Shah, Preksha

e16479 Background: Recent genomic data has demonstrated SBA to be a molecularly unique entity when compared to colon or gastric cancers. The ongoing SWOG 1922 randomized clinical trial is comparing FOLFIRI to ramucirumab/paclitaxel as the second-line treatment for metastatic SBA. We sought to further define the activity of taxane-based therapy in the largest collection of SBA patients treated with this therapy. Methods: A retrospective review of SBA patients treated with taxane-based chemotherapy from 1994 to 2024 at MD Anderson Cancer Center was performed. All patients had pathologic confirmation, received > 1 cycle of therapy, and had documented tumor response evaluation. Response was assessed by the treating physician based on the imaging studies and categorized as response, stable disease or progression. Patient demographics, clinical parameters, molecular data, and taxane treatment was reviewed. Kaplan-Meier survival analysis was performed to calculate time to progression (TTP) and overall survival (OS). Results: 70 SBA patients treated with taxane-based therapy were identified. The median age at diagnosis was 57 years (range 33-80 years), majority being male (59%) with primary tumor located at duodenum (44%), Jejunum (34%), Ileum (16%). The most common presenting metastatic site was peritoneum (39%), followed by liver (31%). The genomic status revealed mutations in the following genes: 62% TP53, 47% KRAS, 24% SMAD4, and 15% APC. Taxane treatment was single agent (nab-paclitaxel, paclitaxel, or docetaxel) in 29%, gemcitabine and taxane combination in 61% and other taxane-based combinations in 10%. Therapy was given in the metastatic setting as 2nd-line in 40%, 3rd-line in 33% and 4th-line or greater in 20%. Response status was response in 24%, stable disease in 26%, and progression in 50%. Median TTP was 3.1 months (95%CI: 2.0-4.2 months), and median OS was 8.7 months (95%CI: 7.4-10.1 months). Median TTP was similar between single agent (2.6 months) and gemcitabine-based combination (2.5 months) (p =0.75). Efficacy did not differ by line of therapy nor primary tumor site. Efficacy differed by TP53 mutation status: TP53 mutated vs wildtype (response 21% vs 43%, p = 0.02; median TTP 2.4m vs 4.9m, p = 0.013; median OS 7.3m vs 10.6m, p = 0.004). Conclusions: This retrospective study of 70 SBA patients confirms the activity of taxane-based therapy demonstrating a response rate of 24% and median TTP of 3.1 months. Though limited by sample size, TP53 mutations may represent a negative predictive marker for taxane-based therapy in SBA patients. These findings support the ongoing SWOG 1922 trial investigating taxane-based therapy as a second line for metastatic SBA.

e15628 Background: Total neoadjuvant therapy (TNT) with cytotoxic chemotherapy and chemoradiation followed by surgical resection is a standard treatment for locally advanced rectal cancer (LARC). In a limited number of LARC patients with deficient mismatch repair (dMMR), treatment with an immune checkpoint inhibitor (ICI) resulted in all patients achieving complete clinical response (cCR) (median follow-up of 29 months) such that radiotherapy and surgery were avoided. These and other data have resulted in the routine use of neoadjuvant ICI for dMMR LARC. Here we report a multicenter series of patients with dMMR LARC treated with neoadjuvant ICI. Methods: Adult patients (N = 21) with dMMR LARC who received neoadjuvant ICI at Mayo Clinic, MD Anderson Cancer Center, Duke University or University of Pittsburgh were identified from the electronic medical record (EMR) and relevant data were abstracted. All patients were staged with pelvic MRI; clinical response was evaluated by repeat pelvic MRI and sigmoidoscopy. Data were summarized using descriptive statistics. This study was approved by the Mayo Clinic IRB. Results: Patients with clinical stage I (n = 2), II (n = 3) or III (n = 15) dMMR LARC were treated with neoadjuvant PD-1 monotherapy (n = 20) or combination (n = 1, ipilimumab+ nivolumab). Median age was 46 years (IQR 39, 65), 15 (71%) were male, 10 (48%) had distal tumors, and 14 had Lynch Syndrome. Median duration of ICI treatment was 7 mos (IQR 6, 12); one patient remains on dostarlimab at data cut-off. Clinical complete response (cCR) was achieved in 11 (52%) patients, partial response (PR) in 7 (33%), stable disease (SD) in 1 (5%), and progressive disease (PD) in 2 (10%) patients. Median time from first dose of ICI to best clinical response was 6 mos (IQR 5, 8) months. All partial or non-responders received salvage TNT with (n = 6) or without (n = 3) surgery. At a median follow up of 19 mos (range 6 to 56), tumor regrowth occurred in 1 patient who was subsequently treated with TNT. Any grade immune-related adverse event occurred in 6 (29%) patients; one grade 3 hepatitis occurred in the patient on Ipi+Nivo (Table1). Conclusions: Neoadjuvant ICI treatment of dMMR LARC resulted in half of treated patients achieving cCR. Careful monitoring is necessary to identify non responders who will require salvage TNT. Patient characteristics and clinical response to ICI. ID Sex Age Stage ICI Response to ICI ID Sex Age Stage ICI Response to ICI 1 M 62 T3N+ Pembro cPR 12 M 37 T3N+ Pembro cCR 2 M 60 T2N0 Pembro cCR 13 M 41 T3N0 Pembro cCR 3 M 80 T2N0 Pembro cPD 14 M 46 T4N+ Pembro cPR 4 M 36 T3N+ Ipi+Nivo cCR 15 M 68 T3N+ Pembro cPR 5 M 57 T3N+ Dostarli cCR 16 M 77 T3N0 Pembro cPR 6 M 39 T3N+ Dostarli cPR 17 M 40 T4Nx Pembro cCR 7 F 44 T2N+ Dostarli cPD 18 F 35 T3N+ Dostarli cCR 8 M 74 T3N+ Pembro cCR 19 M 60 T2N+ Pembro cPR 9 M 43 T3N+ Nivo cCR 20 F 65 T3N+ Pembro cCR 10 F 81 T3N0 Dorstali cPR 21 F 39 T4N+ Dorstali cSD 11 F 32 T2N+ Pembro cCR