 0.8 (0.4-1.6), p = 0.5). Patients treated with the combination therapy had 5-fold more hospitalizations during the first 90 days after the treatment start (46% vs 10%, p = 3e-22). Conclusions: Our retrospective cohort study demonstrated improved survival for the monotherapy in BRAF WT patients. Combination therapy was associated with significantly more treatment-related hospitalizations and deaths, mainly in the first 6 months. The increased early morbidity of the combo should be considered in treatment decision.[Table: see text]

Abstract OT2-21-01: A randomized, multicenter pragmatic trial comparing bone pain from a single dose of pegfilgrastim to 5 doses of daily filgrastim in breast cancer patients receiving neoadjuvant/adjuvant chemotherapy (REaCT-5G)

Abstract Background: Current guidelines recommend the use of granulocyte colony-stimulating factors (G-CSF) as primary prophylaxis to prevent febrile neutropenia (FN) associated with commonly used breast cancer chemotherapy regimens. Filgrastim (FIL) is a short-acting G-CSF injection that requires daily subcutaneous injection starting 24-72 hours after chemotherapy for 5 to 10 days. Pegfilgrastim (PEG) is a long-acting, pegylated formulation that requires a single injection 24-72 hours after chemotherapy. G-CSF causes bone pain in approximately 70% of patients, which can be severe in over 25% of cases. While registration trials for PEG showed bone pain from PEG was comparable to FIL when given for a median duration of 11 days, many oncologists are now only prescribing FIL for 5 days based on a multicenter RCT showing that 5 days of FIL is non-inferior to 7 or 10 days of FIL in terms of FN and treatment-related hospitalizations. Furthermore, the cost of 5 days of FIL ($CA 721.55 for 300 mcg dose) is half of the price of a single dose of PEG ($CA 1424.63). Therefore, if 5 days of FIL leads to significantly less bone pain, this may improve health-related quality of life (HR-QoL) for patients, improve adherence to G-CSF, and improve cost-effectiveness. Methods: Patients receiving neo-/adjuvant chemotherapy for early stage breast cancer requiring primary FN prophylaxis with G-CSF will be approached for this pragmatic, multicenter, open-label superiority RCT. Using the Rethinking Clinical Trials (REaCT) methodology that incorporates an integrated oral consent model, eligible and consented patients will be randomized to either 5 days of FIL or one day of PEG with each cycle of chemotherapy. The primary endpoint is bone pain during the first 5 days after G-CSF injection using area under the curve (AUC) of the daily pain score from days 1-5 (AUC score 0 to 40) of the Bone Pain Diary. Secondary endpoints include incidence of FN and treatment-related hospitalizations, incidence of chemotherapy delay, dose-reduction, or discontinuation, incidence of chemotherapy-related mortality, rate of G-CSF compliance, healthcare resource utilization, HR-QoL, and cost-effectiveness. Participants will also complete a Treatment Preference Questionnaire (TPQ) exploring the relative importance of different factors in deciding between PEG vs. 5 days of FIL both before randomization and at the end of the study. To achieve 80% power in an ANCOVA analysis and assuming 5% are loss to follow-up, the planned sample size is 232 patients (116 per arm). The randomization (1:1 ratio) will be stratified by treatment center (4 centers) and chemotherapy regimen (taxane-based vs. anthracycline-based in the first 4 cycles). Results: The study opened for enrollment on June 9, 2021. As of July 6, 2021, the study has opened at one site, and 13 patients have been randomized.Conclusion: This will be the first RCT using a patient-reported Bone Pain Diary that was co-developed by patient partners to measure bone pain between 5 days of FIL vs. PEG. In collaboration with patient partners, the study incorporates a tool (TPQ) that explores factors that may be important in deciding between PEG and FIL, with the aim of translating the findings of this study into real world clinical practice. Citation Format: Terry L. Ng, Monica Taljaard, Marie-France Savard, Carol Stober, Stuart Nicholls, Lisa Vandermeer, Kednapa Thavorn, Claudia Hampel, Jennifer Shamess, Natalie Mills, John F. Hilton, Mark Clemons. A randomized, multicenter pragmatic trial comparing bone pain from a single dose of pegfilgrastim to 5 doses of daily filgrastim in breast cancer patients receiving neoadjuvant/adjuvant chemotherapy (REaCT-5G) [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr OT2-21-01.

Health-system specialty pharmacy impact on oral chemotherapy outcomes.

240 Background: Oral chemotherapy usage has grown significantly over the years as it provides a more convenient and less invasive administrative option for patients.In 2019, 89% of large hospitals owned and operated their own Health System Specialty Pharmacies (HSSP)1.Pharmacist-led medication therapy management services are crucial to provide patient education, monitoring of medication adherence and adverse effect management. With the current vertical integration of health plans and pharmacy benefit managers (PBMs) increasing their dominance over specialty dispensing channels, HSSP are often excluded from specialty networks. The objective of this study is to compare outcomes of oncology patients filling their oral chemotherapy at Cedars Sinai Medical Center (CSMC) Specialty Pharmacy versus those who are filling their medications at outside specialty pharmacies (OSP). Methods: Electronic health records were used to conduct a retrospective chart review of patients started on oral chemotherapy at CSMC between January 2019 to January 2021. Primary endpoints included time to treatment (TTT) and proportion of days covered (PDC). Secondary endpoints included drug-related problems (DRPs) and treatment-related ED visits and hospitalizations. DRPs were categorized by severity and type of intervention. Results: There were 100 patients included in the study: CSMC group (n = 50) and OSP group (n = 50). Patients in the CMSC group had significantly shorter TTT compared to OSP group (4 days vs. 9.5 days, respectively [P &lt; 0.0026]), as well as a higher PDC (99.5% vs 91%, respectively [P &lt; 0.0005]). Pharmacists identified and resolved 31 DRPs in CSMC arm with 19 DRPs categorized as serious and 1 DRP categorized as life-threatening. For the OSP group, 23 preventable DRPs were identified with 12 DRPs categorized as serious and 1 DRP categorized as life-threatening. There were no treatment-related ED visits or hospitalizations in either group. Conclusions: Patients filling their oral chemotherapy at CSMC Specialty Pharmacy had significantly quicker TTT and higher adherence rates as measured by PDC. Numerous DRPs were identified for OSP patients; potential pharmacist-interventions could have led to optimized and safer medication therapy if filled at a HSSP. Continued research comparing treatment outcomes and interventions made between HSSP and OSP can create a strong argument for health plans and PBMs to consider inclusion of HSSPs into their specialty networks.

Machine learning-based approach to the risk assessment of potentially preventable outpatient cancer treatment-related emergency care and hospitalizations.

333 Background: Patients undergoing outpatient infusion chemotherapy for cancer are at risk for potentially preventable, unplanned acute care in the form of emergency department (ED) visits and hospital admissions. This can impact outcomes, patient decisions, and costs to the patient and healthcare system. To address this need, the Centers for Medicare &amp; Medicaid Services developed the Chemotherapy Measure (OP-35). Recent randomized controlled data indicate that electronic health record (EHR)-based machine learning (ML) approaches accurately direct supportive care to reduce acute care during radiotherapy. As this may extend to systemic therapy, this study aims to develop and evaluate ML approaches to predict the risk of OP-35 qualifying, potentially preventable acute care within 30 days of infusional systemic therapy. Methods: This study included data from UCSF cancer patients receiving infusional chemotherapy from July 1, 2017, to February 11, 2021, (total 7,068 patients over 84,174 treatments). The data incorporated into the ML included 430 EHR-derived variables, including cancer diagnosis, therapeutic agents, laboratory values, vital signs, medications, and encounter history. Three ML approaches were trained to predict an OP-35 acute care risk following a systemic therapy infusion with least absolute shrinkage selection operator (LASSO), random forest, and gradient boosted trees (GBT; XGBoost) approaches. The models were trained on a subset (75% of patients; before October 12, 2019) of the dataset and validated on a mutually exclusive subset (25% patients; after October 12, 2019) based on the receiver operating characteristic (ROC) curves and calibration plots. Results: There were 1,651 total acute care visits (244 ED visits and 1,407 ED visits converted into hospitalization); 1,310 infusions included a qualifying acute care visit (200 with ED visits only, 0 direct hospital admissions, and 1,110 with both ED visit and hospitalization). Each ML approach demonstrated good performance in the internal validation cohort, with GBT (AUC 0.805) outpacing the random forest (0.750) and LASSO logistic regression (0.755) approaches. Visualization of calibration plots verified concordance between predicted and observed rates of acute care. All three models shared patient age and days elapsed since last treatment as important contributors. Conclusions: EHR-based ML approaches demonstrate high predictive ability for OP-35 qualifying acute care rates on a per-infusion basis, identifying 30-day potentially preventable acute care risk for patients undergoing chemotherapy. Prospective validation of these models is ongoing. Early prediction can facilitate interventional strategies which may reduce acute care, improve health outcomes, and reduce costs.

Real-world outcomes in patients with metastatic renal cell carcinoma treated with first-line nivolumab plus ipilimumab.

305 Background: Nivolumab plus ipilimumab (NIVO+IPI), a first-in-class combination immunotherapy, was approved by the US Food and Drug Administration in April 2018 for the treatment of intermediate- or poor-risk advanced renal cell carcinoma (RCC), and the treatment paradigm has changed dramatically over the past few years. This real-world study examined treatment patterns and sequences, treatment response, safety, and survival outcomes with this novel first-line (1L) combination therapy among patients diagnosed with metastatic RCC (mRCC) in a community oncology practice setting. Methods: A retrospective analysis of the US Oncology Network’s iKnowMed medical data examined adult patients with an International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) prognosis of intermediate- or poor-risk clear cell mRCC who received 1L NIVO+IPI between April 1, 2018, and March 31, 2020. Baseline demographic and clinical characteristics, treatment patterns, and treatment sequence were examined descriptively. Overall survival (OS), progression-free survival (PFS), objective response rate (ORR), duration of response (DoR), time to treatment discontinuation (TTD), and time to treatment response (TTR) were analyzed using the Kaplan–Meier method. Treatment-related adverse events (TRAEs) and healthcare resource utilization were also analyzed. Results: A total of 193 adults with stage IV mRCC treated with 1L NIVO+IPI were identified. Median age (range) was 63 (30.0–89.0) years, 73.1% were male, 69.4% were white, 56.7% were IMDC intermediate risk, and 60.6% had a documented Eastern Cooperative Oncology Group performance status of 0 or 1. Median follow-up time (range) was 9.7 (0.1–24.7) months. Median PFS (95% CI) was 17.1 (12.6–21.2) months, and the 1-year landmark PFS rate was 58.3% (50.4–65.4). At 12 months, the OS rate (95% CI) was 75.4% (67.8–81.4). The ORR (95% CI) was 43.2% (34.6–52.1) among patients with a response assessment; the median TTR (range) was 2.8 (0.3–4.1) months and median DoR was not reached. Median TTD (95% CI) was 5.8 (4.5–7.5) months. Among the 63 (31.3%) patients who received second-line therapy, 50.8% received cabozantinib and 12.7% received pazopanib. TRAEs were reported in 47.2% of patients—the most frequently reported were fatigue (13.5%), rash (10.4%), diarrhea (6.7%), nausea (6.2%), colitis (3.6%), and pruritus (3.6%). The treatment-related hospitalization rate was 5.5% and the emergency department visit rate was 3.1%. Conclusions: This real-world study supports the clinical efficacy of 1L NIVO+IPI for patients with mRCC. Our findings also suggest that the NIVO+IPI combination was generally well tolerated in the real-world setting, with low rates of adverse events and healthcare resource utilization.

The use of pembrolizumab and lenvatinib combination therapy in endometrial cancer: an examination of toxicity and treatment efficacy in clinical practice

<h3>Objectives:</h3> Pembrolizumab/lenvatinib demonstrated impressive response rates in advanced/recurrent endometrial cancer (EC) in a recent phase II clinical trial, leading to its accelerated FDA approval. However, tolerability of the recommended 20 mg starting dose of lenvatinib may pose clinical challenges. To comprehend how this regimen translates into daily clinical practice, we evaluated our preliminary data regarding toxicity and efficacy of pembrolizumab/lenvatinib in the treatment of advanced/recurrent EC at the University of Texas MD Anderson Cancer Center. <h3>Methods:</h3> In this single-institution, retrospective cohort study, we evaluated recurrent/advanced EC patients who received ≥1 cycle of pembrolizumab/lenvatinib treatment. Toxicity was evaluated through rates of hospitalization and treatment interruptions or discontinuations, as well as number of dose reductions. Clinical efficacy was evaluated by best radiologic response to treatment. Clinical benefit was defined as having stable disease or partial/complete response. <h3>Results:</h3> From October 2019 to July 2020, 83 EC patients were identified but 16 were excluded for unconfirmed administration of pembrolizumab/lenvatinib or lack of toxicity or response data. Thus, 67 EC patients were included in the analysis with a median follow-up of 5 months (range 1 - 11). The median age and number of prior lines of therapy were 67 (range 31–77) and 2 (range 1–9), respectively. The majority had an ECOG performance status of 0 to 1 (91%). The predominant histologic subtype was endometrioid and serous (n=19 each) followed by carcinosarcoma (n=13), mixed (n=8), clear cell (n=4), and other (n=4). The most common starting dose of lenvatinib was 14 mg (n=43; 64.2%), followed by 20 mg (n=15; 22.4%). Treatment-related hospitalizations occurred in 26.9% of patients but did not differ between lenvatinib dosage groups (p=0.37). Compared to those with a lower starting dosage level, patients started on 20 mg doses had significantly higher treatment discontinuations (100% vs 69.2%, p=0.01) and numbers of lenvatinib dose reductions (1.0 vs 0.38, p=0.004), with a trend of higher treatment interruptions (93.3% vs 73.1%, p=0.09). Among the 56 patients with evaluable radiologic response, there were 21 (37.5%) patients with either a partial (n=18) or complete response (n=3), while 18 patients (32.1%) had stable disease. Of the patients with complete response, all patients had a starting lenvatinib dose of 14 mg. Based on a starting lenvatinib dose of 20 mg vs < 20 mg, there were no differences in response to therapy (23.1% vs 41.9%; p=0.56; respectively) or clinical benefit rates (53.8% vs 74.4%, p=0.18; respectively). There were no differences in response rates among histologic subtypes (p=0.76). Patients with carcinosarcoma histology had a response and clinical benefit rate of 25% (3 of 12) and 58.3% (7 of 12), respectively. <h3>Conclusions:</h3> In treatment of recurrent/advanced EC, lower starting dosage of lenvatinib was associated with fewer treatment interruptions/discontinuations and dose de-escalations compared to the FDA recommended 20 mg dosage level while maintaining equivalent response and clinical benefit rates. Furthermore, patients with carcinosarcoma histology also appeared to benefit from pembrolizumab/lenvatinib. While larger studies are needed to validate these safety and efficacy findings, our preliminary data supports starting a lower dosage of lenvatinib in clinical practice.

Increased risk of immune-related hepatitis among adolescent and young adults (AYAs) with melanoma during immunotherapy with checkpoint inhibitors (ICIs).

9584 Background: Melanoma is the second most common malignancy affecting AYA patients after lymphoma. Nevertheless, AYA melanoma does constitute a minority of all melanoma cases. Additionally, the AYA population is not well represented in prospective clinical trials, including immunotherapy trials. While previous research has demonstrated the efficacy of ICIs across age groups, it remains unclear if toxicity profiles will be similar. In the general population, age-related changes in the immune milieu result in differential incidences of autoimmune diseases by age. This study aims to compare the toxicity profile between a cohort of AYA melanoma versus elderly melanoma patients receiving ICI therapy. Methods: In this single NCCN institutional study, electronic medical records of melanoma patients treated with ICIs between 01/2007-01/2019 were reviewed. Subjects receiving concurrent investigational agents or chemotherapy were excluded. The AYA cohort included those aged 15-40 years. The elderly cohort included those aged ≥65 years. Adverse events were coded according to CTC-AE version 5.0. Multivariable logistic regression analyses were performed. Results: Analyses included 184 treatment courses. In the AYA cohort (N = 57), median age at ICI initiation was 28.8 years (range: 17.9-39.3). In the Elderly cohort (N = 127), median age at ICI initiation was 72.3 years. More AYA patients (28.1% AYA vs. 7.9% Elderly) received ICI combination regimens. The most common adverse events amongst both cohorts were transaminitis (23.4%), rashes (49.5%), and diarrhea/colitis (20%). Incidences of pneumonitis, colitis, hypothyroidism, and hypophysitis did not differ significantly between cohorts. However, the AYA cohort experienced a higher incidence of transaminitis (38.6% AYA vs. 16.5% Elderly, p =0.001 ) and increased occurrence of treatment related hospitalization (26.3% AYA vs. 7.1% Elderly, p &lt;0.001 ). Moreover, a higher proportion of severe grade ≥3 transaminitis occurred in the AYA group (27.3% AYA vs. 9.5% Elderly, p =0.004). While occurrence of transaminitis was significantly associated with combination ICIs, the association between AYA status and transaminitis remained significant after adjusting for ICI regimen (OR 2.75, 95% CI: 1.3-5.8). There was a trend toward shorter time to transaminitis onset among the AYA than Elderly cohort (median 53.0 vs. 74.5 days [non-parametric p= 0.28]). To date, median survival has not been reached in both groups ( p= 0.09). Conclusions: In this large cohort of AYA melanoma patients treated with ICI, we found a significantly higher incidence of immune-related transaminitis than in the Elderly cohort. Other immune-related AEs were comparable between cohorts. This finding was independent of ICI regimen. Further investigation will be needed to understand these differences between the AYA and Elderly cohorts.

Factors associated with hospitalization in patients (pts) with locally advanced squamous cell carcinoma of the head and neck (LA-HNSCC) treated with definitive chemoradiation (CRT).

e18035 Background: Definitive CRT is the standard of care for LA-HNSCC and associated with mucosal toxicity and treatment-related morbidity. Nutritional support via gastrostomy tube (G-tube) during CRT may reduce treatment-related complications. This study aims to identify factors associated with hospitalization in pts with LA-HNSCC treated with CRT. Methods: We conducted a medical record review of pts with LA-HNSCC treated with CRT between January 2010 and December 2019 at the VA San Diego Medical Center. Demographic and clinical factors were compared for pts based on hospitalization and G-tube placement. Logistic regression was used to identify associations with hospitalization and treatment interruptions. Results: Data on 100 pts (98% male) were analyzed. 21 pts were hospitalized, and 17 pts had radiation treatment (RT) interrupted. 72 pts had prophylactic G-tube (p-G-tube) placement, and 11 pts had reactive G-tube (r-G-tube) placement. Hospitalized and non-hospitalized pts did not differ by ethnicity, alcohol use status, or chemotherapy type. Hospitalized vs non-hospitalized pts were older (mean 67.6 vs 63.8, P = 0.043), more likely to lose more weight during CRT (-14.90% vs -10.60%, P = 0.009), less likely to complete CRT (71.4% vs 92.4%, P = 0.009), and more likely to have chemotherapy (42.9% vs 3.8%, P &lt; 0.001) and RT interruptions (71.4% vs 2.5%, P &lt; 0.001). Logistic regression used to predict hospitalization and RT interruption were significant (X2= 35.24, P = 0.002 and X2= 31.97, P = 0.007, respectively). The effect testing p-G-tube vs r-G-tube placement was the only factor significantly associated with lower likelihood of hospitalization during CRT (Wald = 4.61, P = 0.032) and RT interruption (Wald = 6.02, P = 0.014). Pts with r-G-tube placement lost more weight during CRT (-16.79% vs -10.82% with p-G-tube, -10.97% with no G-tube, P = 0.022), had higher hospitalization rates during CRT (72.7% vs 18.1% with p-G-tube, 0% with no G-tube, P &lt; 0.001), had increased likelihood of RT interruption (63.6% vs 13.9% with p-G-tube, 0% with no G-tube, P &lt; 0.001), and were more likely to receive weekly cisplatin (45.5% vs 9.7% with p-G-tube, 41.2% with no G-tube, P = 0.018). Prophylactic G-tube placement was associated with current smoking status (43.1% vs 9.1% with r-G-tube, 41.2% with no G-tube, P = 0.009), bolus cisplatin (52.8% vs 36.4% with r-G-tube, 35.3% with no G-tube, P = 0.018), and cetuximab (27.8% vs 9.1% with r-G-tube, 11.8% with no G-tube, P = 0.018). Conclusions: Prophylactic G-tube placement should be considered for pts with LA-HNSCC treated with CRT regardless of smoking history and chemotherapy choice to decrease treatment-related hospitalizations and RT interruptions. This may be more important for indigent pts since prior research has shown treatment interruptions occur at higher rates in this at-risk population.

A multi-centre study comparing granulocyte-colony stimulating factors to antibiotics for primary prophylaxis of docetaxel-cyclophosphamide induced febrile neutropenia

BackgroundPrimary febrile neutropenia (FN) prophylaxis with ciprofloxacin or granulocyte-colony stimulating factors (G-CSF) is recommended with docetaxel-cyclophosphamide (TC) chemotherapy for early-stage breast cancer (EBC). A pragmatic randomised trial compared the superiority of G-CSF to ciprofloxacin and a cost-utility analysis were conducted. MethodsEBC patients receiving TC chemotherapy were randomised to ciprofloxacin or G-CSF. The primary outcome was a composite of FN and non-FN treatment-related hospitalisation. Secondary outcomes included; rates of FN, non-FN treatment-related hospitalisation, chemotherapy dose reductions/delays/discontinuations. Primary analysis was performed with the intention to treat population. Cost-utility analyses were conducted from the Canadian public payer perspective. Results458 eligible patients were randomised: 228 to ciprofloxacin and 230 to G-CSF. For the primary endpoint there was non-statistically significant difference (Risk difference = −6.7%, 95%CI = −13.5%–0.1%, p = 0.061) between ciprofloxacin patients (46,20.2%) and G-CSF (31,13.5%). Patients receiving ciprofloxacin were more likely to experience FN (36/228, 15.8% vs 13/230, 5.7%) than patients receiving G-CSF (p < 0.001). Non-FN treatment-related hospitalisation occurred in 40/228 (17.5%) of ciprofloxacin patients vs 28/230 (12.2%) of G-CSF patients (p = 0.12). There were no differences in other secondary outcomes. G-CSF was associated with an incremental cost-effectiveness ratio of C$1,760,796 per one quality-adjusted life year gained. ConclusionThe primary endpoint of superiority of G-CSF over ciprofloxacin was not demonstrated. While there were reduced FN rates with G-CSF, there were no differences in chemotherapy dose delays/reductions or discontinuations. With the commonly used willingness to pay value of C$50,000/QALY, G-CSF use was not cost-effective compared to ciprofloxacin and deserves scrutiny from the payer perspective.

Palliative Thoracic Radiotherapy for Non-Small Cell Lung Cancer in Outpatients: Reasons for Unplanned Hospitalization and Its Impact on Survival.

BackgroundThe aims of the study were to examine the rates of and reasons for unplanned hospitalization after start of palliative radiotherapy or chemoradiation (CRT), and to study whether unplanned hospitalization deteriorates patients’ prognosis. In addition, risk factors were identified.MethodsA retrospective review of 136 patients treated with palliative radiotherapy or CRT was performed. Inclusion criteria were prescribed total dose at least 30 Gy and outpatient at the start of treatment. Uni- and multivariate analyses were employed.ResultsFifty-eight patients (43%) were hospitalized within 3 months from start of radiotherapy or CRT. Their median overall survival was 6.7 months as compared to 11.1 months in non-hospitalized patients (P = 0.09). The median length of hospitalization was 8 days (range 1 - 61). In patients with possibly treatment-related hospitalization (n = 32), median survival was 5.0 months, significantly shorter than the 11.1 months observed in the remaining patients (P = 0.006). In multivariate analysis, only one variable was significantly associated with higher risk of unplanned hospitalization: previous hospitalization in the last 4 weeks before commencing radiotherapy or CRT.ConclusionsUnplanned hospitalization occurred frequently in a standard care setting without early involvement of a dedicated palliative team. Patients with preceding hospitalization might represent a group that is particularly vulnerable, thus qualifying for a targeted intervention aiming at continued outpatient care.

Using machine learning to identify older adults at high risk for hospitalization and mortality via the Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE).

169 Background: PRO-CTCAE captures symptomatic adverse events (e.g. pain, fatigue) and may indicate poor treatment tolerability in older patients (pts) with advanced cancer. Using unsupervised machine learning which can detect unknown patterns in data, we aimed to evaluate if clusters identified based on PRO-CTCAE severity were associated with hospitalization and survival. Methods: We included pts randomized to the control arm of GAP 70+ (URCC 13059; PI: Mohile), which enrolled pts aged ≥70, with incurable solid tumors or lymphoma, and ≥1 geriatric assessment (GA) domain impairment starting a new treatment regimen. Measures included 24 PRO-CTCAE items (v1.0) with severity attributes (item 0-4; total score 0-96, higher score = greater severity). The unsupervised algorithm (K-means with Euclidean Distance) clustered pts at baseline based on similarities of severities of the 24 items. We examined if the clusters were associated with treatment-related hospitalization within 3 months and lower survival at 6 months using Logistic and Cox regressions. Results: Of the 369 control pts, 366 completed GA and PRO-CTCAE at baseline (mean age 77.2, 94.3% white, 30.9% with GI and 31.4% with lung cancer; mean number of impaired GA 4.4). By PRO-CTCAE, the most prevalent symptoms were fatigue (82.7%), pain (60.9%), and decreased appetite (58.7%). Greater GA impairment was associated with 20 PRO-CTCAE items (fatigue, pain, and decreased appetite having the strongest associations; all Pearson's r &gt; 0.33). Three clusters were identified: Low Severity (51.4%); Moderate Severity (34.4%), and High Severity (14.2%). Mean total severity score was 6.9 (low), 16.9 (moderate), and 28.7 (high), respectively (p &lt; 0.01). No difference in demographics was found among clusters. Percent of pts hospitalized were 21.3% (low), 36.5% (moderate), and 38.5% (high) (p &lt; 0.01); survival rates were 81.9% (low), 71.4% (moderate), and 55.3% (high) (p &lt; 0.01). Controlling for cancer type and GA, compared to pts in Low Severity cluster, pts in Moderate and High Severity were more likely to be hospitalized (odds ratio = 1.77, p = 0.03); pts in High Severity cluster were more likely to die (hazard ratio = 2.23, p = 0.01). Conclusions: Unsupervised machine learning was able to partition pts into different PRO-CTCAE severity clusters; pts with higher baseline severity were more likely to be hospitalized or die. PRO-CTCAE provides additional information to GA. Funding: R01CA177592, U01CA233167, UG1CA189961.

PD-7 Updated survival analysis of the Danish randomized study comparing trifluridine/tipiracil with or without bevacizumab in patients with chemo-refractory metastatic colorectal cancer

Our investigator-initiated randomized trial in patients with chemorefractory metastatic colorectal cancer (mCRC) patients demonstrated improved PFS and OS in patients receiving bevacizumab combined with trifluridine/tipiracil (FTD/TPI) as compared with patients treated with FTD/TPI alone (Pfeiffer et al, Lancet Oncol 2020). In the present study, we have updated PFS and OS per February 1st, 2020. Furthermore, will evaluate markers for no benefit (1 month CT scan and increase in CEA), look for time to deterioration of performance status, and details regarding treatment-related hospitalization.

Real-World Assessment of Health Care Costs for Patients with Metastatic Pancreatic Cancer Following Initiation of First-Line Chemotherapy.

Management of metastatic pancreatic ductal adenocarcinoma (mPDA) places a significant financial burden on the U.S. health care system because of such factors as treatment with multidrug chemotherapy regimens, management of chemotherapy-related adverse events, and disease- or treatment-related hospitalizations. Depending on functional status, first-line chemotherapy regimens that are guideline recommended include nab-paclitaxel with gemcitabine (AG) and FOLFIRINOX (FFX), the combination of fluorouracil, leucovorin, irinotecan, and oxaliplatin. However, few previous studies have examined overall health care costs associated with mPDA management. To describe health care costs following initiation of first-line treatment with AG or FFX among patients with mPDA. Retrospective cohorts of first-line AG and FFX initiators were constructed from the MarketScan database (2014-2017). The index date was the date of first-line AG or FFX initiation. Included patients had insurance enrollment for 6 months before the index date. Total cumulative health care costs and costs from outpatient services, inpatient admissions, emergency department visits, chemotherapy administrations, and pharmacy dispensing were assessed within 12 months after the index date (i.e., 0-1, 0-2, …, 0-12 months). Patient-level cost data began accruing from the first paid claim and continued accruing until the censoring date. A total of 2,199 patients with mPDA initiated first-line AG (n = 1,352) or FFX (n = 847). Compared with AG initiators, FFX patients were younger (mean age 59 vs. 63 years) and had better baseline health status, with fewer having diabetes (43% vs. 57%) or coronary artery disease (12% vs. 22%). Median follow-up was 5.4 and 7.2 months for AG and FFX, respectively. Median first-line treatment duration was 2.1 months with AG and 2.3 months with FFX. Six months following first-line treatment initiation, total cumulative health care costs (median) were $85,714 (95% CI = $79,683-$91,788) and $114,116 (95% CI = $105,816-$119,591) for AG and FFX initiators, respectively. Outpatient services contributed the largest fractional cost for both groups. Total health care costs for patients with mPDA who initiated FFX or AG are driven mostly by outpatient rather than inpatient costs. Further research, using comparative methodology, is warranted to fully understand cost drivers and whether higher costs for FFX patients relate primarily to use of FFX or higher underlying use of outpatient care among FFX patients. This study was funded by Halozyme Therapeutics. Oestreicher and Yeganegi were employees of Halozyme Therapeutics at the time of the study and were involved in study design, data interpretation, and the decision to submit the data for publication. Bullock reports advisory board fees from Eisai, Exelixis, Bayer, and Taiho and consulting fees from Halozyme Therapeutics, outside the submitted work. Rowan reports consulting fees from Halozyme Therapeutics, during the conduct of the study. Chiorean reports grants and consulting fees from Celgene and Halozyme Therapeutics; grants from Lilly, Stemline, Ignyta, Roche, Merck, Boehringer-Ingelheim, Bristol Meyer Squibb, Incyte, Macrogenics, Rafael, and AADi; and consulting fees from Astra Zeneca, Array, Eisai, Ipsen, Five Prime Therapeutics, Seattle Genetics, Vicus, and Legend, outside the submitted work.