Citations

105 Background: Patients with potentially resectable dMMR/MSI-H colon cancer (CC) often receive neoadjuvant immunotherapy (IO) if co-morbid conditions or the extent of disease preclude upfront surgery. We investigated the outcome of such patients treated in a real-world setting. Methods: This is a single-center retrospective study that included patients with dMMR/MSI-H localized and oligometastatic CC receiving neoadjuvant IO between January 1, 2016, and July 31, 2022 with a data cut-off date of September 15, 2022. Electronic charts were reviewed to gather data on patient characteristics, tumor characteristics, detailed treatment, toxicity, treatment response, and survival. The response was assessed by radiologic studies, endoscopy, pathology in resected patients, and circulating tumor DNA. Results: The study included 24 patients with a median age of 69 years (range, 32 to 91); 12 (50%) patients were female, and 5 (21%) patients were African American. Among the patients included, 12 (50%) had localized CC (9 of whom had clinical stage III disease), and the rest had oligometastatic CC. The reasons for not undergoing upfront surgery were co-morbidity in 12 patients (50%), disease extent in 11 (46%), and both in 1 (4%). Four patients (17%) received the ipilimumab/nivolumab combination, and the rest received pembrolizumab. Most patients (63%) received IO in the first-line setting. The median duration of IO and the time to best response were 7.5 months (range, 2 to 55) and 3 months (range, 3 to 12), respectively. Among 23 evaluable patients, the overall response rate (ORR) was 74 % (17/23), with complete response (CR) in 13 (57%), and partial response (PR) in 4 (17%) patients. Response assessment is pending in 1 patient. Four patients (17%) had stable disease (SD), and 2 patients (8 %) experienced progressive disease (PD) on IO (1 with localized and the other with metastatic CC). The median progression-free survival (PFS) and overall survival (OS) did not reach for the whole group after a median follow-up of 12.5 months (range, 2 to 69 months), with 19/24 (79 %) patients remaining progression-free. Three patients underwent surgery with 2/3 achieving pathological CR. Among the 12 patients with localized CC, ORR was 73% (6 CR, 2 PR, 2 SD, 1 PD, and 1 assessment pending); median PFS and OS were not reached after a median follow-up of 9 months (range, 2 to 45) with 1 patient experiencing progression on IO at the time of data cut-off. No unexpected toxicity was observed. Conclusions: In this small cohort of patients with dMMR/MSI-H localized and oligometastatic CC, most patients showed deep and durable responses to neoadjuvant IO, obviating the need for surgery. Progression on IO was rare. This real-world data support investigating a non-operative paradigm in patients with dMMR/MSI-H localized and oligometastatic CC.

(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.

BACKGROUND A patient-derived organoid (PDO) platform may serve as a promising tool for translational cancer research. In this study, we evaluated PDO’s ability to predict clinical response to gastrointestinal (GI) cancers. METHODS We generated PDOs from primary and metastatic lesions of patients with GI cancers, including pancreatic ductal adenocarcinoma, colorectal adenocarcinoma, and cholangiocarcinoma. We compared PDO response with the observed clinical response for donor patients to the same treatments. RESULTS We report an approximately 80% concordance rate between PDO and donor tumor response. Importantly, we found a profound influence of culture media on PDO phenotype, where we showed a significant difference in response to standard-of-care chemotherapies, distinct morphologies, and transcriptomes between media within the same PDO cultures. CONCLUSION While we demonstrate a high concordance rate between donor tumor and PDO, these studies also showed the important role of culture media when using PDOs to inform treatment selection and predict response across a spectrum of GI cancers. TRIAL REGISTRATION Not applicable. FUNDING The Joan F. & Richard A. Abdoo Family Fund in Colorectal Cancer Research, GI Cancer program of the Mayo Clinic Cancer Center, Mayo Clinic SPORE in Pancreatic Cancer, Center of Individualized Medicine (Mayo Clinic), Department of Laboratory Medicine and Pathology (Mayo Clinic), Incyte Pharmaceuticals and Mayo Clinic Hepatobiliary SPORE, University of Minnesota-Mayo Clinic Partnership, and the Early Therapeutic program (Department of Oncology, Mayo Clinic).

PURPOSE Patients with advanced biliary tract cancers (BTCs) have a dismal prognosis. This multisite, single-institution study analyzed the efficacy and safety of immune checkpoint inhibitors (ICIs) in patients with advanced BTC. MATERIALS AND METHODS The prospectively maintained institutional database was searched for patients with advanced BTC. Electronic medical records of the patients with advanced BTC treated with an ICI that included programmed death-1 or programmed death-ligand 1 blockers were retrospectively reviewed to obtain data on patient characteristics, tumor characteristics including molecular biomarkers, detailed treatment, response characteristics, survival, and toxicities. The analysis included overall response rate, survival, and correlation between survival and molecular biomarkers. RESULTS The institutional database query identified 47 patients with advanced BTC who received at least one dose of an ICI; 11 (24%) patients in the first-line setting and the rest of the patients had refractory disease. The median age of the cohort was 62 years, and 51% were female. The overall response rate was 10.6%, with a disease control rate of 53.2%. The median progression-free survival (PFS) and overall survival were 3.6 months and 6.9 months, respectively. Biomarker analysis revealed improved PFS in patients with tumor mutational burden > 5 mutations per megabase (median PFS: 6.4 v 2.2 months; P = .0027). No unexpected adverse events were observed. CONCLUSION ICIs are well tolerated and have modest antitumor activity in patients with advanced BTC. The study result supports the exploration of tumor mutational burden as a potential predictive biomarker for response to ICIs in patients with advanced BTC.

6552 Background: Significant amounts of expensive oncology drugs are discarded resulting in waste and financial consequences for patients. Beginning in 2023, the Infrastructure Investment and Jobs Act (IIJA) will require drug manufacturers to refund Medicare for any single-use drugs where greater than 10% of the drug is wasted. We explored potential IIJA-associated savings through assessment of patterns in spending for discarded oncology agents between 2017-2020. Methods: We utilized the Medicare Part B Discarded Drug Units database from 2017-2020. Using J codes, we extracted spending and reimbursement data for discarded medications for antineoplastic and classical hematology therapies. The primary outcome was identification of therapies with high percentage of waste and the economic impact of retroactive application of the IIJA for discarded therapies. Results: Medicare Part B utilization data was extracted for a median 77 (64-152) oncologic therapies per year with median reimbursement for discarded treatments of $590 M ($566-616). From 2017-2020, bortezomib, romiplostim, and nab-paclitaxel were consistently among the top 5 therapies by value of wasted product. Pembrolizumab waste by value declined significantly after 2017 following transition to fixed dosing. In 2020, the top 5 therapies by value of wasted product were bortezomib, nab-paclitaxel, trastuzumab, romiplostim, and cabazitaxel with a value of $278 M. In 2020, the agents with the highest percentage of wasted product were bortezomib (27%), cabazitaxel (28%), decitabine (23%), topotecan (23%), and azacitidine (22%) with a collective discarded value of $160 M. Notably, these agents have weight-based dosing and single-use vials. Based upon the average number of drug claims per recipient and volume of product discarded, eliminating drug waste would allow an additional 6564 patients to receive treatment with discarded bortezomib. The number of additionally treated patients for the other top 5 agents: cabazitaxel (1216), decitabine (1509), topotecan (291), and azacitidine (2682). Retroactive application of IIJA policy would have impacted a median 20 (12-26) oncology agents resulting in median annual cost savings of $153 M (142-157) and the median annual spending on wasted oncology therapies would decline to $440 M (410-466). Conclusions: The IIJA would have yielded a median annual savings of $153 M in Medicare spending if applied retroactively. Given a 10% waste cutoff, a limited number of agents would be targeted by this legislation. In our study, we observe that drugs associated with weight-based dosing and single-use drug vials account for most drug waste. Strategies to minimize discarded units (through storage of unused product, approval of multi-dose vial formulations, or fixed-dose therapies) could yield substantial savings while enabling health equity in collaboration with communities with difficult access to these drugs.