- Email: [email protected]
recurrent biliary tract cancer
abstracts months and the ORR were 37, 43, 14, 32% in MMR-D, EBVþ, HER2þ and all-negative groups, respectively. Twelve MMR-D pts received subsequent immune checkpoint inhibitors, which showed higher ORR (64%) and longer PFS (median PFS: 13.0 months) compared with earlier line chemotherapy. Conclusion: MMR-D might result in shorter PFS with first-line chemotherapy for AGC compared with other subgroups. Meanwhile immune checkpoint inhibitors achieved a longer PFS than standard chemotherapy in most MMR-D pts, supporting earlier use of immune checkpoint inhibitors.
O2 1 4
Kota Ouchi1,2, Shin Takahashi1,2, Akira Okita1, Yasuhiro Sakamoto3, Osamu Muto4, Kenji Amagai5, Takaho Okada6, Hisatugu Ohori7, Eiji Shinozaki8, Makio Gamou3, Chikashi Ishioka1,2 1 Department of Medical Oncology, Tohoku University Hospital, 2Department of Clinical Oncology, Institute of Development, Aging and Cancer (IDAC), Tohoku University, 3 Department of Medical Oncology, Osaki Citizen Hospital, 4Department of Medical Oncology, Akita Red Cross Hospital, 5Department of Gastroenterology, Ibaraki Prefectural Central Hospital, Ibaraki Cancer Center, 6Department of Digestive Surgery, Sendai Open Hospital, 7Department of Medical Oncology, Isinomaki Red Cross Hospital, 8 Gastrointestinal Oncology Department, The Cancer Institute Hospital of JFCR Background: Anti-EGFR antibody is one of the options for treatment of RAS wild-type metastatic colorectal cancer (mCRC), especially when the primary tumor site locates in the left sided large intestine. We have shown that methylation status evaluated by genome-wide DNA methylation test correlates with clinical outcomes of anti-EGFR treatment in RAS wild-type mCRC. Here, we report about the development of novel in vitro diagnostics (IVD) based on DNA methylation status of selected CpG sites. Method: We retrospectively collected KRAS wild-type mCRC cases who received antiEGFR treatment in salvage line. DNA methylation status was measured for 16 CpG sites by our novel IVD using real-time PCR method for each case. Based on DNA methylation status, they were classified into 2 groups. Highly-methylated colorectal cancer (HMCC) was defined when 8 or more sites among 16 sites were methylated and lowmethylated colorectal cancer (LMCC) was classified when it was less than 8 sites. We compared the clinical outcomes between the 2 groups, and the predictive accuracy of the DNA methylation status by the new diagnostic method was examined. Results: A total of 83 cases were collected, with 20 cases classified as HMCC and 63 cases classified as LMCC. The response rate of the anti-EGFR treatment was 5.0% (1/20 cases) in HMCC and 30.2% (19/63 cases) in LMCC, respectively (p ¼ 0.032). The median progression-free survival were 2.8 months and 5.3 months, respectively (p < 0.001, HR ¼ 0.33), and the median overall survival was 5.9 months and 14.1 months respectively (p < 0.001, HR ¼ 0.31). Conclusion: DNA methylation status of the 16 CpG sites measured by our novel IVD was significantly correlated with the therapeutic effect of anti-EGFR treatment for KRAS wild-type mCRC. Currently, extended analysis is in progress using the data of more than 200 cases. We will report the results including the analysis of RAS status and primary tumor site.
O2 2 2
A multicenter retrospective study of GEM1nab-PTX or FOLFIRINOX in metastatic pancreatic cancer patients: NAPOLEON study
Yujiro Ueda1, Taiga Otsuka2, Mototsugu Shimokawa3, Futa Koga4, Junichi Nakazawa5, Satoshi Ootsu6, Shiho Arima7, Masaru Fukahori8, Akitaka Makiyama9, Hiroki Taguchi10, Takuya Honda11, Taro Shibuki12, Tsuyoshi Shirakawa13, Kenji Mitsugi14, Kenta Nio15, Yasushi Ide16, Norio Ureshino2 1 Department of Hematology and Oncology, Japanese Red Cross Kumamoto Hospital, 2 Department of Medical Oncology, Saga-ken Medical Center Koseikan, 3Clinical Research Institute, National Kyushu Cancer Center, 4Department of Hepato-biliary-pancreatic medicine, Saga-ken Medical Centre Koseikan, 5Department of Gastroenterology and Hepatology, Kagoshima City Hospital, 6Department of Medical Oncology and Hematology, Oita University Faculty of Medicine, 7Digestive and Lifestyle Diseases, Kagoshima University Graduate School of Medical and Dental Sciences, 8Department of Medicine, Division of Gastroenterology, Kurume University Hospital, 9Department of Hematology/Oncology, Japan Community Healthcare Organization Kyushu Hospital, 10 Department of Gastroenterology, Saiseikai Sendai Hospital, 11Department of Gastroenterology and Hepatology, Nagasaki University Graduate School of Biomedical Sciences, 12Department of Gastroenterology, Imari Arita Kyoritsu Hospital, 13 Department of Medical Oncology, Fukuoka Wajiro Hospital, 14Department of Medical Oncology, Hamanomachi Hospital, 15Department of Medical Oncology, Sasebo Kyosai Hospital, 16Department of Internal Medicine, Japanese Red Cross Karatsu Hospital Background: Gemcitabine plus nab-paclitaxel (GnP) and FOLFIRINOX (FFX) are both considered as standard chemotherapy for patients with metastatic pancreatic cancer (mPC). However, there are no prospective clinical trials that directly compare these two therapies. We investigate and compare them to support the treatment selection for mPC. Methods: We retrospectively analyzed the patients with mPC who had received GnP or FFX as first-line chemotherapy at 14 institutions in Kyushu. In this study,
vi86 | Oral Session : Oral Abstracts Session
patient characteristics and clinical outcomes; overall survival (OS), progression-free survival (PFS), overall response rate (ORR), disease control rate (DCR) and adverse events (AEs) were compared. Results: A total of 211 pts were included; GnP 119 pts (73 males and 46 females) and FFX 92 pts (55 males and 37 females). The median age of the FFX group was younger than that of GnP (GnP 68 vs. FFX 61 years). There was neither significant difference in the OS (median: 10.2 vs. 11.1 months, HR 0.98, 95%CI 0.721.34, p ¼ 0.91) nor the PFS (median: 5.5 vs. 5.7 months, HR 1.05, 95%CI 0.79-1.40, p ¼ 0.75) between the GnP and FFX group, respectively. Moreover, neither significant difference in the ORR (29% vs. 27%, p ¼ 0.72) nor the DCR (81% vs. 79%, p ¼ 0.25) was seen. There were no significant differences in grade 3/4 neutropenia (55% vs. 58%) and febrile neutropenia (10% vs. 13%). Grade 3/4 peripheral sensory neuropathy (12% vs. 3%) and fatigue (4% vs. 0%) were more frequent with GnP. All grades of rash and alopecia were more frequent with GnP. Otherwise, grade 3/4 anorexia (6% vs. 20%), diarrhea (0% vs. 11%) and nausea (3% vs. 11%) were more with FFX. 64% of the patients with FFX received GnP as second-line, but the rate of patients with FFX followed by GnP was only 10%. Conclusions: There was no significant difference in the effectiveness between GnP and FFX statistically. We need to select the appropriate treatment for each patient, considering that the toxicity profiles differ.
O2 2 3½Encore
Phase II trial of GEMOX for the advanced pancreatic cancer with family/personal history of HBOC related cancer
Hidetaka Tsumura1, Chigusa Morizane2, Shogo Nomura2, Hideaki Takahashi3, Naohiro Okano4, Nobumasa Mizuno5, Hironaga Satake6, Kunihiro Tsuji7, Kazuhiko Shioji8, Akinori Asagi9, Kohichiroh Yasui10, Hiroyuki Miyakawa11, Atsushi Ishiguro12, Takashi Ogura13, Makoto Ueno14, Kazutoshi Tobimatsu15, Takeshi Terashima16, Masafumi Ikeda3, Takuji Okusaka2, Junji Furuse4 1 Hyogo cancer center, 2National Cancer Center Hospital, 3National Cancer Center Hospital East, 4Kyorin University Faculty of Medicine, 5Aichi Cancer Center Hospital, 6 Kobe City Medical Center General Hospital, 7Ishikawa Prefectural Central Hospital, 8 Niigata Cancer Center Hospital, 9National Hospital Organization Shikoku Cancer Center, 10Kyoto Prefectural University of Medicine, 11Sapporo Kosei General Hospital, 12 Teine Keijinkai Hospital, 13St. Marianna University School of Medicine, 14Kanagawa Cancer Center, 15Kobe University Graduate School of Medicine, 16Kanazawa University Background: A family and personal history of breast (B), ovarian(O), and pancreatic(P) cancer was reported to be a predictive marker in patients with pancreatic adenocarcinoma (PA) treated with platinum-based chemotherapy. We planned a prospective phase II trial to evaluate the efficacy and safety of platinum-based chemotherapy in this population. Method: Eligible patients had chemotherapy-naı¨ve metastatic PA, had one or more of the followings: 1) at least one family history of P/B/O/prostate (PR) cancer in a firstdegree relative, 2) at least two family members with history of P/B/O/PR cancer within third-degree relatives, and 3) at least one personal history of B/O/PR cancer.Patient suitable for FOLFIRINOX or gemcitabine plus nab-paclitaxel were ineligible unless patient refuse those regimens. Patients received gemcitabine 1000mg/m2and oxaliplatin 100 mg/m2 every two weeks (GEMOX). The primary endpoint was the one-year survival rate and 44% were desired. The sample size was calculated to be 43 pts, with a onesided alpha of 5% and a power of 80%. Results: A total of 45 pts were enrolled. First 43 pts were included in primary analysis. One-year survival rate was 27.9 [90%CI;17.0-41.3]% and didn’t met pre-planned boundary. Response rate was 27.9%. Tendency of prolonged survival was observed in patients with two or more family histories of P/B/O/PR cancer (HR 0.65, 95%CI [0.341.23]). Family history or personal history with B/O/PR cancer tended to be associate with better response and prolonged survival. In this study, patient with family history of pancreatic cancer seemed to be associate with poor response. The most common adverse events of grade 3 or higher were neutropenia (36%), leukopenia (27%), thrombocytopenia (23%) and elevated level of ALT (20%). Treatment related death was not observed. Conclusion: GEMOX did not show expected efficacy in patients with metastatic PA with family history or personal history of P/B/O/PR cancer.
O2 2 4
Phase I study of nivolumab or nivolumab/cisplatin/gemcitabine to treat unresectable/recurrent biliary tract cancer
Chigusa Morizane1, Masafumi Ikeda2, Makoto Ueno3, Satoshi Kobayashi3, Izumi Ohno2, Shunsuke Kondo1, Naohiro Okano4, Keisuke Kimura5, Suguru Asada5, Yoshinobu Namba5, Takuji Okusaka1, Junji Furuse4 1 National Cancer Center Hospital, 2National Cancer Center Hospital East, 3Kanagawa Cancer Center, 4Kyorin University Faculty of Medicine, 5Ono Pharmaceutical Co., Ltd Background: This open-label study in Japan evaluated the safety and efficacy of an immune checkpoint inhibitor nivolumab (NIVO) alone or with gemcitabine-cisplatin (NIVOþGC) to treat biliary tract cancer (BTC). We present updated results for longer follow-up (minimum:493 days; median:679 days). Methods: Patients with unresectable/recurrent BTC refractory or intolerant to gemcitabine-based treatment received NIVO (240 mg, 2-week intervals, N ¼ 30). Chemonaı¨ve patients with unresectable/recurrent BTC received the same NIVO
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Development of novel in vitro diagnostics to predict the efficacy of anti-EGFR treatment based on DNA methylation status
Annals of Oncology
abstracts
Annals of Oncology
O2 3 2
Phase 1 to 3 of the update of the EORTC Quality of Life Gastric module QLQ-STO22
Mitsumi Terada1, Samantha Sodergren2, Jane Blazeby3, Susanne Singer4, Takaki Yoshikawa5, Masanori Terashima6, Florian Lordick7, Vassilios Vassiliou8 1 medical department, EORTC, 2Faculty of Health Sciences, University of Southampton, 3 Bristol Centre for Surgical Research, Bristol Medical School, University of Bristol, 4 Institute of Medical Biostatistics, Epidemiology, and Informatics (IMBEI), University Medical Centre Mainz, 5Department of Gastric Surgery, National Cancer Center Hospital, 6Division of Gastric Surgery, Shizuoka Cancer Center, 7University Cancer Center Leipzig (UCCL), University Hospital Leipzig, 8Department of Radiation Oncology, Bank of Cyprus Oncology Centre Background: The EORTC QLQ-STO22 (STO22) was developed in 2001 to measure quality of life (QOL) of gastric cancer (GC) patients and is a well validated instrument. However, there are some points worth considering. Firstly, the treatment strategies have dramatically changed since 2001. In contrast to 20 years ago, diverse combination regimens with cytotoxic drugs and molecular agents are administered for advanced GC and multidisciplinary approaches including neoadjuvant therapy and minimally invasive surgery are the mainstay of treatment. Thus, the original STO22 might not adequately assess QOL of GC patients currently treated. Secondly, specialists and patients from East Asia were not involved in the development of the STO22. Consequently, QOL issues of East Asian patients might not be reflected in the original ST022. The EORTC QOL group in collaboration with the EORTC Gastrointestinal Tract Cancer Group and the JCOG, aim to update the existing STO22. Methods: Updating the STO22 consists of four steps. Pre-phase 1: literature review of studies using the ST022 in East Asia. Phase 1: Compiling an exhaustive list of relevant QOL issues captured from the literature review and interviews with patients and health care professionals. Phase 2: operationalising new issues into items to make a provisional module. Phase 3: Pilot testing the provisional updated ST022 alongside the EORTC QLQ-C30 with patients who meet the eligibility criteria from Europe and East Asia to obtain a response score for each item, together with a rating of relevance and importance. Results: This study is in progress and a grant application to the EORTC QOL group is under review. An interim report from pre-phase 1 and phase 1 will be presented at the congress. Conclusions: The current STO22 module might need updating to capture the QOL issues related to the new and diverse treatments and to include the East Asian perspective. The updated STO22 would be used more globally across Europe and Asia.
O2 4 1
Multidisciplinary team Management System for Adverse Events Occurring in New Cancer Immunotherapies
Miki Kondo1, Akiko Murayama1, Kazue Hayasaka1, Yukie Kimura2, Kenichi Miyamoto3, Hirohiko Yamauchi3,5, Junichiro Yuda3,5, Ryohei Serita4, Yasutoshi Kuboki5, Toshihiko Doi5 1 National Cancer Center Hospital East/Nursing Division, 2National Cancer Center Hospital East/Clinical Research Coordinator Section, 3National Cancer Center Hospital East/Hematology Department, 4National Cancer Center Hospital East/Intensive Care Unit, 5National Cancer Center Hospital East/Department of Experimental Therapeutics Introduction: Recently, promising efficacy has been reported for cell therapies using chimeric antigen receptor (CAR)-T cells, and bispecific T-cell engager antibody (BiTE) - a complex formed with antibodies against CD3 and antibodies against tumor cell surface antigens. However, severe adverse events such as cytokine release syndrome and neurotoxicity result in the incidence of high mortality, which is difficult to predict before initiating these therapies. These symptoms rapidly advance to the severe stage; therefore, a multidisciplinary team management system across the organization is necessary.
Volume 30 | Supplement 6 | October 2019
Method: Our multidisciplinary team developed standard operating procedure for adverse events. 1)Preparation of a symptoms checklist and action manual: A symptoms observation checklist and action manual (preparation of the tratment drugs and the treatment flow) were prepared for early detection and to decide on the early treatment approach. 2)Cooperation system with the intensive care unit: Admission and discharge criteria based on symptom severity were laid down. 3)Advance education: Training sessions were held for the expected responders, including holiday/night medical examinations (physicians, nurses, pharmacists, and research coordinators). 4)Communication system and information sharing: The communication system at the time of an event’s onset was clarified, and patient information was shared. Results: The actions decided could be implemented, and adverse events could be managed properly. Discussion: The careful construction of the management system prior to treatment implementation enables rapid action for the management of adverse events. As many more drugs will introduce into clinical practice in the future, it should be important to continue the verification and improvement of our system.
O2 4 2
Influence of physical symptoms on distress in patients with colorectal cancer undergoing outpatient chemotherapy
Miwa Aoki1, Harue Arao1, Akiko Hatakeyama1, Yoko Minamiguchi1, Masayo Toki2, Naomi Fujikawa3, Kota Asano4, Ayumi Takao2, Yukiko Tatsumi1 1 Osaka University Graduate School of Medicine, 2JCHO Osaka Hospital, 3Ishikawa Prefectural Central Hospital, 4Japanese Red Cross Society Kyoto Daini Hospital Objective: This study was performed to investigate the physical symptoms potentially affecting distress in patients with advanced and recurrent colorectal cancer and to consider nursing care for these patients. Methods: A self-administered questionnaire survey was given to patients with advanced and recurrent colorectal cancer undergoing outpatient chemotherapy in five hospitals. All outpatients met the study criteria and provided informed consent. The questionnaire included sociodemographic information and the Japanese version of the M. D. Anderson Symptom Inventory (MDASI-J). The items of distress on the MDASIJ were dependent variables, and the 11 symptom items were independent variables. Stepwise multiple regression was conducted using SPSS ver.25. Results: Responses were received from 76 patients (response rate: 95.0%). The patients’ mean age was 66.5 6 SD8.5 years, and 50 (65.8%) were male. Sixty-seven (88.2%) patients were undergoing surgery, and the median treatment period after relapse or metastasis was 12.0 (0-114) months. The mean MDASI-J score was 3.7 6 3.0 for numbness or tingling, 3.0 6 2.6 for fatigue, and 2.7 6 2.6 for drowsiness. Physical symptoms that affected the MDASI-J distress score were numbness or tingling, dry mouth, and lack of appetite (R2¼ 0.48, p<0.01). Discussion and Implication: About half of the distress in patients with advanced and recurrent colorectal cancer was explained by symptoms of numbness or tingling, dry mouth, and lack of appetite. We believe that the symptoms resulting in distress in patients with advanced and recurrent colorectal cancer were closely related to daily life, such as activities of daily living and meals. These findings suggest that medical staff should support the management of symptoms affecting activities of daily living, such as patients’ activities and meals, to help reduce distress in patients with advanced and recurrent colorectal cancer. This work was supported by KAKENHI Grant Number A16H055760.
O2 4 4
Improvement quality of life in elderly metastatic colorectal cancer patients receiving ambulatory chemotherapy
Phichai Chansriwong, Suwannee Sirilerttrakul, Nopakan Wannakansophon, Patamaporn Tangteerakoon, Suluck Vongterapak, Manmana Jirajarus, Sineenuch Ckumdee, Dittapol Muntham, Ekaphop Sirachainan Medical Oncology Unit, Internal medicine Department, Ramathibodi Hospital, Mahidol University, Thailand Background Thailand has become an aging society that consequence with the increasing in incidence of the elderly diagnosed with cancer including colon cancer. Chemotherapy remains the most suitable treatment for metastatic patients. Chemotherapy treatment that was once delivered only in hospital is now administered at patients home that helping patients to live normal lives during receiving chemotherapy. Chemotherapy regimens are based on a 48 hours 5 FU infusion combined that need patients to be hospitalized, resulted to decrease QOL and increase cost. Aims Compares the QOL score, patient satisfaction and cost difference in treating ambulatory chemotherapy or AC patients compared with inpatient treatment, and comparing between the elderly patients and younger patients. Methods Observational cohort which enrolled 156 patients at the Ramathibodi hospital from Dec 2015 to Nov 2016. AC administered by the central venous access device. The regimen as FOLFOX or FOLFIRI, 5 FU were in the elastomeric infusion pump and administered at the patient home. Nurse coordinators followed up with the patients by phone. The FACT G and FACT C scale, satisfaction and cost of treatment questionnaire were collected at time of enrolment, 2 months and end of treatment.
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regimen þ GC (N ¼ 30). Primary objectives were tolerability and safety. Overall survival (OS) and centrally assessed progression-free survival (PFS) and objective response rate (ORR) were secondary efficacy endpoints. Results: The most frequent drug-related adverse events with NIVO were decreased appetite (5/30, 17%), malaise (4/30, 13%), and pruritus (4/30, 13%), and with NIVOþGC w ere platelet count decreased (25/30, 83%) and neutrophil count decreased (25/30, 83%). In the NIVO cohort, median OS was 5.7 months (mo) (95% CI: 4.5, 8.7), median PFS was 1.4 mo (1.4, 1.4) and ORR was 10% (4, 23). Median OS was longer, and ORR higher, in the subgroup with programmed death-ligand 1 (PDL1) 1% in tumor-associated immune cells (TAIC) (n ¼ 19) than in those with PD-L1 <1% (n ¼ 10) (OS:8.3 mo [4.8, 9.4] vs 4.3 mo [3.1, 6.4]; ORR:16% [7, 34] vs 0% [0, 21]). In the NIVOþGC cohort, median OS was 13.8 mo (95% CI:12.2, 15.9), median PFS was 4.3 mo (4.0, 7.9), and ORR was 37% (24, 52). Median OS was longer, and ORR higher, in patients with PD-L1 1% (n ¼ 18) than in those with PD-L1 <1% (n ¼ 10) (OS:15.0 mo [12.2, 17.5] vs 13.0 mo [5.7, 15.4]; ORR:44% [27, 63] vs 20% [7, 46]). Median PFS was similar in the PD-L1 subgroups for both cohorts. Conclusion: Longer follow-up of patients with unresectable/recurrent BTC confirmed NIVO was well tolerated, with a manageable safety profile. Further data may show an association between PD-L1 expression in TAIC and longer OS with NIVO.
O2 1 4
Kota Ouchi1,2, Shin Takahashi1,2, Akira Okita1, Yasuhiro Sakamoto3, Osamu Muto4, Kenji Amagai5, Takaho Okada6, Hisatugu Ohori7, Eiji Shinozaki8, Makio Gamou3, Chikashi Ishioka1,2 1 Department of Medical Oncology, Tohoku University Hospital, 2Department of Clinical Oncology, Institute of Development, Aging and Cancer (IDAC), Tohoku University, 3 Department of Medical Oncology, Osaki Citizen Hospital, 4Department of Medical Oncology, Akita Red Cross Hospital, 5Department of Gastroenterology, Ibaraki Prefectural Central Hospital, Ibaraki Cancer Center, 6Department of Digestive Surgery, Sendai Open Hospital, 7Department of Medical Oncology, Isinomaki Red Cross Hospital, 8 Gastrointestinal Oncology Department, The Cancer Institute Hospital of JFCR Background: Anti-EGFR antibody is one of the options for treatment of RAS wild-type metastatic colorectal cancer (mCRC), especially when the primary tumor site locates in the left sided large intestine. We have shown that methylation status evaluated by genome-wide DNA methylation test correlates with clinical outcomes of anti-EGFR treatment in RAS wild-type mCRC. Here, we report about the development of novel in vitro diagnostics (IVD) based on DNA methylation status of selected CpG sites. Method: We retrospectively collected KRAS wild-type mCRC cases who received antiEGFR treatment in salvage line. DNA methylation status was measured for 16 CpG sites by our novel IVD using real-time PCR method for each case. Based on DNA methylation status, they were classified into 2 groups. Highly-methylated colorectal cancer (HMCC) was defined when 8 or more sites among 16 sites were methylated and lowmethylated colorectal cancer (LMCC) was classified when it was less than 8 sites. We compared the clinical outcomes between the 2 groups, and the predictive accuracy of the DNA methylation status by the new diagnostic method was examined. Results: A total of 83 cases were collected, with 20 cases classified as HMCC and 63 cases classified as LMCC. The response rate of the anti-EGFR treatment was 5.0% (1/20 cases) in HMCC and 30.2% (19/63 cases) in LMCC, respectively (p ¼ 0.032). The median progression-free survival were 2.8 months and 5.3 months, respectively (p < 0.001, HR ¼ 0.33), and the median overall survival was 5.9 months and 14.1 months respectively (p < 0.001, HR ¼ 0.31). Conclusion: DNA methylation status of the 16 CpG sites measured by our novel IVD was significantly correlated with the therapeutic effect of anti-EGFR treatment for KRAS wild-type mCRC. Currently, extended analysis is in progress using the data of more than 200 cases. We will report the results including the analysis of RAS status and primary tumor site.
O2 2 2
A multicenter retrospective study of GEM1nab-PTX or FOLFIRINOX in metastatic pancreatic cancer patients: NAPOLEON study
Yujiro Ueda1, Taiga Otsuka2, Mototsugu Shimokawa3, Futa Koga4, Junichi Nakazawa5, Satoshi Ootsu6, Shiho Arima7, Masaru Fukahori8, Akitaka Makiyama9, Hiroki Taguchi10, Takuya Honda11, Taro Shibuki12, Tsuyoshi Shirakawa13, Kenji Mitsugi14, Kenta Nio15, Yasushi Ide16, Norio Ureshino2 1 Department of Hematology and Oncology, Japanese Red Cross Kumamoto Hospital, 2 Department of Medical Oncology, Saga-ken Medical Center Koseikan, 3Clinical Research Institute, National Kyushu Cancer Center, 4Department of Hepato-biliary-pancreatic medicine, Saga-ken Medical Centre Koseikan, 5Department of Gastroenterology and Hepatology, Kagoshima City Hospital, 6Department of Medical Oncology and Hematology, Oita University Faculty of Medicine, 7Digestive and Lifestyle Diseases, Kagoshima University Graduate School of Medical and Dental Sciences, 8Department of Medicine, Division of Gastroenterology, Kurume University Hospital, 9Department of Hematology/Oncology, Japan Community Healthcare Organization Kyushu Hospital, 10 Department of Gastroenterology, Saiseikai Sendai Hospital, 11Department of Gastroenterology and Hepatology, Nagasaki University Graduate School of Biomedical Sciences, 12Department of Gastroenterology, Imari Arita Kyoritsu Hospital, 13 Department of Medical Oncology, Fukuoka Wajiro Hospital, 14Department of Medical Oncology, Hamanomachi Hospital, 15Department of Medical Oncology, Sasebo Kyosai Hospital, 16Department of Internal Medicine, Japanese Red Cross Karatsu Hospital Background: Gemcitabine plus nab-paclitaxel (GnP) and FOLFIRINOX (FFX) are both considered as standard chemotherapy for patients with metastatic pancreatic cancer (mPC). However, there are no prospective clinical trials that directly compare these two therapies. We investigate and compare them to support the treatment selection for mPC. Methods: We retrospectively analyzed the patients with mPC who had received GnP or FFX as first-line chemotherapy at 14 institutions in Kyushu. In this study,
vi86 | Oral Session : Oral Abstracts Session
patient characteristics and clinical outcomes; overall survival (OS), progression-free survival (PFS), overall response rate (ORR), disease control rate (DCR) and adverse events (AEs) were compared. Results: A total of 211 pts were included; GnP 119 pts (73 males and 46 females) and FFX 92 pts (55 males and 37 females). The median age of the FFX group was younger than that of GnP (GnP 68 vs. FFX 61 years). There was neither significant difference in the OS (median: 10.2 vs. 11.1 months, HR 0.98, 95%CI 0.721.34, p ¼ 0.91) nor the PFS (median: 5.5 vs. 5.7 months, HR 1.05, 95%CI 0.79-1.40, p ¼ 0.75) between the GnP and FFX group, respectively. Moreover, neither significant difference in the ORR (29% vs. 27%, p ¼ 0.72) nor the DCR (81% vs. 79%, p ¼ 0.25) was seen. There were no significant differences in grade 3/4 neutropenia (55% vs. 58%) and febrile neutropenia (10% vs. 13%). Grade 3/4 peripheral sensory neuropathy (12% vs. 3%) and fatigue (4% vs. 0%) were more frequent with GnP. All grades of rash and alopecia were more frequent with GnP. Otherwise, grade 3/4 anorexia (6% vs. 20%), diarrhea (0% vs. 11%) and nausea (3% vs. 11%) were more with FFX. 64% of the patients with FFX received GnP as second-line, but the rate of patients with FFX followed by GnP was only 10%. Conclusions: There was no significant difference in the effectiveness between GnP and FFX statistically. We need to select the appropriate treatment for each patient, considering that the toxicity profiles differ.
O2 2 3½Encore
Phase II trial of GEMOX for the advanced pancreatic cancer with family/personal history of HBOC related cancer
Hidetaka Tsumura1, Chigusa Morizane2, Shogo Nomura2, Hideaki Takahashi3, Naohiro Okano4, Nobumasa Mizuno5, Hironaga Satake6, Kunihiro Tsuji7, Kazuhiko Shioji8, Akinori Asagi9, Kohichiroh Yasui10, Hiroyuki Miyakawa11, Atsushi Ishiguro12, Takashi Ogura13, Makoto Ueno14, Kazutoshi Tobimatsu15, Takeshi Terashima16, Masafumi Ikeda3, Takuji Okusaka2, Junji Furuse4 1 Hyogo cancer center, 2National Cancer Center Hospital, 3National Cancer Center Hospital East, 4Kyorin University Faculty of Medicine, 5Aichi Cancer Center Hospital, 6 Kobe City Medical Center General Hospital, 7Ishikawa Prefectural Central Hospital, 8 Niigata Cancer Center Hospital, 9National Hospital Organization Shikoku Cancer Center, 10Kyoto Prefectural University of Medicine, 11Sapporo Kosei General Hospital, 12 Teine Keijinkai Hospital, 13St. Marianna University School of Medicine, 14Kanagawa Cancer Center, 15Kobe University Graduate School of Medicine, 16Kanazawa University Background: A family and personal history of breast (B), ovarian(O), and pancreatic(P) cancer was reported to be a predictive marker in patients with pancreatic adenocarcinoma (PA) treated with platinum-based chemotherapy. We planned a prospective phase II trial to evaluate the efficacy and safety of platinum-based chemotherapy in this population. Method: Eligible patients had chemotherapy-naı¨ve metastatic PA, had one or more of the followings: 1) at least one family history of P/B/O/prostate (PR) cancer in a firstdegree relative, 2) at least two family members with history of P/B/O/PR cancer within third-degree relatives, and 3) at least one personal history of B/O/PR cancer.Patient suitable for FOLFIRINOX or gemcitabine plus nab-paclitaxel were ineligible unless patient refuse those regimens. Patients received gemcitabine 1000mg/m2and oxaliplatin 100 mg/m2 every two weeks (GEMOX). The primary endpoint was the one-year survival rate and 44% were desired. The sample size was calculated to be 43 pts, with a onesided alpha of 5% and a power of 80%. Results: A total of 45 pts were enrolled. First 43 pts were included in primary analysis. One-year survival rate was 27.9 [90%CI;17.0-41.3]% and didn’t met pre-planned boundary. Response rate was 27.9%. Tendency of prolonged survival was observed in patients with two or more family histories of P/B/O/PR cancer (HR 0.65, 95%CI [0.341.23]). Family history or personal history with B/O/PR cancer tended to be associate with better response and prolonged survival. In this study, patient with family history of pancreatic cancer seemed to be associate with poor response. The most common adverse events of grade 3 or higher were neutropenia (36%), leukopenia (27%), thrombocytopenia (23%) and elevated level of ALT (20%). Treatment related death was not observed. Conclusion: GEMOX did not show expected efficacy in patients with metastatic PA with family history or personal history of P/B/O/PR cancer.
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Phase I study of nivolumab or nivolumab/cisplatin/gemcitabine to treat unresectable/recurrent biliary tract cancer
Chigusa Morizane1, Masafumi Ikeda2, Makoto Ueno3, Satoshi Kobayashi3, Izumi Ohno2, Shunsuke Kondo1, Naohiro Okano4, Keisuke Kimura5, Suguru Asada5, Yoshinobu Namba5, Takuji Okusaka1, Junji Furuse4 1 National Cancer Center Hospital, 2National Cancer Center Hospital East, 3Kanagawa Cancer Center, 4Kyorin University Faculty of Medicine, 5Ono Pharmaceutical Co., Ltd Background: This open-label study in Japan evaluated the safety and efficacy of an immune checkpoint inhibitor nivolumab (NIVO) alone or with gemcitabine-cisplatin (NIVOþGC) to treat biliary tract cancer (BTC). We present updated results for longer follow-up (minimum:493 days; median:679 days). Methods: Patients with unresectable/recurrent BTC refractory or intolerant to gemcitabine-based treatment received NIVO (240 mg, 2-week intervals, N ¼ 30). Chemonaı¨ve patients with unresectable/recurrent BTC received the same NIVO
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Development of novel in vitro diagnostics to predict the efficacy of anti-EGFR treatment based on DNA methylation status
Annals of Oncology
abstracts
Annals of Oncology
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Phase 1 to 3 of the update of the EORTC Quality of Life Gastric module QLQ-STO22
Mitsumi Terada1, Samantha Sodergren2, Jane Blazeby3, Susanne Singer4, Takaki Yoshikawa5, Masanori Terashima6, Florian Lordick7, Vassilios Vassiliou8 1 medical department, EORTC, 2Faculty of Health Sciences, University of Southampton, 3 Bristol Centre for Surgical Research, Bristol Medical School, University of Bristol, 4 Institute of Medical Biostatistics, Epidemiology, and Informatics (IMBEI), University Medical Centre Mainz, 5Department of Gastric Surgery, National Cancer Center Hospital, 6Division of Gastric Surgery, Shizuoka Cancer Center, 7University Cancer Center Leipzig (UCCL), University Hospital Leipzig, 8Department of Radiation Oncology, Bank of Cyprus Oncology Centre Background: The EORTC QLQ-STO22 (STO22) was developed in 2001 to measure quality of life (QOL) of gastric cancer (GC) patients and is a well validated instrument. However, there are some points worth considering. Firstly, the treatment strategies have dramatically changed since 2001. In contrast to 20 years ago, diverse combination regimens with cytotoxic drugs and molecular agents are administered for advanced GC and multidisciplinary approaches including neoadjuvant therapy and minimally invasive surgery are the mainstay of treatment. Thus, the original STO22 might not adequately assess QOL of GC patients currently treated. Secondly, specialists and patients from East Asia were not involved in the development of the STO22. Consequently, QOL issues of East Asian patients might not be reflected in the original ST022. The EORTC QOL group in collaboration with the EORTC Gastrointestinal Tract Cancer Group and the JCOG, aim to update the existing STO22. Methods: Updating the STO22 consists of four steps. Pre-phase 1: literature review of studies using the ST022 in East Asia. Phase 1: Compiling an exhaustive list of relevant QOL issues captured from the literature review and interviews with patients and health care professionals. Phase 2: operationalising new issues into items to make a provisional module. Phase 3: Pilot testing the provisional updated ST022 alongside the EORTC QLQ-C30 with patients who meet the eligibility criteria from Europe and East Asia to obtain a response score for each item, together with a rating of relevance and importance. Results: This study is in progress and a grant application to the EORTC QOL group is under review. An interim report from pre-phase 1 and phase 1 will be presented at the congress. Conclusions: The current STO22 module might need updating to capture the QOL issues related to the new and diverse treatments and to include the East Asian perspective. The updated STO22 would be used more globally across Europe and Asia.
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Multidisciplinary team Management System for Adverse Events Occurring in New Cancer Immunotherapies
Miki Kondo1, Akiko Murayama1, Kazue Hayasaka1, Yukie Kimura2, Kenichi Miyamoto3, Hirohiko Yamauchi3,5, Junichiro Yuda3,5, Ryohei Serita4, Yasutoshi Kuboki5, Toshihiko Doi5 1 National Cancer Center Hospital East/Nursing Division, 2National Cancer Center Hospital East/Clinical Research Coordinator Section, 3National Cancer Center Hospital East/Hematology Department, 4National Cancer Center Hospital East/Intensive Care Unit, 5National Cancer Center Hospital East/Department of Experimental Therapeutics Introduction: Recently, promising efficacy has been reported for cell therapies using chimeric antigen receptor (CAR)-T cells, and bispecific T-cell engager antibody (BiTE) - a complex formed with antibodies against CD3 and antibodies against tumor cell surface antigens. However, severe adverse events such as cytokine release syndrome and neurotoxicity result in the incidence of high mortality, which is difficult to predict before initiating these therapies. These symptoms rapidly advance to the severe stage; therefore, a multidisciplinary team management system across the organization is necessary.
Volume 30 | Supplement 6 | October 2019
Method: Our multidisciplinary team developed standard operating procedure for adverse events. 1)Preparation of a symptoms checklist and action manual: A symptoms observation checklist and action manual (preparation of the tratment drugs and the treatment flow) were prepared for early detection and to decide on the early treatment approach. 2)Cooperation system with the intensive care unit: Admission and discharge criteria based on symptom severity were laid down. 3)Advance education: Training sessions were held for the expected responders, including holiday/night medical examinations (physicians, nurses, pharmacists, and research coordinators). 4)Communication system and information sharing: The communication system at the time of an event’s onset was clarified, and patient information was shared. Results: The actions decided could be implemented, and adverse events could be managed properly. Discussion: The careful construction of the management system prior to treatment implementation enables rapid action for the management of adverse events. As many more drugs will introduce into clinical practice in the future, it should be important to continue the verification and improvement of our system.
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Influence of physical symptoms on distress in patients with colorectal cancer undergoing outpatient chemotherapy
Miwa Aoki1, Harue Arao1, Akiko Hatakeyama1, Yoko Minamiguchi1, Masayo Toki2, Naomi Fujikawa3, Kota Asano4, Ayumi Takao2, Yukiko Tatsumi1 1 Osaka University Graduate School of Medicine, 2JCHO Osaka Hospital, 3Ishikawa Prefectural Central Hospital, 4Japanese Red Cross Society Kyoto Daini Hospital Objective: This study was performed to investigate the physical symptoms potentially affecting distress in patients with advanced and recurrent colorectal cancer and to consider nursing care for these patients. Methods: A self-administered questionnaire survey was given to patients with advanced and recurrent colorectal cancer undergoing outpatient chemotherapy in five hospitals. All outpatients met the study criteria and provided informed consent. The questionnaire included sociodemographic information and the Japanese version of the M. D. Anderson Symptom Inventory (MDASI-J). The items of distress on the MDASIJ were dependent variables, and the 11 symptom items were independent variables. Stepwise multiple regression was conducted using SPSS ver.25. Results: Responses were received from 76 patients (response rate: 95.0%). The patients’ mean age was 66.5 6 SD8.5 years, and 50 (65.8%) were male. Sixty-seven (88.2%) patients were undergoing surgery, and the median treatment period after relapse or metastasis was 12.0 (0-114) months. The mean MDASI-J score was 3.7 6 3.0 for numbness or tingling, 3.0 6 2.6 for fatigue, and 2.7 6 2.6 for drowsiness. Physical symptoms that affected the MDASI-J distress score were numbness or tingling, dry mouth, and lack of appetite (R2¼ 0.48, p<0.01). Discussion and Implication: About half of the distress in patients with advanced and recurrent colorectal cancer was explained by symptoms of numbness or tingling, dry mouth, and lack of appetite. We believe that the symptoms resulting in distress in patients with advanced and recurrent colorectal cancer were closely related to daily life, such as activities of daily living and meals. These findings suggest that medical staff should support the management of symptoms affecting activities of daily living, such as patients’ activities and meals, to help reduce distress in patients with advanced and recurrent colorectal cancer. This work was supported by KAKENHI Grant Number A16H055760.
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Improvement quality of life in elderly metastatic colorectal cancer patients receiving ambulatory chemotherapy
Phichai Chansriwong, Suwannee Sirilerttrakul, Nopakan Wannakansophon, Patamaporn Tangteerakoon, Suluck Vongterapak, Manmana Jirajarus, Sineenuch Ckumdee, Dittapol Muntham, Ekaphop Sirachainan Medical Oncology Unit, Internal medicine Department, Ramathibodi Hospital, Mahidol University, Thailand Background Thailand has become an aging society that consequence with the increasing in incidence of the elderly diagnosed with cancer including colon cancer. Chemotherapy remains the most suitable treatment for metastatic patients. Chemotherapy treatment that was once delivered only in hospital is now administered at patients home that helping patients to live normal lives during receiving chemotherapy. Chemotherapy regimens are based on a 48 hours 5 FU infusion combined that need patients to be hospitalized, resulted to decrease QOL and increase cost. Aims Compares the QOL score, patient satisfaction and cost difference in treating ambulatory chemotherapy or AC patients compared with inpatient treatment, and comparing between the elderly patients and younger patients. Methods Observational cohort which enrolled 156 patients at the Ramathibodi hospital from Dec 2015 to Nov 2016. AC administered by the central venous access device. The regimen as FOLFOX or FOLFIRI, 5 FU were in the elastomeric infusion pump and administered at the patient home. Nurse coordinators followed up with the patients by phone. The FACT G and FACT C scale, satisfaction and cost of treatment questionnaire were collected at time of enrolment, 2 months and end of treatment.
doi:10.1093/annonc/mdz339 | vi87
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regimen þ GC (N ¼ 30). Primary objectives were tolerability and safety. Overall survival (OS) and centrally assessed progression-free survival (PFS) and objective response rate (ORR) were secondary efficacy endpoints. Results: The most frequent drug-related adverse events with NIVO were decreased appetite (5/30, 17%), malaise (4/30, 13%), and pruritus (4/30, 13%), and with NIVOþGC w ere platelet count decreased (25/30, 83%) and neutrophil count decreased (25/30, 83%). In the NIVO cohort, median OS was 5.7 months (mo) (95% CI: 4.5, 8.7), median PFS was 1.4 mo (1.4, 1.4) and ORR was 10% (4, 23). Median OS was longer, and ORR higher, in the subgroup with programmed death-ligand 1 (PDL1) 1% in tumor-associated immune cells (TAIC) (n ¼ 19) than in those with PD-L1 <1% (n ¼ 10) (OS:8.3 mo [4.8, 9.4] vs 4.3 mo [3.1, 6.4]; ORR:16% [7, 34] vs 0% [0, 21]). In the NIVOþGC cohort, median OS was 13.8 mo (95% CI:12.2, 15.9), median PFS was 4.3 mo (4.0, 7.9), and ORR was 37% (24, 52). Median OS was longer, and ORR higher, in patients with PD-L1 1% (n ¼ 18) than in those with PD-L1 <1% (n ¼ 10) (OS:15.0 mo [12.2, 17.5] vs 13.0 mo [5.7, 15.4]; ORR:44% [27, 63] vs 20% [7, 46]). Median PFS was similar in the PD-L1 subgroups for both cohorts. Conclusion: Longer follow-up of patients with unresectable/recurrent BTC confirmed NIVO was well tolerated, with a manageable safety profile. Further data may show an association between PD-L1 expression in TAIC and longer OS with NIVO.