Storandt, Michael H.

507 Background: Lenvatinib, a multikinase inhibitor, is an FDA approved treatment for advanced hepatocellular carcinoma (HCC) in the first line setting. Atezolizumab and bevacizumab are considered new standard of care as first line therapy after results of the IMBrave 150 trial. Currently, we do not have data to suggest any second-line treatment after administration of immunotherapy. We describe the clinical outcomes in patients with advanced HCC who received lenvatinib following treatment with immunotherapy. Methods: We conducted a multicentric, retrospective analysis of patients with advanced HCC diagnosed between 2010 and 2021 at Mayo Clinic in Minnesota, Arizona, and Florida. The study was reviewed and approved by the intuitional review board. The primary outcomes were overall survival (OS) and progression free survival (PFS). Results: We identified 53 patients with advanced HCC who received lenvatinib following immunotherapy. Most patients (83%) were male. Median age at start of lenvatinib was 67 years old. Forty-two (79%) patients had a Child-Pugh score of A at diagnosis while 30 (58%) patients were still Child-Pugh A at time of lenvatinib initiation. Risk factors for HCC included Hep C (43%), alcohol use (34%), NASH (15%) and hepatitis B (7%). Forty-five (85%) patients received lenvatinib in the 2nd line and 8 (15%) patients received it as third line or later. At time of data extraction, 38 (72%) patients had died. Median PFS was 4 months (95% CI: 3 – 6) and median OS from time of lenvatinib initiation was 13 months (95% CI: 6 – 24). The most common adverse events of any grade included fatigue (53%), hypertension (37%), AST elevation (30%), anorexia (28%), bilirubin elevation (25%) and diarrhea (25%). Twenty-one (40%) patients experienced grade 3 or higher adverse events including hypertension (25%), confusion (6%), acute kidney injury (2%), hyperkalemia (2%), ALT elevation (2%), proteinuria (2%), arthralgia (2%), heart failure (2%), AST elevation (2%), bilirubin elevation (2%), palmar-plantar erythrodysesthesia (2%), oral mucositis (2%), weight loss (2%), hypothyroidism (2%), anorexia (2%), fatigue (2%) and diarrhea (2%). Seven patients stopped treatment due to adverse events: 1 for hypertension, 2 for confusion, 1 for heart failure, 2 for fatigue, and 1 for elevated bilirubin. Conclusions: The optimal sequencing of therapy for patients with advanced HCC following progression on immunotherapy remains unknown. We found that median OS was 13 months in patients who received lenvatinib after immunotherapy which is comparable to survival in other studies when used as first line therapy. Our experience demonstrates that patients may benefit from treatment with lenvatinib following initial progression on immunotherapy.

227 Background: Circulating tumor DNA (ctDNA) consists of small fragments of DNA released into the plasma from cancer cells. Tumor informed ctDNA testing by whole exome sequencing of the primary tumor coupled with multiplex polymerase chain reaction (PCR)-based next generation sequencing of cell free DNA in serum, can detect and quantify ctDNA, allowing for detection of minimal residual disease (MRD). Methods: We conducted a retrospective analysis of 120 patients with colorectal cancer who had at least one tumor-informed ctDNA MRD assay completed between May 6, 2019, and July 1, 2022, at Mayo Clinic, Rochester. Disease recurrence was defined as radiographic evidence consistent with recurrence with or without biopsy confirmation. Data are presented descriptively, including number of ctDNA assays completed, ctDNA positivity prior to disease recurrence, and ctDNA concordance with carcinoembryonic antigen (CEA). The study protocol was exempt after review by the Mayo Clinic Institutional Review Board. Results: One-hundred twenty patients were included in the study with median age at initial disease diagnosis of 67.0 years. Sixty-four percent were male and 94% were white. At time of initial diagnosis, 10 had stage I, 23 stage II, 60 stage III, and 25 stage IV disease. In 120 patients, 476 ctDNA assays were performed, and 110 recurrences were observed among 62 patients. There were 39 instances in which ctDNA was obtained prior to clinical detection of recurrence and of these, at least one ctDNA assay was positive in 28 cases (72%). CEA was obtained prior to recurrence in 88 instances and was elevated in only 39 cases (44%). Among 37 instances where both ctDNA and CEA testing were obtained prior to recurrence, ctDNA was positive in 27 cases (73%) while CEA was positive in 14 cases (38%). ctDNA was positive in 83% of recurrences involving liver and 62.5% of recurrences involving only the lungs. ctDNA and CEA positivity are shown by location of recurrence. ctDNA and CEA were discordant in 44% of instances in which the assays were completed within 2-weeks of each other. Results of a ctDNA assay impacted management decisions in 16% of cases. Conclusions: ctDNA detected 72% of recurrences with higher rates of detection in liver versus lung metastasis. ctDNA performed superiorly to serum CEA in detection of recurrence, suggesting a role in disease surveillance. However, ctDNA impacted disease management in only 16% of patients, suggesting need for better patient selection and further study for ctDNA-based disease management strategy (more details will be reported). [Table: see text]

(1) Background: Cabozantinib, a multikinase inhibitor, is approved by the Food and Drug Administration (FDA) for the treatment of advanced hepatocellular carcinoma (HCC) following progression on sorafenib. Recently, atezolizumab plus bevacizumab has been approved in the first line setting for advanced HCC and has become the new standard of care. Whether cabozantinib improves outcomes following progression on immunotherapy remains unknown. We describe the clinical outcomes following treatment with immunotherapy in patients with advanced HCC who received cabozantinib. (2) Methods: We conducted a multicentric, retrospective analysis of patients with advanced HCC diagnosed between 2010–2021 at Mayo Clinic in Minnesota, Arizona, and Florida who received cabozantinib. Median overall survival and progression free survival analyses were performed using the Kaplan–Meier method. Adverse events were determined using Common Terminology Criteria for Adverse Events (CTCAE). (3). Results: We identified 26 patients with advanced HCC who received cabozantinib following progression on immunotherapy. Median progression free survival on cabozantinib therapy was 2.1 months (95% CI: 1.3–3.9) and median overall survival from time of cabozantinib initiation was 7.7 months (95% CI: 5.3–14.9). (4) Conclusion: The optimal sequencing of therapy for patients with advanced HCC following progression on immunotherapy remains unknown. Our study demonstrates that patients may benefit from treatment with cabozantinib following progression on immunotherapy.

Abstract Background: Medical financial hardship, encompassing material, behavioral, and psychologic domains, is becoming an increasingly common consequence of illness in cancer patients. Identifying at-risk patients is the first step to develop proactive approaches to mitigate this problem. To try and address this need, Mayo Clinic Breast Disease Registry (MCBDR) is prospectively collecting data about financial concerns in addition to the usual sociodemographic and clinical information. Methods: We used data from Mayo Clinic Breast Disease Registry, a prospective cohort of consenting patients seen at Mayo Clinic Rochester within one year of initial breast cancer diagnosis. Participants completed baseline and annual follow-up surveys rating their financial concerns on a linear analogue scale from 0 (“none”) to 10 (“constant concerns”). We compared patient-reported financial concern at baseline to that on each patient’s most recent survey, with worsening concerns defined as a 1+-point increase. Logistic regression evaluated for predictors of worsening financial concerns. Results: 1,957 participants responded to financial concern questions on a baseline and at least one follow-up survey between 2015 and 2020. Mean age was 58.5 years (SD 12.5), and mean time between diagnosis and the most recent follow-up was 25.6 months (SD 16.2). 357 (18.2%) reported worsening financial concerns. Only lower baseline financial status was associated with a greater likelihood of worsening financial concerns (see Table). Conclusions: More than one in seven breast cancer survivors develop worsening financial concerns within 5-years of diagnosis, and those with less financial security at baseline appear to be most vulnerable. Funding: Breast Cancer Research Foundation (CLL) and NR015259 (KJR). Patient and tumor characteristics, compared by whether financial status worsened over time Full Cohort (n=1957) Worsening, ≥ 1-point change (n=357) Stable/Improved (n=1600) p value Full Cohort (n=1957) Worsening, ≥ 1-point change (n=357) Stable/Improved (n=1600) p value Age at diagnosis II or III 502 (25.7%) 98 (27.5%) 404 (25.3%) 0.239 ≤ 50 546 (27.9%) 105 (29.4%) 441 (27.6%) IV 67 (3.4%) 17 (4.8%) 50 (3.1%) 0.086 51-64 757 (38.7%) 136 (38.1%) 621 (38.8%) 0.562 Unknown 351 (17.9%) 65 (18.2%) 286 (17.9%) 0.536 ≥65 654 (33.4%) 116 (32.5%) 538 (33.6%) 0.506 ER and/or PR positive Race No/Unknown 482 (24.6%) 92 (25.8%) 390 (24.4%) White 1863 (95.2%) 337 (94.4%) 1526 (95.4%) Yes 1475 (75.4%) 265 (74.2%) 1210 (75.6%) 0.580 Non-white 24 (1.2%) 5 (1.4%) 19 (1.2%) 0.729 Her2 positive Other/Unknown/Choose not to respond 70 (3.6%) 15 (4.2%) 55 (3.4%) 0.478 No/Unknown 1746 (89.2%) 314 (88.0%) 1432 (89.5%) Educational status Yes 176 (9.0%) 37 (10.4%) 139 (8.7%) 0.321 Less than bachelor’s degree 880 (45.0%) 168 (47.1%) 712 (44.5%) Borderline 35 (1.8%) 6 (1.7%) 29 (1.8%) 0.898 Bachelor's degree or higher 1065 (54.4%) 187 (52.4%) 878 (54.9%) 0.384 Radiation Unknown 12 (0.6%) 2 (0.6%) 10 (0.6%) 0.832 No/Unknown 781 (39.9%) 140 (39.2%) 641 (40.1%) Financial status near time of diagnosis Yes 1176 (60.1%) 217 (60.8%) 959 (59.9%) 0.768 Pay bills, money for special things 1412 (72.2%) 244 (68.3%) 1168 (73.0%) Chemotherapy/targeted therapy Pay bills, no money for special things 367 (18.8%) 80 (22.4%) 287 (17.9%) 0.046 No/Unknown 1264 (64.6%) 221 (61.9%) 1043 (65.2%) Pay bills by making cuts 102 (5.2%) 19 (5.3%) 83 (5.2%) 0.729 Yes 693 (35.4%) 136 (38.1%) 557 (34.8%) 0.241 Unable to pay bills 56 (2.9%) 10 (2.8%) 46 (2.9%) 0.911 Hormone/endocrine therapy Unknown 20 (1.0%) 4 (1.1%) 16 (1.0%) 0.750 No/Unknown 710 (36.3%) 141 (39.5%) 569 (35.6%) Employment status at time of diagnosis Yes 1247 (63.7%) 216 (60.5%) 1031 (64.4%) 0.163 Employed full-time 462 (23.6%) 83 (23.2%) 379 (23.7%) Surgery type Employed part-time/unemployed/retired 525 (26.8%) 92 (25.8%) 433 (27.1%) 0.856 Lumpectomy 846 (43.2%) 145 (40.6%) 701 (43.8%) Not available 970 (49.6%) 182 (51.0%) 788 (49.3%) 0.716 Mastectomy 903 (46.1%) 165 (46.2%) 738 (46.1%) 0.535 Stage at time of diagnosis None/Unknown 208 (10.6%) 47 (13.2%) 161 (10.1%) 0.069 0 or I 1037 (53.0%) 177 (49.6%) 860 (53.8%) Citation Format: Michael H. Storandt, Urshila Durani, Daniela Stan, Nicole Larson, Charles Loprinzi, Fergus Couch, Janet E. Olson, Nandita Khera, Kathryn J. Ruddy. Financial hardship in breast cancer survivors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 1012.