H. Taniguchi

Japanese Society of Medical Oncology Clinical Guidelines: RAS (KRAS/NRAS) mutation testing in colorectal cancer patients

The Japanese guidelines for the testing of KRAS mutations in colorectal cancer have been used for the past 5 years. However, new findings of RAS (KRAS/NRAS) mutations that can further predict the therapeutic effects of anti‐epidermal growth factor receptor (EGFR) antibody therapy necessitated a revision of the guidelines. The revised guidelines included the following five basic requirements for RAS mutation testing to highlight a patient group in which anti‐EGFR antibody therapy may be ineffective: First, anti‐EGFR antibody therapy may not offer survival benefit and/or tumor shrinkage to patients with expanded RAS mutations. Thus, current methods to detect KRAS exon 2 (codons 12 and 13) mutations are insufficient for selecting appropriate candidates for this therapy. Additional testing of extended KRAS/NRAS mutations is recommended. Second, repeated tests are not required for the detection; tissue materials of either primary or metastatic lesions are applicable for RAS mutation testing. Evaluating RAS mutations prior to anti‐EGFR antibody therapy is recommended. Third, direct sequencing with manual dissection or allele‐specific PCR‐based methods is currently applicable for RAS mutation testing. Fourth, thinly sliced sections of formalin‐fixed, paraffin‐embedded tissue blocks are applicable for RAS mutation testing. One section stained with H&E should be provided to histologically determine whether the tissue contains sufficient amount of tumor cells for testing. Finally, RAS mutation testing must be performed in laboratories with appropriate testing procedures and specimen management practices.

Propensity Score Analysis of Regorafenib Versus Trifluridine/Tipiracil in Patients with Metastatic Colorectal Cancer Refractory to Standard Chemotherapy (REGOTAS): A Japanese Society for Cancer of the Colon and Rectum Multicenter Observational Study

This article compares the efficacy between regorafenib and trifluridine/tipiracil in patients with metastatic colorectal cancer refractory to standard chemotherapy, who had access to both drugs, to determine whether a further prospective comparative trial should be conducted.

A Multicenter Clinical Phase II Study of FOLFOXIRI Plus Bevacizumab as First-line Therapy in Patients With Metastatic Colorectal Cancer: QUATTRO Study

Background FOLFOXIRI (Fluorouracil, folinate, oxaliplatin, and irinotecan) plus bevacizumab improved progression‐free survival (PFS) and overall survival in patients with metastatic colorectal cancer (mCRC), compared with FOLFIRI (fluorouracil, folinate, and irinotecan) plus bevacizumab, but significantly increased the incidences of adverse events. The efficacy and safety profiles of FOLFOXIRI plus bevacizumab in ethnic Asian patients have not been established yet. Patients and Methods This study was an open‐label, single‐arm, multi‐centered phase II prospective clinical trial in patients with mCRC who received FOLFOXIRI plus bevacizumab. The primary endpoint was the PFS rate at 10 months. Secondary endpoints included overall survival, response rate, and safety. Results A total of 69 patients received FOLFOXIRI plus bevacizumab as induction therapy and were assessed for efficacy and safety. The PFS rate at 10 months was 75.2% and the median PFS was 13.3 months. Complete response and partial response were achieved in 2 (2.9%) and 47 patients (69.1%), respectively. Grade 3 and 4 adverse events with incidence rates exceeding 20% were neutropenia (72.5%), hypertension (34.8%), leucopenia (33.3%), and febrile neutropenia (21.7%). Significantly more patients with grade 4 neutropenia had single‐heterozygous UGT1A1*1/*6 or *1/*28 (46.2%) than UGT1A1 wild‐type genotype (*1/*1) (13.3%) (P = .004). Conclusions FOLFOXIRI plus bevacizumab is considered an effective first‐line regimen that improves the outcome of patients with mCRC regardless of ethnicity. In Asian patients, utmost attention should be paid to the possible onset of severe neutropenia or febrile neutropenia attributed to different types of UGT1A1*6 and *28 polymorphism, when FOLFOXIRI plus bevacizumab is administered. Micro‐Abstract FOLFOXIRI plus bevacizumab is an effective for Asian metastatic colorectal cancer patients and the safety profile is manageable by adopting appropriate measures, even if severe neutropenia and febrile neutropenia develop at a higher frequency in ethnic Asian patients with UGT1A1*6 and *28 polymorphism.

A prospective survey of comprehensive score for financial toxicity in Japanese cancer patients: report on a pilot study

Background Financial toxicity (FT) has a negative impact on the quality of life and survival of patients with cancer. The comprehensive score for FT (COST) questionnaire is a tool to measure FT which has already been validated in patients with cancer in the United States. However, the feasibility and validity of assessing FT using the COST questionnaire have not been established in non-US healthcare settings, including that in Japan. Methods This is a prospective pilot survey to ascertain the feasibility of using the COST questionnaire to evaluate FT in Japanese patients with advanced solid cancer who had been receiving chemotherapy for at least 2 months. The COST questionnaire was translated into Japanese using Functional Assessment of Chronic Illness Therapy methodology. Results Of the 12 patients approached, 11 (92%) responded to the questionnaire. The median COST score was 22 (range, 6–29; mean ± SD, 20.18 ± 8.17). Five (45%) and two (18%) patients suffered grade 1 (COST score 14–25) and grade 2 (COST score 1–13) FT, respectively. The COST measure demonstrated good internal consistency with a Cronbach α of 0.87. Conclusions The COST measure demonstrated good feasibility in measuring FT in the Japanese healthcare setting. Despite the existing universal health insurance system and ceiling amount for high-cost medical expenses, some Japanese patients experienced meaningful FT during chemotherapy. A prospective study is already underway to confirm the preliminary results (UMIN: 000025043).

A phase II trial of prophylactic olanzapine combined with palonosetron and dexamethasone for preventing nausea and vomiting induced by cisplatin

To investigate the efficacy and safety of olanzapine in combination with palonosetron and dexamethasone for patients receiving cisplatin (≥50 mg/m2), because this antiemetic therapy has not been sufficiently examined in patients receiving cisplatin.

O1-17-2PROGNOSTIC IMPACT OF HER2 IMMUNOREACTIVITY IN HER2-POSITIVE GASTRIC CANCER TREATED WITH TRASTUZUMAB-BASED CHEMOTHERAPY

Abstract Background: Trastuzumab (Tmab) improves overall survival in patients with HER2+ advanced gastric cancer (AGC) when combined with fluorouracil (F) or capecitabine (X) and cisplatin (P). However, the clinicopathological features associated with better prognosis remain unclear. We retrospectively evaluated the factors associated with favorable outcomes in HER2+ AGC patients treated with Tmab-based first-line chemotherapy. Methods: Subjects included 47 HER2+ AGC patients who received Tmab-containing combination chemotherapy as first-line therapy at Aichi Cancer Center Hospital between June 2006 and September 2013. Factors associated with progression-free survival (PFS) and overall survival (OS) were investigated using Cox regression model analysis. IHC3+ or ISH+ tumors were defined as HER2+. Results: Patient characteristics were as follows: median age, 63 years (range 22-85); male, 75%; ECOG PS 0/1, 48/52%; previous gastrectomy, 27%; differentiated type histology, 51%; IHC0-1 + /IHC2 + /IHC3 + , 11/23/66%; metastatic sites, lymph node/peritoneum/liver/lung, 83/51/47/30%; multiple metastatic sites, 81%; and combined antitumor agents, X + P/S-1 + P/F + P, 83/13/4%. The response rate (RECIST ver1.1) was 69.1% (95% CI, 0.53-0.81), and the disease control rate was 97.9%. At median follow-up of 15.4 months, median PFS and OS were 7.6 months (95% CI, 5.4-9.4) and 22.0 months (95% CI, 14.8-29.2), respectively. Upon multivariate analysis, only IHC3+ status was associated with increased PFS (HR = 0.36; 95% CI, 0.17-0.75; P = 0.006). IHC3+ status was also marginally associated with increased OS (HR = 0.46; 95% CI, 0.20-1.04; P = 0.06). The median PFS for the IHC3+ and IHC0-2+ subgroups was 9.8 and 6.2 months (log-rank P = 0.003), respectively. The median OS for each subgroup was 24.5 and 15.6 months (log-rank P = 0.02), respectively. Conclusions: Strong immunoreactivity for HER2 may be a predictor for better outcomes in HER2-positive AGC treated with trastuzumab-based chemotherapy.

633PCOMPARISON OF SURGERY WITH DEFINITIVE CHEMORADIOTHERAPY FOR POTENTIALLY RESECTABLE ESOPHAGEAL CANCER: A PROPENSITY-SCORE ANALYSIS

ABSTRACT Aim: To compare the survival by surgery (S group) to that by definitive chemoradiotherapy (CRT: R group) among patients with potentially resectable esophageal squamous cell carcinoma. Methods: From January 2003 to June 2012, 564 consecutive patients were reviewed. Overall survival (OS) was analyzed using Kaplan-Meier method and propensity-score adjusted Cox proportional hazard models. The variables included in propensity score model were age, gender, performance status (PS), histologic grade, primary cancer site, cT, cN, cM, serum albumin, and year of treatment (3 groups). Results: Three hundreds forty-two patients was in S group and 222 patients was in R group. Of the S group, 243 had preoperative chemotherapy, 37 had postoperative chemotherapy, and 62 had no adjuvant therapy. All values in patient characteristics were significantly different between S and R groups except for gender (age ≥ 65 years, 42% vs. 58%; gender male, 85% vs. 88%; Cancer site Ut/Mt/Lt, 14/49/37% vs. 14/60/27%; PS 0/1, 28/72% vs. 37/63%; cT stage 1/2/3, 19/13/68% vs. 40/9/51%; cN stage 0/1/2/3, 22/57/21/0% vs. 36/41/22/1%; cStage 1/2/3/4, 10/29/51/9% vs. 27/23/36/14%). In both unadjusted and adjusted analysis, there were no significant differences in survival of patients with cT1 and cT2 stages individually between S and R groups (cT1, unadjusted hazard radio (uHR) 1.9, p = 0.15; adjusted hazard radio (aHR) 1.5, p = 0.38. cT2, uHR2.1, p = 0.20; aHR1.8, p = 0.39). The R group was associated with worse OS compared to S group in those with cT3 stage (uHR1.9, p = 0.001; aHR1.8, p = 0.003). While OS benefit of S group was detected for cStage III patients (uHR2.2, p Conclusions: Our study indicated CRT is comparable survival to surgery based therapy for patients with esophageal squamous cell carcinoma except for patients with cT3 or cStage III. Disclosure: All authors have declared no conflicts of interest.

Prognostic and predictive value of CA19-9 in metastatic colorectal cancer.

354 Background: CA19-9 has been approved by FDA as a tumor marker in pancreatic cancer. The prognostic and predictive value of CA19-9 in metastatic colorectal cancer (mCRC) is still unclear. Moreover, CA19-9, a sialyl Lewis A antigen, acts as an adhesion factor of cells lining the blood vessels, but the association between the CA19-9 value and the effect of bevacizumab (BV) has not been reported. Methods: We conducted a retrospective review of 239 patients undergoing first-line chemotherapy by oxaliplatin-based regimens at a single institution from April 2005 to December 2009. The relationship between the CA19-9 value at baseline and the various clinicopathological factors and survival data was analyzed. Results: Median age was 62 years (range 23–83 years). 133 patients had a baseline CA19-9 value above the normal upper limit (>50 U/ml, high group), 86 had ULN (<50 U/ml, normal group), and 20 had below measurement sensitivity (example of Lewis antigen negativity, low group). The rate of KRAS MT and BRAF M...