Background The National Comprehensive Cancer Network's Rectal Cancer Guideline Panel recommends American Joint Committee of Cancer and College of American Pathologists (AJCC/CAP) tumor regression grading (TRG) system to evaluate pathologic response to neoadjuvant chemoradiotherapy for locally advanced rectal cancer (LARC). Yet, the clinical significance of the AJCC/CAP TRG system has not been fully defined. Materials and Methods This was a multicenter, retrospectively recruited, and prospectively maintained cohort study. Patients with LARC from one institution formed the discovery set, and cases from external independent institutions formed a validation set to verify the findings from discovery set. Overall survival (OS), disease‐free survival (DFS), local recurrence‐free survival (LRFS), and distant metastasis‐free survival (DMFS) were assessed by Kaplan‐Meier analysis, log‐rank test, and Cox regression model. Results The discovery set (940 cases) found, and the validation set (2,156 cases) further confirmed, that inferior AJCC/CAP TRG categories were closely /ccorrelated with unfavorable survival (OS, DFS, LRFS, and DMFS) and higher risk of disease progression (death, accumulative relapse, local recurrence, and distant metastasis) (all p < .05). Significantly, pairwise comparison revealed that any two of four TRG categories had the distinguished survival and risk of disease progression. After propensity score matching, AJCC/CAP TRG0 category (pathological complete response) patients treated with or without adjuvant chemotherapy displayed similar survival of OS, DFS, LRFS, and DMFS (all p > .05). For AJCC/CAP TRG1–3 cases, adjuvant chemotherapy treatment significantly improved 3‐year OS (90.2% vs. 84.6%, p < .001). Multivariate analysis demonstrated the AJCC/CAP TRG system was an independent prognostic surrogate. Conclusion AJCC/CAP TRG system, an accurate prognostic surrogate, appears ideal for further strategizing adjuvant chemotherapy for LARC. Implications for Practice The National Comprehensive Cancer Network recommends the American Joint Committee of Cancer and College of American Pathologists (AJCC/CAP) tumor regression grading (TRG) four‐category system to evaluate the pathologic response to neoadjuvant treatment for patients with locally advanced rectal cancer; however, the clinical significance of the AJCC/CAP TRG system has not yet been clearly addressed. This study found, for the first time, that any two of four AJCC/CAP TRG categories had the distinguished long‐term survival outcome. Importantly, adjuvant chemotherapy may improve the 3‐year overall survival for AJCC/CAP TRG1–3 category patients but not for AJCC/CAP TRG0 category patients. Thus, AJCC/CAP TRG system, an accurate surrogate of long‐term survival outcome, is useful in guiding adjuvant chemotherapy management for rectal cancer.

6000 Background: Camrelizumab plus gemcitabine and cisplatin (GP) showed promising preliminary anticancer activity as first line (1L) therapy in patients (pts) with recurrent or metastatic nasopharyngeal carcinoma (R/M NPC) in a phase 1 trial ( W Fang et al; Lancet Oncol 2018). Here, we compared the efficacy and safety of camrelizumab with placebo plus GP as 1L therapy for pts with R/M NPC in a phase 3 trial. Methods: Eligible pts with previously untreated R/M NPC were randomized (1:1) to receive either camrelizumab (200 mg on day 1) plus gemcitabine (1000 mg/m2 on days 1, 8) and cisplatin (80 mg/m2 on day 1) or placebo plus the same chemotherapy regimens intravenously Q3W for a maximum of 6 cycles, followed by maintenance therapy with camrelizumab or placebo. The primary end point was progression-free survival (PFS) per independent review committee (IRC). Secondary end points included investigator-assessed PFS, objective response rate (ORR), disease control rate (DCR), duration of response (DOR), overall survival (OS) and tolerability. This trial is registered with ClinicalTrials.gov, number NCT03707509. Results: From Nov 2018 to Nov 2019, 263 pts from 28 centers were randomized to camrelizumab plus GP (n = 134, camrelizumab arm) or placebo plus GP (n = 129, placebo arm). At data cutoff on Dec 31, 2020 (67.7% maturity), 178 IRC-assessed PFS events occurred, and the median follow-up was 15.6 months (range 1.3-25.5). The median PFS per IRC was 10.8 months (95% CI 8.5-13.6) in the camrelizumab arm and 6.9 (95% CI 5.9-7.9) in the placebo arm (HR 0.51 [95% CI 0.37-0.69]; one-sided P < 0.0001). Investigator-assessed PFS showed similar results. IRC-assessed ORR was 88.1% (95% CI 81.3-93.0) in the camrelizumab arm and 80.6% (95% CI 72.7-87.1) in the placebo arm, with a median DOR of 9.9 (95% CI 7.7-12.5) and 5.7 months (95% CI 5.2-6.9; HR 0.48 [95% CI 0.34-0.68]), respectively. The DCR was 96.3% (95% CI 91.5-98.8) in the camrelizumab arm and 94.6% (95% CI 89.1-97.8) in the placebo arm. 18-month PFS rate was 34.8% (95% CI 25.7-44.1) vs 12.7% (95% CI 6.8-20.5), respectively. OS benefit was observed in the camrelizumab arm vs placebo arm (median not reached vs 22.6 months; HR 0.67 [95% CI 0.41-1.11]). Grade ≥3 treatment-related adverse events (TRAEs) occurred in 93% of pts in the camrelizumab arm and 90% in the placebo arm. The most common grade ≥3 TRAEs were decreased white blood cell count (66% vs 70%), decreased neutrophil count (64% vs 65%), decreased platelet count (40% vs 40%), and anemia (39% vs 43%). None of the differences were statistically significant. The safety profile was as expected, with no new signals observed. Conclusions: Addition of camrelizumab to GP significantly prolonged PFS as 1L therapy for R/M NPC, with a manageable safety profile. These data suggest that first line treatment with camrelizumab plus GP could be a standard of care for R/M NPC. Clinical trial information: NCT03707509.

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