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Neoadjuvant immunotherapy in gastrointestinal tumors with mismatch repair deficiency: An institutional analysis
Background
Clinical trials have reported robust anti-tumor activity of immunotherapy (IO) in metastatic deficient mismatch repair (dMMR)/ microsatellite instability-high (MSI-H) solid tumors. However, data documenting the efficacy of IO as neoadjuvant therapy in localized, locally advanced, and oligometastatic dMMR/MSI-H gastrointestinal (GI) cancers are sparse. We performed a single-institution retrospective analysis to evaluate the efficacy of neoadjuvant IO in dMMR/MSI-H GI cancer patients.
Methods
The current study included histologically documented dMMR/MSI-H GI cancer patients aged >18 years who had localized, locally advanced, or oligometastatic disease and received neoadjuvant IO in a tertiary care cancer center between January 1, 2015 and December 31, 2021. Electronic medical records of the patients were reviewed to gather de-identified data on patient characteristics, tumor characteristics, treatment details, duration of IO, response to IO, and survival. The data cutoff date was March 15, 2022.
Results
The analysis included 28 patients with the following patient characteristics: median age- 62 years (range, 32-90); gender- male 15 (53 %) and female 13 (47%), race- Caucasian 21(75%), African American 7 (25%). The tumor types included adenocarcinomas of colon 18/28 (64%), pancreas 4/28 (14%), stomach 2/28 (7%), biliary tract 2/28 (7%), duodenum 1/28 (4%), and rectum 1/28 (4%). The stage distribution was as follows: stage II-1 patient (3%), stage III-17 (61%), and stage IV (oligometastatic disease)- 10 (36%). The surgery was not pursued upfront either because of the extent of the tumors or comorbid conditions precluding surgery. The IO consisted of pembrolizumab in 22 (79%) patients, ipilimumab and nivolumab combination in 4 (14%), and immunochemotherapy combination in 2 (7%). Of the 28 patients, 15 (54%) received IO in the first-line and the rest in the second-line setting. The overall response rate was 75% (21/28): 6 (21 %) radiologic complete responses (CR), 3 (11 %) pathologic CR (pCR), 11 (39%) partial responses, 1(4%) clinical CR (cCR), 5 (18%) stable disease, and 2 (6%) progressive disease. The median duration of IO was 6.5 months (range, 2 to 52), and the median time to best response was 4 months (range, 2 to 10). After a median follow-up of 11.5 months (range, 3-78) from the beginning of IO, the median progression-free survival and overall survival were not reached, and only 4 (14%) patients died. After neoadjuvant IO, 4 (14%) patients underwent surgery, and 3 out of 4 patients did not have a viable tumor in the surgical specimen. All 14 patients who had at least 12 months of follow-up from the beginning of IO remained progression-free. Adverse events (AEs) of any grade were seen in 10 (36 %) patients and 6 (21%) patients had grade > 3 AEs.
Conclusions
In this small cohort of patients with dMMR/MSI-H GI tumors, neoadjuvant IO was associated with a high response rate, including complete responses in a significant proportion of patients. Further studies are needed to examine neoadjuvant IO as a standard strategy for patients with locally advanced and oligometastatic dMMR/MSI-H GI cancers. Furthermore, neoadjuvant IO may potentially offer non-operative management in patients with localized and locally advanced dMMR/MSI-H GI cancers.
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosures
S. Chakrabarti: Honoraria (self): Natera Inc; Speaker Bureau / Expert testimony: Natera Inc. B. George: Honoraria (self): BMS; Advisory / Consultancy: BMS. All other authors have declared no conflicts of interest.
