3518 Background: Rechallenge with anti-EGFR monoclonal antibody (EGFR mAb) showed certain activities in patients (pts) with RAS/ BRAF V600E wild-type (wt) metastatic colorectal cancer (mCRC), particularly in pts with negative plasma RAS (p RAS) mutation by circulating-tumor DNA (ctDNA) assay at ‘just before’ the rechallenge therapy. However, the efficacy is unknown in pts with RAS/ BRAF wt mCRC whose p RAS was converted to positive once during or after EGFR mAb. Therefore, we conducted REMARRY, a prospective longitudinal study to investigate the p RAS dynamics, and PURSUIT trials, a phase II trial to investigate the efficacy of EGFR mAb rechallenge in pts with p RAS wt just before rechallenge therapy. Methods: The eligibility criteria of REMARRY trial included RAS/ BRAF V600E wt mCRC; ECOG PS 0-1; CR or PR during EGFR mAb; and a refractory ≤ 2 months from the last administration of EGFR mAb. p RAS status by the BEAMing method was prospectively monitored at timepoints of progression on EGFR mAb and each subsequent therapy. The eligibility criteria of PURSUIT trial included enrollment in the REMARRY trial with confirmed p RAS wt prior to enrollment in PURSUIT trial; being refractory or intolerant to fluoropyrimidine, oxaliplatin, and irinotecan; and ≥ 4 months of EGFR mAb-free interval. Study treatment was rechallenge with panitumumab + irinotecan (6 mg/kg + 150 mg/m2 q2wks). Primary endpoint was a confirmed objective response rate (ORR) according to RECIST v1.1. The required number of pts was 45, with a null ORR of 10%, an expected ORR of 25%, power of 85%, and one-sided α of 0.05. Results: Between May 2019 and May 2021, 183 pts with 343 timepoints (median, 2) were enrolled in REMARRY trial from 27 institutions, and 50 pts were enrolled in PURSUIT trial; median age, 68 years; left-sided primary, 44 pts; prior EGFR mAb, 1st/2nd/≥3rd lines was 28/6/16 pts; and p RAS status at progression on prior EGFR mAb, wt/mutant (mt)/unknown in 31/7/12 pts. Confirmed ORR and disease control rate were 14% (90% CI, 7.8%–23.9%) and 80% (95% CI, 67.0%–88.8%), respectively. In addition, 4 pts showed an unconfirmed PR. With a median follow-up time of 8.7 months, median progression-free survival was 3.6 months (95% CI, 3.0 – 4.7 months). The subgroup analysis showed a significantly higher confirmed ORR in pts with a longer EGFR mAb-free interval than a shorter one (> vs. < 365 days, 44.4% vs. 7.3%, p = 0.0037). Without any unexpected safety signals, 58.5% of pts had ≥ grade 3 adverse events. Of 31 patients with wt p RAS at progression on prior EGFR mAb, 5 had a confirmed response (ORR, 16%), whereas no response was observed in patients with 7 p RAS mt (ORR, 0%) (p = 0.25). Conclusions: The primary endpoint of confirmed ORR was not met; however, pts with p RAS wt at progression on prior EGFR mAb may benefit from rechallenge with, implying a lack of or worse response if p RAS becomes positive even once during or after EGFR mAb. Clinical trial information: REMARRY: UMIN000036424 PURSUIT: jRCTs031190096.

Purpose Dysgeusia is an adverse event caused by chemotherapy. Although retrospective studies have shown zinc administration improves dysgeusia, there have been no prospective studies. The present study examined effects of zinc therapy on dysgeusia in patients with gastrointestinal cancer. Methods This multicenter, prospective, observational study enrolled patients with dysgeusia during chemotherapy treatment. Patients received no intervention (control), polaprezinc p.o., or zinc acetate hydrate p.o., and serum zinc levels were measured at 0 (baseline), 6, and 12 weeks. Dysgeusia was assessed using CTCAE v5.0 and subjective total taste acuity (STTA) criteria using questionnaires at baseline and 12 weeks. Results From February 2020 to June 2021, 180 patients were enrolled from 17 institutes. There were no differences in mean baseline serum zinc levels among the groups (67.3, 66.6, and 67.5 μg/dL in the no intervention, polaprezinc, and zinc acetate hydrate groups, respectively. P = 0.846). The changes in mean serum zinc levels after 12 weeks were − 3.8, + 14.3, and + 46.6 μg/dL, and the efficacy rates of dysgeusia were 33.3%, 36.8%, and 34.6% using CTCAE and 33.3%, 52.6%, 32.7% using STTA in the no intervention, polaprezinc, and zinc acetate hydrate groups, respectively. The STTA scores improved in all groups, with significant improvement observed in the polaprezinc group compared with the no intervention group (P = 0.045). Conclusion There was no significant correlation between the degree of serum zinc elevation and improvement in dysgeusia, suggesting that polaprezinc, but not zinc acetate hydrate, was effective in improving chemotherapy-induced dysgeusia. Trial registration. UMIN000039653. Date of registration: March 2, 2020.

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108 Background: In VOLTAGE-A, CRT (50.4 Gy with capecitabine of 1,650 mg/m2) followed by five cycles of consolidation Nivo (240 mg q2 weeks [W]) and radical surgery showed 30% of pathological complete response (pCR) in pts with MSS and 60% in MSI-H T3–4 NanyM0 LARC. Here, we report survival outcomes and functional results. Methods: All 39 MSS and 5 MSI-H pts were included in the VOLTAGE-A from Jan 2017 to Oct 2019. Survival outcomes, late adverse events, and patient-reported outcome measurements for urogenital and anal functions were analyzed. Urinary function was evaluated using the International Prostate Symptom Score (I-PSS) periodically at 1W, 1, 3, 6, and 12 months (M), postoperatively. Sexual function in sexually active male pts was evaluated using the International Index of Erectile Function (IIEF) score at 3, 6, and 12M, postoperatively. Anal function was evaluated using the Wexner score, low anterior resection syndrome (LARS) score, and fecal incontinence severity index (FISI) score at 1-year post-surgery. All functional scores were evaluated preoperatively. Results: With a median follow-up of 44.8M (range, 25.7-58.9M), the 3-year relapse-free survival (RFS) and 3-year overall survival (OS) rates were respectively 79.5% and 97.4% in MSS, and 100% each in MSI-H pts. Of the MSS pts, those with pCR, clinical CR (cCR) according to the MSKCC criteria, high PD-L1 expression (tumor proportion score [TPS] ≥1%), and CD8/eTreg ratios of ≥2.5 had a trend of better 3-year RFS and OS than those without. During the follow-up period, one patient developed CTCAE grade 3 immune-related colitis, which was diagnosed 20M after the last dose of Nivo. Postoperative functional results were acceptable in both populations; pre-surgical median I-PSS scores were 3, whereas postsurgical values were 5 (1W), 5.5 (1M), 5 (3M), 4 (6M), and 4 (12M); median IIEF score was 20 at pre-surgery and 6 (3M), 6 (6M), and 8 (12M) at post-surgery; median scores of Wexner, LARS, and FISI were 2, 23, and 7 at pre-surgery, and 9, 30, and 17 at 1-year post-surgery, respectively. Conclusions: Preoperative CRT followed by Nivo showed promising survival outcomes in both MSS and MSI-H LARC pts. The therapeutic effect of pCR, cCR, and certain biomarkers analyzed by pre-CRT samples could be used as prognostic predictors in MSS pts. Clinical trial information: NCT02948348 .[Table: see text]

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Comprehensive genomic profiling (CGP) tests have been covered by public insurance in Japan for patients with advanced solid tumors who have completed or are completing standard treatments or do not have them. Therefore, genotype-matched drug candidates are often unapproved or off-label, and improving clinical trial access is critical, involving the appropriate timing of CGP tests. To address this issue, we analyzed the previous treatment data for 441 patients from an observational study on