Tolay, Sameer

736 Background: Patients with dMMR/MSI-H gastrointestinal (GI) cancer occasionally receive neoadjuvant immunotherapy (NIT) due to various clinical considerations. To systematically evaluate the outcome of these patients, we initiated the DREAM-GI national database, intending to harness real-world data to provide crucial insights into the outcomes, safety profile, and response patterns of dMMR/MSI-H GI cancer patients undergoing NIT. Herein, we present the initial findings. Methods: We developed a centralized database to collect de-identified clinical data from patients with dMMR/MSI-H GI cancers receiving NIT. We collected data retrospectively and prospectively through September 15, 2023. Results: The current report includes 50 patients with a median age of 67 years (range 32 to 90); 21 (42%) were female, 9 (18%) were Black, and the remaining were White. The cohort included the following tumor types- 31 (62%) colorectal, 7 (14%) gastroesophageal, and 12 (24 %) pancreaticobiliary. Most patients had localized disease (34, 68%), while the rest had oligometastatic disease. NIT consisted of pembrolizumab monotherapy in 40 (80%) patients, ipilimumab plus nivolumab in 8 (16%), and nivolumab plus chemotherapy in 2 (4%) patients. Most patients, 33 (66%), were treatment-naive. The median duration of NIT was 6 months (range: 1.5 to 55), with a time to best response of 3 months (range: 1.5 to 12). Among 47 evaluable patients, the best responses were as follows: an overall response rate of 75% (35/47), consisting of radiologic complete response (CR) in 20 (43%), pathologic CR in 4 (9%), and partial response in 11 (24%). The median progression-free survival and overall survival were not reached after a median follow-up of 14 months (range: 2-80), calculated from the date of the first immunotherapy dose to the last follow-up or death. Among 24 patients achieving CR, all remained progression-free after a median follow-up of 25.5 months (range: 3-80). Stable and progressive diseases were observed in 7 (15%) and 5 (10%) patients, respectively. Only 5 (10%) patients underwent surgery following NIT, with 4 (80%) achieving pathologic CR. The reasons for not proceeding with surgery were comorbidities in 40 (80%) patients, disease extent in 4 (8%), and patient refusal in 1 (2%). Out of the 12 patients who expired at the data cut-off, 1 was due to immunotherapy-related pneumonitis, 6 due to disease progression, and the remainder from underlying comorbidities. Conclusions: Our study underscores the remarkable response rates and durability of responses achieved with NIT in patients with dMMR/MSI-H GI cancers. Progression on NIT was infrequent. These real-world data support further investigation into non-operative approaches for patients with dMMR/MSI-H GI cancers.

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.