Peterson, Carrie Y.

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.

TPS234 Background: Total neoadjuvant therapy (TNT) followed by total mesorectal excision (TME) is one of the standard treatment options for patients with locally advanced rectal cancer (LARC). A commonly employed TNT protocol consists of 8 biweekly cycles of oxaliplatin-based chemotherapy (CT) followed by radiation concurrent with fluoropyrimidine-based chemotherapy (CRT) for about 6 weeks. During the TNT, patients undergo tumor response assessments periodically with standard modalities (SM) consisting of pelvic magnetic resonance imaging (MRI) and proctoscopic/endoscopic examination. The objective of the current protocol is to evaluate the feasibility of tumor response assessment by ctDNA in patients with LARC undergoing TNT. The present feasibility study is designed to collect preliminary data to evaluate if a subsequent larger validation study is justified. If ctDNA-based response assessment is validated, ctDNA can potentially replace at least some components of the SM (for example, MRI) as tumor response assessment by SM is often time-consuming, expensive, and poses logistical challenges. Methods: Patients with LARC undergoing TNT will be enrolled. After obtaining informed consent, venous blood samples will be obtained for ctDNA level measurements at the following time points: baseline (within 1 week before the CT begins), after 4 cycles of CT within +/- 5 days of the MRI study, after 8 cycles of CT within +/- 5 days of the MRI study, and 1 to 14 days before TME. ctDNA levels will be measured by a commercially available ctDNA assay (Signatera by Natera), and ctDNA response is defined as >90% drop in the ctDNA level after treatment compared to the baseline level. Tumor response will be evaluated after 4 and 8 cycles of CT by SM. Primary endpoint: correlation between the response rate (RR) assessed by ctDNA and by SM after 4 cycles of CT. Secondary endpoints: 1) correlation between the RR assessed by ctDNA and by SM after 8 cycles of CT, and 2) correlation between the ctDNA defined RR and the complete pathological response (pCR) rate. The trial will enroll 30 patients. To evaluate the primary endpoint, differences in ctDNA levels between the baseline and 4-cycles post-CT will be computed. The differences will then be expressed as a proportion of each patient’s baseline level, D. This relative change, D, will be compared between the responder and non-responder groups using a two-sample Welch’s t-test. Similar methods will be applied for the secondary endpoints. All analyses will use the nominal type I error level of 0.05 and two-sided tests. Clinical trial information: NCT04670588.