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461 Background: In localized gastric cancer (GC), deficient mismatch repair (dMMR) tumors reportedly have a favorable prognosis. However, a potentially detrimental effect of the dMMR status was suggested in patients treated with adjuvant chemotherapy. It remains unclear whether the mismatch repair (MMR) status can impact clinical outcomes in patients with metastatic GC (mGC) receiving palliative chemotherapy. We examined the impact of the MMR status on survival outcomes of patients with HER2-negative mGC receiving first-line fluoropyrimidine plus platinum (FP) chemotherapy. Methods: We reviewed patients with histologically confirmed metastatic, recurrent, or locally advanced unresectable adenocarcinoma of the stomach or gastroesophageal junction receiving first-line FP chemotherapy between January 2015 and August 2018 at Asan Medical Center, Korea. MMR status was correlated with clinical characteristics and survival outcomes for patients with available MMR immunohistochemistry results. Results: Of 895 patients, we analyzed 543 with available MMR protein expression results, and dMMR was detected in 4.4% (n=24). Patients with dMMR exhibited a significantly higher median age than those with proficient MMR (pMMR) (64 vs. 58 years, p=0.044). No signet ring cell carcinoma (SRCC) was detected among dMMR tumors, whereas SRCC was found in 17.5% of pMMR tumors. Based on our prognostic model (Koo DH et al, 2011), only 4.2% of patients with dMMR were classified as the poor-risk group (vs. 16.8% of patients with pMMR, p=0.097). No significant difference in progression-free survival (PFS) was noted between patients with dMMR and pMMR tumors (median, 5.6 vs. 5.8 months, p=0.266). Patients with dMMR tumors tended to have better overall survival than those with pMMR tumors; this difference was not statistically significant (median, 17.9 vs. 12.2 months, p=0.183). In the good-risk subgroup, patients with dMMR tumors had a significantly worse PFS than those with pMMR tumors (median, 5.6 vs. 9.2 months, p=0.009); multivariate analysis revealed that MMR status was an independent factor for poor PFS in this subgroup. Conclusions: Survival outcomes of dMMR mGC did not differ from pMMR in patients who received first-line FP chemotherapy. However, in the good-risk subgroup, patients with dMMR tumors had a significantly shorter PFS than those with pMMR, suggesting a potentially reduced efficacy of cytotoxic chemotherapy in these patients.

4566 Background: Although chemotherapy has been suggested to have the potential to cause a detrimental effect on treatment outcomes of localized GC with MMR-D, it remains unclear whether chemotherapy for metastatic/recurrent/unresectable GC with MMR-D would also adversely affect the survival outcomes. Anti PD-1 antibody (Ab) showed remarkable efficacy in patients with MMR-D and is being actively investigated in combination with cytotoxic chemotherapy. Hence, we aim to evaluate the impact of MMR status on treatment outcomes of advanced GC. Methods: We reviewed our database to identify all patients with HER2 negative, metastatic, recurrent, and locally advanced unresectable GC who received FP doublet chemotherapy from January 2015 to August 2018. For those who had an available tumor tissue, MMR protein expression was assessed by immunohistochemistry (IHC) and correlated with clinical characteristics and treatment outcomes. Results: Out of 895 patients identified from the database, 543 underwent IHC testing for MMR. The median age was 58 years (range, 24 – 86) with male comprising 64.0%. Most patients had initially metastatic disease (n = 382, 70.3%) followed by recurrent (n = 127, 23.3%) and locally advanced unresectable disease (n = 34, 6.3%). MMR-D was found in 4.4% (n = 24) and associated with age ≥ 65 years (50% vs. 29.9%; P = 0.04) and signet ring cell histology (0% vs. 17.7%, P = 0.01). According to our prognostic model (Koo DH et al, 2011), only 4.2% of patients with MMR-D were classified as Poor-risk group (vs. 16.8% of patients with MMR-P, p= 0.10). In the Good-risk group, patients with MMR-D (n = 10) had significantly shorter median progression-free survival (PFS, 6.0 vs. 9.0 months, P = 0.05) and overall survival (OS, 10.1 vs 20.9 months, P = 0.047) compared to those with MMR-P (n = 188), while there was no significant difference in survival outcomes depending on MMR status in the Moderate and Poor-risk groups. In multivariate analysis for OS, MMR status was a significant prognostic factor for OS in Good-risk group GC patients. Conclusions: GC patients with MMR-D had poorer median PFS and OS than those with MMR-P on standard cytotoxic chemotherapy in the Good-risk group. Thus, for Good-risk GC patients with MMR-D, anti PD-1 Ab alone might be considered rather than combining cytotoxic chemotherapy. Further investigation with next-generation sequencing is in process to determine underlying molecular mechanisms and will be presented in ASCO 2020.

444 Background: Although adjuvant chemotherapy has been known to have a detrimental effect on MMR-D patients (pts) with resectable GC, it is unclear whether palliative chemotherapy for advanced GC would also adversely affect the survival outcome of MMR-D pts. Immune-checkpoint inhibitor (ICI) monotherapy was approved as a standard treatment for ≥ 3rd line of advanced GC and also showed a remarkable efficacy in MMR-D pts regardless of line of therapy. ICI is now being investigated in combination with 1st-line cytotoxic chemotherapy. Hence, we aim to evaluate the prognostic impact of MMR on cytotoxic chemotherapy in advanced GC. Methods: We reviewed our prospective database to identify pts with initally metastatic, recurrent and locally advanced unresectable GC who received F-P doublet from 2015 to 2018. MMR was assessed by immunohistochemistry with previously-collected tumor tissue and correlated with clinical characteristics and survival outcomes. Results: Out of 892 pts identified from the database, 543 underwent MMR test [382 initally metastatic (70.3%); 127 recurrent (23.3%); 32 locally advanced unresectable (6.3%)]. Median age was 58 years (range, 24–86) with male comprising 64.0%. MMR-D was found in 4.4% (n = 24) and associated with age ≥ 65 (50% vs 29.9%; P = 0.037), antrum-origin (62.5% vs 34.1%, P = 0.004) and well/moderately-differentiated histology (41.7% vs 25.8%, P = 0.110). According to our prognostic model (Koo DH et al, 2011), MMR-D pts were less likely to be classified into poor-risk group (4.2% vs 16.8%, P = 0.102). In good-risk group, MMR-D pts had significantly shorter PFS (6.0 vs 9.0 months, P = 0.045) and OS (10.1 vs 20.9 months, P = 0.047), while pts in moderate and poor risk group showed no difference in survival depending on MMR status. Conclusions: MMR-D GC showed significantly shorter PFS and OS on F-P doublet in good-risk pts and further investigation is needed to determine underlying molecular mechanisms. With the negative impact of MMR-D on the effect of cytotoxic chemotherapy, exclusion of MMR-D pts should be considered in future trials of ICI and cytotoxic chemothrapy combination.

689 Background: FOLFIRINOX is one of standard 1st-line regimens for patients (pts) with advanced PDAC. However, there is no globally established 2nd-line regimen after failure of FOLFIRINOX. Although gemcitabine-based regimens are recommended by multiple guidelines and widely used in daily practice, further analysis is needed to reveal the magnitude of clinical benefit with these regimens. Nab-P+Gem is another standard 1st-line regimen for PDAC, but there are limited data as 2nd-line therapy in PDAC. Therefore, we conducted multicenter retrospective analysis of 2nd-line nab-P+Gem after progression on FOLFIRINOX in pts with advanced PDAC. Methods: Between Feb 2016 and Feb 2019, a total of 103 pts with histologically documented PDAC who received nab-P+GEM after progression on 1st-line FOLFIRINOX were identified among 5 referral cancer centers in South Korea. Results: Median age was 60 years and 50 pts (49%) were male. All but one pts had ECOG performance status of 0-1 at the time of nab-P+GEM. At the time of nab-P+GEM, 25 (24%) and 78 (76%) patients had locally advanced and metastatic disease, respectively. Median overall survival (OS) and progression-free survival (PFS) with nab-P+GEM was 9.8 months (95% CI: 8.9-10.6) and 4.6 months (95% CI: 3.7-5.5), respectively. Among pts with measurable disease (n = 95), partial response and stable disease were achieved in 8 (8%) and 56 (54%), respectively. Median OS from the start of 1st-line FOLFIRINOX was 20.9 months (95% CI: 15.2-26.6). Most common adverse event of all grade was anemia (77%), followed by neutropenia (60%), fatigue (52%), thrombocytopenia (45%), and peripheral neuropathy (30%). Most common grade 3-4 adverse events were neutropenia (36%), anemia (9%), and peripheral neuropathy (8%). Conclusions: In medically fit pts with advanced PDAC who failed on 1st-line FOLFIRINOX, nab-P+GEM was effective and well tolerated as 2nd-line therapy.