Background. KRAS is one of the most frequently mutated oncogenes in colorectal cancer (CRC). Recently, a novel therapy targeting KRAS G12C mutation has demonstrated promising activities for corresponding advanced solid tumors, including metastatic CRC (mCRC). However, the prognostic impact of the KRAS G12C mutation remains unclear in patients with mCRC. Materials and Methods. We retrospectively reviewed medical records of patients with mCRC who received first-line chemotherapy between January 2005 and December 2017 at four large oncology facilities in Japan. Survival outcomes were compared between patients with KRAS G12C and those with non-G12C mutations. Results. Among 2,457 patients with mCRC, 1,632 met selection criteria, and of these, 696 had KRAS exon 2 mutations, including 45 with KRAS G12C mutation tumors. Patient characteristics were not significantly different between the KRAS G12C and non-G12C groups. At a median follow-up of 64.8 months, patients with the KRAS G12C mutation showed significantly shorter first-line progression-free survival (PFS; median, 9.4 vs. 10.8 months; p = .015) and overall survival (OS; median, 21.1 vs. 27.3 months; p = .015) than those with non-G12C mutations. Multivariate analysis also showed that KRAS G12C mutation was significantly associated with shorter PFS (hazard ratio [HR], 1.43; 95% confidence interval [CI], 1.04-1.96, p = .030) and OS (HR, 1.42; 95% CI, 1.01-2.00; p = .044). Conclusion.We demonstrate that, compared with non-G12C mutations, KRAS G12C mutation is significantly correlated with shorter first-line PFS and OS. These findings indicate the relevance of a stratified treatment targeting KRAS G12C mutation in mCRC.

Chemoradiotherapy (CRT) with concurrent high-dose cisplatin (CDDP) is a standard treatment for locally advanced squamous cell carcinoma of the head and neck (LA-SCCHN). Docetaxel plus CDDP and 5-fluorouracil (TPF) induction chemotherapy (ICT) prior to CRT is considered for patients at high risk of distant metastases. The purpose of the current study was to evaluate the feasibility and efficacy of CRT with split-dose CDDP after TPF-ICT for LA-SCCHN. A total of 21 LA-SCCHN patients treated with TPF-ICT followed by concurrent CRT with split-dose CDDP between January 2011 and December 2017 were retrospectively analysed. The patients' characteristics were i) median age 66 years (48-75 years); ii) male/female, 21/0; iii) performance status 0-1/2, 20/1; iv) larynx/hypopharynx/oropharynx/oral cavity, 4/8/8/1 and v) clinical stage III/IV, 3/18. The numbers of TPF-ICT cycles 1/2/3 were 2/3/16. Median cumulative doses of CDDP in TPF-ICT and CRT were 180.0 and 206.7 mg/m 2 , respectively. All patients completed 70 Gy RT. The complete response rate was 76.2%. At a median follow-up of 51.5 months, median PFS and OS were not reached and 65.5 months, respectively. The most common grade 3 or worse toxicities during CRT-ICT were stomatitis (48%), dysphagia (21%), anorexia (17%) and leukopenia (14%). However, no grade 2 or worse nephrotoxicity, neurotoxicity or ototoxicity was observed. The results demonstrated that concurrent CRT with split-dose CDDP after TPF-ICT is feasible and effective for LA-SCCHN.

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84 Background: Although nivolumab (NIVO) and irinotecan (IRI) are recognized as standard third-line and further treatments for patients (pts) with advanced gastric cancer (AGC), the drug that should be administered first remains unclear. Conversely, tumor growth rate (TGR) during preceding treatment was associated with tumor response to regorafenib or trifluridine/tipiracil in colorectal cancer. Methods: We retrospectively evaluated 212 pts with AGC treated with NIVO or IRI for the first time between January 2015 and June 2018 at three institutions. The main inclusion criteria were ECOG PS of 0–2, prior use of fluoropyrimidines and taxanes, and no prior use of NIVO or IRI. Pts were classified into slow- (SG) and rapid- (RG) growing groups according to TGR and presence or absence of new lesions (NL) during preceding treatment. TGR = (D1 − D0)/100D0 (CT1 − CT0), where CT1 is the date of CT at PD during preceding treatment, CT0 is the date of CT before CT1, and Dn is the sum of target lesion diameters at CTn. SG and RG were defined as NL− with low TGR and NL− with high TGR or NL+, respectively. TGR cut-off value was defined as a median TGR of 0.30%/day. Results: A total of 117 pts (RG/SG, 72/45; NIVO/IRI, 32/85) were eligible. Almost all baseline characteristics were similar between the NIVO and IRI groups among the RG or SG, whereas the proportion of pts with peritoneum metastases was higher in the NIVO group than in the IRI group among the RG. The response rate (RR) was significantly higher with NIVO than with IRI [31% vs. 3%, odds ratio (OR): 13.8, p = 0.01; adjusted OR (aOR): 52, p = 0.002] among the SG, whereas it was comparable between both drugs (5% vs. 8%, OR: 0.68, p = 0.73; aOR: 0.94, p = 0.96) among the RG. PFS was longer with NIVO than with IRI [median PFS (mPFS) 4.2 vs. 1.9 months (m), hazard ratio (HR): 0.50, p = 0.10] among the SG, whereas it was shorter with NIVO than with IRI (mPFS 1.6 vs. 2.1 m, HR: 1.37, p = 0.28) in the RG. Conclusions: RR was higher with NIVO than with IRI among slow growing tumors, whereas it was comparable between both drugs among rapid growing tumors. TGR during preceding treatment might be helpful for drug selection in pts with AGC who are considered for treatment with NIVO or IRI.

SummaryBackground Combination therapy of gemcitabine with cisplatin (GC) is a standard first-line therapy for unresectable or recurrent biliary tract cancer (BTC). S-1 is often used as a second-line therapy in clinical practice, based on the results of some clinical studies investigating its efficacy and safety following gemcitabine monotherapy. However, few studies have reported on the clinical outcomes of S-1 following GC. The purpose of this study was to elucidate the efficacy and safety of S-1 following GC for unresectable and recurrent BTC. Methods We retrospectively collected the data of 116 patients (pts) who were treated with S-1 as a second-line therapy following GC for unresectable or recurrent BTC at Shizuoka Cancer Center (November 2009 to July 2019). Results Of these 116 pts., 84 were assessable. Patient characteristics were as follows: intrahepatic bile duct/extrahepatic bile duct/gallbladder cancer, 30/23/31 pts.; metastatic/recurrent/locally advanced, 57/17/10 pts. The median time to treatment failure and overall survival were 2.5 and 6.0 months, respectively. Among 65 pts. with measurable lesions, the overall response rate was 3.1% (2/65 pts) and the disease control rate was 24.6% (19/65 pts). The common grade 3/4 toxicities included anemia (12%), neutropenia (4%), infections (16%), fatigue (6%), and diarrhea (4%). Dose reduction or treatment schedule modification of S-1 was required in 29 pts. (34.5%), and 17 pts. (20%) terminated S-1 due to adverse events. Conclusions The efficacy and safety of S-1 following GC were almost the same as those of S-1 following GEM monotherapy for unresectable or recurrent BTC.