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Efficacy of chemotherapy following nivolumab in metastatic gastric cancer
abstracts
Annals of Oncology
P2 308
Successful treatment with osimertinib for leptomeningeal carcinomatosis from NSCLC with the EGFR T790M mutation
Naruo Yoshimura, Hidenori Takahashi, Emiko Kurosawa, Akiko Tanaka, Masahito Ebina, Takashi Ohrui Department of Pulmonology, Tohoku Medical And Pharmaceutical University Osimertinib is a third-generation tyrosine kinase inhibitor (TKI) of the epidermal growth factor receptor (EGFR) that has been approved for the treatment of metastatic non-small cell lung cancer (NSCLC) with EGFR mutation, and positive for the secondary T790M mutation of EGFR. In a preclinical study, it also showed efficacy against leptomeningeal carcinomatosis (LMC) derived from NSCLC resistant to first-generation and second-generation EGFR-TKIs. We report the case of a patient aged 55 years with symptomatic LMC derived from NSCLC. We detected T790M mutation of EGFR by liquid biopsy with blood sample. He showed a clinical and radiographic response to osimertinib.
P3 014
Maung Kyaw Maung Radiation Oncology Department, Yangon General Hospital, Yangon, Myanmar Background: Due to loco-regionally advanced at diagnosis, multi-modality treatment become optional for most of oesophageal cancer patients. With advanced imaging modalities and treatment machines, conformal radiotherapy with concurrent chemotherapy is the standard approach for non-surgical candidates. The aim of the present study was to assess immediate loco-regional response of neoadjuvant chemotherapy followed by concurrent chemoradiation therapy for oesophageal cancer patients. Methods: This study include histologically proven oesophageal cancer patients who are refuse or unfit for surgery or unresectable disease with performance status 0-2. Neoadjuvant chemotherapy 2 cycles with cisplatin and 5FU regime followed by concurrent chemoradiation therapy (3D CRT, 50 Gy over 5 weeks with single agent cisplatin 75 mg/m2 on day 1 and 21 of radiotherapy was given. Response assessment was done with CT scan and endoscopy at 6th week after RT. Written informed consent was obtained from all patients. Results: 26 patients were included in the study between August 2015 and December 2016. Commonest age group was within 5th to 7th decade of life. 16 were male (61.5%). 25 had SCCs (96.2%). 18 patient were with oesophageal cancer at middle third (69.3%). 15 present with grade III dysphagia (57.7%). 18 patients were stage III at the time of diagnosis. Total treatment compliance was 69.2%. During treatment, dysphagia grade revealed stable during first three weeks and worsened slightly over the last 2 weeks. During follow up period, 16 patients (61.5%) became free from dysphagia at 4th week and 19 patients (73.1%) at 6th weeks. On response assessment by CT and OGDS at 6th week, complete response was 15 (57.7%) and 18(69.3%) respectively and so overall response rate was 57.7%. Conclusion: This results support the feasibility of neoadjuvant chemotherapy followed by concurrent 3D CRT for oesophageal cancer patients with potential for a cure effect with acceptable toxicities.
P3 015 P2 310
Two cases of congestive heart failure during osimertinib treatment for EGFR mutant NSCLC
Satoshi Hara Respiratory Division, Department of Internal Medicine, Itami City Hospital We herein report two case of fatal congestive heart failure during osimertinib treatment for epidermal growth factor receptor (EGFR) mutant non-small cell lung cancer (NSCLC). Case1: A 66-year-old woman presented with progressive palpitation and dyspnea two months after starting osimertinib for the treatment of EGFR T790M-positive NSCLC. An echocardiogram demonstrated severe decreased left ventricular systolic function. She was diagnosed with fatal congestive heart failure caused by osimertinib treatment. Her general condition deteriorated, and she died three months after starting osimertinib. Case2: A 84-year-old woman was treated for recurrent EGFR mutant NSCLC after lobectomy, and osimertinib was administered. Severe exertional dyspnea appeared one month after starting osimertinib. She was also diagnosed with fatal congestive heart failure caused by osimertinib, and died for a few days. The causal relationship between osimertinib and cardiotoxicity has so far received little attention and thus remains unclear. Osimertinib inhibits HER2 (ERBB2) in addition to EGFR (ERBB1), thereby potentially causing cardiotoxicity.
P2 313
Clinical effect of alectinib in patients with ALK-positive non-small cell lung cancer
Koichi Nishi Department of Respiratory Medicine, Ishikwa Prefectural Central Hospital The clinical effect of alectinib (ALC) in patiets with ALK-positive non-small cell lung cancer was examined. The subjects were 8 ALK-positive non-small cell lung cancers who received ALC during the period from July 2014 to December 2018. The median age was 61.5 years old and all cases were adenocarcinomas. There were 5 cases of primary treatment administration, 2 cases of secondary treatment administration, 1 case of tertiary treatment administration. Response rate was 2 complete response (25.0%), partial response 3 cases (37.5%), disease stabilization 3 cases (37.5%), disease progress 0 cases (0%). Median progression-free survival after ALC administration was 212 days, median overall survival was 510 days, and good therapeutic effect was obtained. Also, no serious adverse events were observed.
Neoadjuvant Chemotherapy Followed by Concurrent Chemoradiation Therapy for Oesophageal Cancer Patients
Assessing the impact of sequence in delivering primary-directed palliative radiotherapy in esophageal cancer
Shaun Zhirui Ho, Yen Sin Koh, Michael Wang, Faye Lim, Francis Chin, Connie Yip, Tianrui Siow, Fuqiang Wang Division of Radiation Oncology, National Cancer Center Singapore, Singapore Background: The optimal sequence for primary-directed palliative radiotherapy in esophageal cancer is unknown. As the survival outcomes of these patients are poor, it is important to balance survival benefits from systemic chemotherapy against the benefits of primary-directed radiotherapy. Methods: We have retrospectively reviewed esophageal cancer patients who received palliative radiotherapy to the primary lesion and grouped them according to the sequence of treatment: chemotherapy followed by radiotherapy (C-RT), radiotherapy followed by chemotherapy (RT-C), or radiotherapy alone (RTa). We are interested in overall survival and the time spent on radiotherapy as a percentage of the time between start of radiotherapy to death (T-SPORT). Results: 92 patients receiving primary-directed radiotherapy were included in the study. Median overall survival in the C-RT and RT-C groups were 1.14 (0.82-1.72) and 0.95 (0.56-1.36) months respectively, which were significantly longer than the RTa group of 0.50 (0.38-0.74). On multivariate analysis, the groups receiving chemotherapy have similar hazard ratios when compared to RT alone (C-RT: HR 0.50 (0.30-0.84), p ¼ 0.008; RT-C: 0.51 (0.28 - 0.93), p ¼ 0.03). Median T-SPORT was 10.04% in C-RT group, similar to RTa group of 12.39%, whilst the RT-C group had the lowest value of 4.47%. Conclusion: We demonstrate that systemic chemotherapy has survival benefit regardless of sequence in the palliative management of esophageal cancer. Patients having primary-directed palliative radiotherapy before chemotherapy do not have worse overall survival. By having radiotherapy early, these patients spend a lower portion of remaining lifespan receiving radiotherapy, with subsequent more time to experience the benefits of treatment.
P3 027
Efficacy of chemotherapy following nivolumab in metastatic gastric cancer
Kohei Akiyoshi, Yuki Nakatani, Yuko Tsuboguchi, Yumi Yoshii, Shinya Ueda, Shunsuke Okazaki, Shinya Tokunaga, Haruko Daga Department of Medical Oncology, Osaka City General Hospital Background: Immuno-checkpoint inhibitors, nivolumab targeting programmed cell death 1 (PD-1) can result in significant benefit to gastric cancer. Some recent data about non-small cell lung cancer suggest anti-PD-1 therapy may enhance sensitivity to subsequent chemotherapy. To date, there are no reports on treatment efficacy after failure of PD-1 blockade in advanced gastric cancer. Therefore, we aimed to report the efficacy of chemotherapy after progressive disease on nivolumab.
Volume 30 | Supplement 6 | October 2019
doi:10.1093/annonc/mdz343 | vi139
Downloaded from https://academic.oup.com/annonc/article-abstract/30/Supplement_6/mdz343.102/5583023 by University of Cambridge user on 27 December 2019
Case 2: 72 y.o female contracted multiple lymphnode metastases and peritoneal dissemination of sigmoid colon cancer. She was treated by the following chemotherapies [FOLFOXþCET, FOLFIRIþBEV] and ALF was introduced in 3rd line. 3 courses of FOLFIRIþAFL were performed but the tumors were increased (PD). Case 3: 67 y.o female contracted unresectable rectal cancer and multiple lymphnode metastases. She was treated by the following chemotherapies [CAPOXþBEV, FOLFIRIþRAM] and ALF was introduced in 3rd line. 1 course of FOLFIRIþAFL was performed, but she deteriorated into bad condition and this therapy was stopped. Case 4: 64 y.o female contracted paraaortic lymphnode metastases of rectal cancer . He was treated by the following chemotherapies [FOLFOXþCET, FOLFIRIþBEV, FOLFIRIþPANI] and ALF was introduced in 4th line. 3 courses of FOLFIRIþAFL were performed but the tumors were increased (PD). Conclusion: Only Case1 showed tumor regression. But the other 3 cases those were treated by FOLFIRI þ molecularly targeted agents except AFL in previous line, showed no efficacy. It is suggested that only exchange of molecularly targeted agents to AFL in FOLFIRI therapy dose not show the enough antitumor effect in colorectal cancer.
abstracts
P3 029
Nab-paclitaxel plus ramucirumab combination therapy as secondline with advanced gastric cancer:Retrospective study
Tomomi Kashiwada, Atsujiro Nishioka, Kazutoshi Komiya, Naoko Aragane, Shinya Kimura Department of Internal Medicine, Division of Hematology, Respiratory Medicine and Oncology, Faculty of Medicine, Saga University Background: Metastatic advanced gastric cancer(AGC) is predominantly a disease in JAPAN. A Phase II trial show the efficacy and safety of nab-paclitaxel plus ramucirumab combination therapy for previously treated advanced gastric cancer but the benefits of second-line chemotherapy in real world including elderly patients remain uncertain. Methods: We retrospectively examined pts with AGC who were treated in Saga-university hospital. The key inclusion criteria were ECOG PS 0-2 and refractory/intolerant to first line treatments. The objective was the efficacy of Ramucirumab plus nab-Paclitaxel as second-line therapy in real-world patients with AGC. Results: A total of 14 patients underwent second-line chemotherapy for gastric cancer between 2017 and 2018 at our hospital. We evaluated the outcome in terms of median progressive free survival (PFS) and overall survival (OS) respectively. The ORR assessed was 40.0% and the DCR was 100%. The median PFS was 7.6 months (95% CI 2.1-17.5). The median OS was not reached at the data cutoff. The main treatment-related over grade 2 adverse events were decreased neutrophil count (60%),hypertension (26%) and proteinuria (0%). Conclusions: Nab-paclitaxel plus ramucirumab combination therapy shows similar treatment results to the Phase II study and toxicities were safety manageable. This treatment regimen could be a useful second line treatment option for patients with previously treated AGC.
P3 030
C-reactive protein predicts recurrence after postoperative chemotherapy using S-1 in advanced gastric cancer patients
Takayuki Shimizu, Mitsuru Ishizuka, Takao Arakawa, Takashi Suzuki, Kazuma Tago, Hiroyuki Hachiya, Yasuhiro Harada, Kyunghwa Park, Takayuki Shiraki, Yuhki Sakuraoka, Shozo Mori, Akihito Abe, Yukihiro Iso, Kazutoshi Takagi, Taku Aoki, Keiichi Kubota Second Department of Surgery, Dokkyo Medical University Background&Aim: According to the Japanese gastric cancer treatment guidelines, postoperative adjuvant chemotherapy (PAC) using S-1 is recommended for patients undergoing curative surgery for advanced gastric cancer (GC). Recently, new chemotherapeutic regimens such as S-1 plus oxaliplatin and capecitabine plus oxaliplatin were reported to be applicable and safe as new PAC for stage II and III of GC patients. Although the option of PAC has been increased, it is still unclear how to choose the best regimen of PAC for advanced GC patients. Therefore, we aimed to investigate the clinical characteristics which are closely associated with the recurrence of GC in patients with PAC using S-1. Methods: Thirty-nine patients who received PAC using S-1 more than 1 year after curative surgery for advanced GC from March 2005 to December 2017 were enrolled. Univariate and multivariate analyses using the Cox proportional hazard model were performed to detect clinical characteristics that correlated with recurrence, and their cut-off values were identified using receiver operating characteristic (ROC) curve analyses to divide patients into two groups such as recurrence and non-recurrence group. Kaplan-Meier analysis and log-rank test were used for comparison of relapse-free survival (RFS). Results: Sixteen patients had recurrence after surgery (41%, 16/39). Multivariate analysis using clinical characteristics selected by univariate analyses revealed that C-reactive protein (>0.3/0.3, mg/dL) (hazard ratio [HR], 10.73; 95% CI, 1.824-63.14; P ¼ 0.009) was significantly associated with recurrence. Kaplan-Meier analysis and logrank test demonstrated that C-reactive protein (>0.3/0.3, mg/dL) was also significantly associated with RFS (P < 0.001).
vi140 | Poster Session
Conclusion: C-reactive protein is significantly associated with recurrence of GC in patients with PAC using S-1 after curative surgery.
P3 036
The clinicopathological features of long-term survivors of metastatic gastric cancer
Kenji Ina1, Ryuichi Furuta1, Megumi Kabeya2, Satoshi Hibi2, Shu Yuasa2, Yuko Kato3, Takashi Yoshida4, Takae Kataoka4, Satoshi Kayukawa4 1 Department of Medical Oncology, Nagoya Memorial Hospital, 2Department of Hospital Pharmacy, Nagoya Memorial Hospital, 3Medical Social Work Consultation Room, Nagoya Memorial Hospital, 4Department of Clinical Oncology, Nagoya Memorial Hospital Background: Metastatic gastric cancer has a poor prognosis. Overall survival in these patients is approximately 1 years, despite the development of chemotherapeutic and biological agents. The incidence of long-term survivors of metastatic gastric cancer beyond 5 years after the initiation of chemotherapy has been reported to be less than 10%. Methods: The characteristics of long-term survivors were compared with those of poor responders to determine the specific factors that regulate chemosensitivity. Those who died within six months after the initiation of chemotherapy were considered as poor responders in this analysis. Medical records were retrospectively reviewed to determine the clinicopathological features of metastatic gastric cancer patients receiving chemotherapy in Nagoya Memorial Hospital. Statistical analyses were carried out by Fisher’s exact test and then a multivariate analysis. Differences with P values less than 0.05 were considered statistically significant. The chart review was approved by ethics committee of Nagoya Memorial Hospital. Results: We experienced 8 long-term survivors and 12 poor responders. The analysis showed that number of metastatic sites might be different between 2 groups (P ¼ 0.0144). The objective response rates of long-term survivors and poor responders were 62.5% (CR 4, PR 1) and 0%, respectively. Conclusions: We found that tumor burden might be associated with the prognosis of affected patients. Good response to systemic chemotherapy should be essential for prolonged survival of patients with distant metastases.
P3 057
Treatment Outcomes after Pulmonary Stereotactic Body Radiotherapy for Oligometastatic or Oligorecurrent Lung Lesions
Brendan Sh Chia Radiation Oncology Department, National Cancer Centre Singapore, Singapore Objective: Using ablative techniques like stereotactic body radiation therapy (SBRT) in patients with limited metastases may improve survival outcomes in select groups of patients. We review the outcomes of patients treated with oligometastatic/recurrent lung lesions in our centre and analyse variables that might have affected them. Methods: A retrospective review of patients treated from Jan 2010 to Dec 2016 was conducted. The data was analysed using SPSS ver23. Results: A total of 46 patients with 51 lung lesions were treated with SBRT. Majority of lesions were of lung and colorectal cancers. Histological confirmation was obtained in 50%. Median SBRT biological effective dose (BED) was 105.6Gy and median follow-up was 26.9 months. There were 12 (22.6%) local failures at last follow-up. Median progression free survival (PFS) was 13.7 months (95% CI: 3.9 -23.5 months). Median overall survival (OS) was 42.2 months (95% CI: 30.8 - 53.5 months). The 2 year PFS and OS was 32.6% and 81.9% respectively. There were 3 (6.5%) likely radiotherapy related grade 3-4 pulmonary toxicities. On univariate analysis, local control rates were better with a higher BED and in squamous cell histology. Progression free survival was better for patients with metachronous lesions, higher BED, controlled primary lesions and when treatment to all visible lesions was given. Only patients with solitary metastatic lesions had better OS (44.7 months) and PFS (21.9 months) on univariate analysis. Local failure and progression predicted for worst OS. Conclusion: The patients in this study are heterogeneous. Survival outcomes were better in patients with solitary metastatic lesions. This may be due to selection of patients with indolent disease biology. Better PFS were seen with higher BED and when all visible lesions were ablated. Further studies are needed.
P3 061
Comparative study on safety after primary and secondary treatment in EGFR positive NSCLC administered Osimertinib
Kengo Umehara1, Keisuke Gto1, Yuki Okayama1, Shiori Noomote1, Takayuki Toda1, Yasuka Okazaki1, Azusa Wakamoto1, Tae Hatsuyama1, Osamu Honjo2, Hideki Sato3 1 Sapporo minami sanjo hospital pharmaceutical department, 2Sapporo minami sanjo hospital respiratory medicine department, 3Hokkaido university of science pharmacy department of pharmacy department of clinical pharmacology major Background: Since osimertinib significantly prolonged progression free survival compared with conventional EGFR-TKI and was well-tolerated, it was approved in August
Volume 30 | Supplement 6 | October 2019
Downloaded from https://academic.oup.com/annonc/article-abstract/30/Supplement_6/mdz343.102/5583023 by University of Cambridge user on 27 December 2019
Methods: We have retrospectively reviewed data of all patients in metastatic gastric cancer who received chemotherapy in our hospital and investigated the efficacy and adverse events of chemotherapy after progression on nivolumab. Results: Between September 2017 and January 2019, 29 patients received nivolumab for metastatic gastric cancer. 11 patients received subsequent treatment following nivolumab. The median age was 70. Performance status (0/1/2); 2/8/1. Previous treatment regimens (2/3/4/5); 4/3/2/1. Chemotherapy regimen (irinotecan / nab-paclitaxel6ramcirumab / CAPOX6trastuzumab / SOXþtrastuzumab); 3/5/2/1. Overall Response rate was 27%. 2 patients for nab-PTXþramcirumab and 1patient of CAPOXþtrastuzumab had a PR, 1patient for nab-PTXþramcirumab had a SD, 5 patients had a PD and 1 patient had a NE. Median PFS was 3.3 (95% CI. 0.8-5.5) months. Median OS was 8.0 (95%CI. 2.3-11.6) months. One patient developed Gr3 dysfunction of liver maybe due to nivolumab. Other adverse events were mild. Conclusions: We evaluated the efficacy of chemotherapy after progression on nivolumab. Further investigation is warranted to reveal an immunotherapy-induced chemosensitization effect.
Annals of Oncology
Annals of Oncology
P2 308
Successful treatment with osimertinib for leptomeningeal carcinomatosis from NSCLC with the EGFR T790M mutation
Naruo Yoshimura, Hidenori Takahashi, Emiko Kurosawa, Akiko Tanaka, Masahito Ebina, Takashi Ohrui Department of Pulmonology, Tohoku Medical And Pharmaceutical University Osimertinib is a third-generation tyrosine kinase inhibitor (TKI) of the epidermal growth factor receptor (EGFR) that has been approved for the treatment of metastatic non-small cell lung cancer (NSCLC) with EGFR mutation, and positive for the secondary T790M mutation of EGFR. In a preclinical study, it also showed efficacy against leptomeningeal carcinomatosis (LMC) derived from NSCLC resistant to first-generation and second-generation EGFR-TKIs. We report the case of a patient aged 55 years with symptomatic LMC derived from NSCLC. We detected T790M mutation of EGFR by liquid biopsy with blood sample. He showed a clinical and radiographic response to osimertinib.
P3 014
Maung Kyaw Maung Radiation Oncology Department, Yangon General Hospital, Yangon, Myanmar Background: Due to loco-regionally advanced at diagnosis, multi-modality treatment become optional for most of oesophageal cancer patients. With advanced imaging modalities and treatment machines, conformal radiotherapy with concurrent chemotherapy is the standard approach for non-surgical candidates. The aim of the present study was to assess immediate loco-regional response of neoadjuvant chemotherapy followed by concurrent chemoradiation therapy for oesophageal cancer patients. Methods: This study include histologically proven oesophageal cancer patients who are refuse or unfit for surgery or unresectable disease with performance status 0-2. Neoadjuvant chemotherapy 2 cycles with cisplatin and 5FU regime followed by concurrent chemoradiation therapy (3D CRT, 50 Gy over 5 weeks with single agent cisplatin 75 mg/m2 on day 1 and 21 of radiotherapy was given. Response assessment was done with CT scan and endoscopy at 6th week after RT. Written informed consent was obtained from all patients. Results: 26 patients were included in the study between August 2015 and December 2016. Commonest age group was within 5th to 7th decade of life. 16 were male (61.5%). 25 had SCCs (96.2%). 18 patient were with oesophageal cancer at middle third (69.3%). 15 present with grade III dysphagia (57.7%). 18 patients were stage III at the time of diagnosis. Total treatment compliance was 69.2%. During treatment, dysphagia grade revealed stable during first three weeks and worsened slightly over the last 2 weeks. During follow up period, 16 patients (61.5%) became free from dysphagia at 4th week and 19 patients (73.1%) at 6th weeks. On response assessment by CT and OGDS at 6th week, complete response was 15 (57.7%) and 18(69.3%) respectively and so overall response rate was 57.7%. Conclusion: This results support the feasibility of neoadjuvant chemotherapy followed by concurrent 3D CRT for oesophageal cancer patients with potential for a cure effect with acceptable toxicities.
P3 015 P2 310
Two cases of congestive heart failure during osimertinib treatment for EGFR mutant NSCLC
Satoshi Hara Respiratory Division, Department of Internal Medicine, Itami City Hospital We herein report two case of fatal congestive heart failure during osimertinib treatment for epidermal growth factor receptor (EGFR) mutant non-small cell lung cancer (NSCLC). Case1: A 66-year-old woman presented with progressive palpitation and dyspnea two months after starting osimertinib for the treatment of EGFR T790M-positive NSCLC. An echocardiogram demonstrated severe decreased left ventricular systolic function. She was diagnosed with fatal congestive heart failure caused by osimertinib treatment. Her general condition deteriorated, and she died three months after starting osimertinib. Case2: A 84-year-old woman was treated for recurrent EGFR mutant NSCLC after lobectomy, and osimertinib was administered. Severe exertional dyspnea appeared one month after starting osimertinib. She was also diagnosed with fatal congestive heart failure caused by osimertinib, and died for a few days. The causal relationship between osimertinib and cardiotoxicity has so far received little attention and thus remains unclear. Osimertinib inhibits HER2 (ERBB2) in addition to EGFR (ERBB1), thereby potentially causing cardiotoxicity.
P2 313
Clinical effect of alectinib in patients with ALK-positive non-small cell lung cancer
Koichi Nishi Department of Respiratory Medicine, Ishikwa Prefectural Central Hospital The clinical effect of alectinib (ALC) in patiets with ALK-positive non-small cell lung cancer was examined. The subjects were 8 ALK-positive non-small cell lung cancers who received ALC during the period from July 2014 to December 2018. The median age was 61.5 years old and all cases were adenocarcinomas. There were 5 cases of primary treatment administration, 2 cases of secondary treatment administration, 1 case of tertiary treatment administration. Response rate was 2 complete response (25.0%), partial response 3 cases (37.5%), disease stabilization 3 cases (37.5%), disease progress 0 cases (0%). Median progression-free survival after ALC administration was 212 days, median overall survival was 510 days, and good therapeutic effect was obtained. Also, no serious adverse events were observed.
Neoadjuvant Chemotherapy Followed by Concurrent Chemoradiation Therapy for Oesophageal Cancer Patients
Assessing the impact of sequence in delivering primary-directed palliative radiotherapy in esophageal cancer
Shaun Zhirui Ho, Yen Sin Koh, Michael Wang, Faye Lim, Francis Chin, Connie Yip, Tianrui Siow, Fuqiang Wang Division of Radiation Oncology, National Cancer Center Singapore, Singapore Background: The optimal sequence for primary-directed palliative radiotherapy in esophageal cancer is unknown. As the survival outcomes of these patients are poor, it is important to balance survival benefits from systemic chemotherapy against the benefits of primary-directed radiotherapy. Methods: We have retrospectively reviewed esophageal cancer patients who received palliative radiotherapy to the primary lesion and grouped them according to the sequence of treatment: chemotherapy followed by radiotherapy (C-RT), radiotherapy followed by chemotherapy (RT-C), or radiotherapy alone (RTa). We are interested in overall survival and the time spent on radiotherapy as a percentage of the time between start of radiotherapy to death (T-SPORT). Results: 92 patients receiving primary-directed radiotherapy were included in the study. Median overall survival in the C-RT and RT-C groups were 1.14 (0.82-1.72) and 0.95 (0.56-1.36) months respectively, which were significantly longer than the RTa group of 0.50 (0.38-0.74). On multivariate analysis, the groups receiving chemotherapy have similar hazard ratios when compared to RT alone (C-RT: HR 0.50 (0.30-0.84), p ¼ 0.008; RT-C: 0.51 (0.28 - 0.93), p ¼ 0.03). Median T-SPORT was 10.04% in C-RT group, similar to RTa group of 12.39%, whilst the RT-C group had the lowest value of 4.47%. Conclusion: We demonstrate that systemic chemotherapy has survival benefit regardless of sequence in the palliative management of esophageal cancer. Patients having primary-directed palliative radiotherapy before chemotherapy do not have worse overall survival. By having radiotherapy early, these patients spend a lower portion of remaining lifespan receiving radiotherapy, with subsequent more time to experience the benefits of treatment.
P3 027
Efficacy of chemotherapy following nivolumab in metastatic gastric cancer
Kohei Akiyoshi, Yuki Nakatani, Yuko Tsuboguchi, Yumi Yoshii, Shinya Ueda, Shunsuke Okazaki, Shinya Tokunaga, Haruko Daga Department of Medical Oncology, Osaka City General Hospital Background: Immuno-checkpoint inhibitors, nivolumab targeting programmed cell death 1 (PD-1) can result in significant benefit to gastric cancer. Some recent data about non-small cell lung cancer suggest anti-PD-1 therapy may enhance sensitivity to subsequent chemotherapy. To date, there are no reports on treatment efficacy after failure of PD-1 blockade in advanced gastric cancer. Therefore, we aimed to report the efficacy of chemotherapy after progressive disease on nivolumab.
Volume 30 | Supplement 6 | October 2019
doi:10.1093/annonc/mdz343 | vi139
Downloaded from https://academic.oup.com/annonc/article-abstract/30/Supplement_6/mdz343.102/5583023 by University of Cambridge user on 27 December 2019
Case 2: 72 y.o female contracted multiple lymphnode metastases and peritoneal dissemination of sigmoid colon cancer. She was treated by the following chemotherapies [FOLFOXþCET, FOLFIRIþBEV] and ALF was introduced in 3rd line. 3 courses of FOLFIRIþAFL were performed but the tumors were increased (PD). Case 3: 67 y.o female contracted unresectable rectal cancer and multiple lymphnode metastases. She was treated by the following chemotherapies [CAPOXþBEV, FOLFIRIþRAM] and ALF was introduced in 3rd line. 1 course of FOLFIRIþAFL was performed, but she deteriorated into bad condition and this therapy was stopped. Case 4: 64 y.o female contracted paraaortic lymphnode metastases of rectal cancer . He was treated by the following chemotherapies [FOLFOXþCET, FOLFIRIþBEV, FOLFIRIþPANI] and ALF was introduced in 4th line. 3 courses of FOLFIRIþAFL were performed but the tumors were increased (PD). Conclusion: Only Case1 showed tumor regression. But the other 3 cases those were treated by FOLFIRI þ molecularly targeted agents except AFL in previous line, showed no efficacy. It is suggested that only exchange of molecularly targeted agents to AFL in FOLFIRI therapy dose not show the enough antitumor effect in colorectal cancer.
abstracts
P3 029
Nab-paclitaxel plus ramucirumab combination therapy as secondline with advanced gastric cancer:Retrospective study
Tomomi Kashiwada, Atsujiro Nishioka, Kazutoshi Komiya, Naoko Aragane, Shinya Kimura Department of Internal Medicine, Division of Hematology, Respiratory Medicine and Oncology, Faculty of Medicine, Saga University Background: Metastatic advanced gastric cancer(AGC) is predominantly a disease in JAPAN. A Phase II trial show the efficacy and safety of nab-paclitaxel plus ramucirumab combination therapy for previously treated advanced gastric cancer but the benefits of second-line chemotherapy in real world including elderly patients remain uncertain. Methods: We retrospectively examined pts with AGC who were treated in Saga-university hospital. The key inclusion criteria were ECOG PS 0-2 and refractory/intolerant to first line treatments. The objective was the efficacy of Ramucirumab plus nab-Paclitaxel as second-line therapy in real-world patients with AGC. Results: A total of 14 patients underwent second-line chemotherapy for gastric cancer between 2017 and 2018 at our hospital. We evaluated the outcome in terms of median progressive free survival (PFS) and overall survival (OS) respectively. The ORR assessed was 40.0% and the DCR was 100%. The median PFS was 7.6 months (95% CI 2.1-17.5). The median OS was not reached at the data cutoff. The main treatment-related over grade 2 adverse events were decreased neutrophil count (60%),hypertension (26%) and proteinuria (0%). Conclusions: Nab-paclitaxel plus ramucirumab combination therapy shows similar treatment results to the Phase II study and toxicities were safety manageable. This treatment regimen could be a useful second line treatment option for patients with previously treated AGC.
P3 030
C-reactive protein predicts recurrence after postoperative chemotherapy using S-1 in advanced gastric cancer patients
Takayuki Shimizu, Mitsuru Ishizuka, Takao Arakawa, Takashi Suzuki, Kazuma Tago, Hiroyuki Hachiya, Yasuhiro Harada, Kyunghwa Park, Takayuki Shiraki, Yuhki Sakuraoka, Shozo Mori, Akihito Abe, Yukihiro Iso, Kazutoshi Takagi, Taku Aoki, Keiichi Kubota Second Department of Surgery, Dokkyo Medical University Background&Aim: According to the Japanese gastric cancer treatment guidelines, postoperative adjuvant chemotherapy (PAC) using S-1 is recommended for patients undergoing curative surgery for advanced gastric cancer (GC). Recently, new chemotherapeutic regimens such as S-1 plus oxaliplatin and capecitabine plus oxaliplatin were reported to be applicable and safe as new PAC for stage II and III of GC patients. Although the option of PAC has been increased, it is still unclear how to choose the best regimen of PAC for advanced GC patients. Therefore, we aimed to investigate the clinical characteristics which are closely associated with the recurrence of GC in patients with PAC using S-1. Methods: Thirty-nine patients who received PAC using S-1 more than 1 year after curative surgery for advanced GC from March 2005 to December 2017 were enrolled. Univariate and multivariate analyses using the Cox proportional hazard model were performed to detect clinical characteristics that correlated with recurrence, and their cut-off values were identified using receiver operating characteristic (ROC) curve analyses to divide patients into two groups such as recurrence and non-recurrence group. Kaplan-Meier analysis and log-rank test were used for comparison of relapse-free survival (RFS). Results: Sixteen patients had recurrence after surgery (41%, 16/39). Multivariate analysis using clinical characteristics selected by univariate analyses revealed that C-reactive protein (>0.3/0.3, mg/dL) (hazard ratio [HR], 10.73; 95% CI, 1.824-63.14; P ¼ 0.009) was significantly associated with recurrence. Kaplan-Meier analysis and logrank test demonstrated that C-reactive protein (>0.3/0.3, mg/dL) was also significantly associated with RFS (P < 0.001).
vi140 | Poster Session
Conclusion: C-reactive protein is significantly associated with recurrence of GC in patients with PAC using S-1 after curative surgery.
P3 036
The clinicopathological features of long-term survivors of metastatic gastric cancer
Kenji Ina1, Ryuichi Furuta1, Megumi Kabeya2, Satoshi Hibi2, Shu Yuasa2, Yuko Kato3, Takashi Yoshida4, Takae Kataoka4, Satoshi Kayukawa4 1 Department of Medical Oncology, Nagoya Memorial Hospital, 2Department of Hospital Pharmacy, Nagoya Memorial Hospital, 3Medical Social Work Consultation Room, Nagoya Memorial Hospital, 4Department of Clinical Oncology, Nagoya Memorial Hospital Background: Metastatic gastric cancer has a poor prognosis. Overall survival in these patients is approximately 1 years, despite the development of chemotherapeutic and biological agents. The incidence of long-term survivors of metastatic gastric cancer beyond 5 years after the initiation of chemotherapy has been reported to be less than 10%. Methods: The characteristics of long-term survivors were compared with those of poor responders to determine the specific factors that regulate chemosensitivity. Those who died within six months after the initiation of chemotherapy were considered as poor responders in this analysis. Medical records were retrospectively reviewed to determine the clinicopathological features of metastatic gastric cancer patients receiving chemotherapy in Nagoya Memorial Hospital. Statistical analyses were carried out by Fisher’s exact test and then a multivariate analysis. Differences with P values less than 0.05 were considered statistically significant. The chart review was approved by ethics committee of Nagoya Memorial Hospital. Results: We experienced 8 long-term survivors and 12 poor responders. The analysis showed that number of metastatic sites might be different between 2 groups (P ¼ 0.0144). The objective response rates of long-term survivors and poor responders were 62.5% (CR 4, PR 1) and 0%, respectively. Conclusions: We found that tumor burden might be associated with the prognosis of affected patients. Good response to systemic chemotherapy should be essential for prolonged survival of patients with distant metastases.
P3 057
Treatment Outcomes after Pulmonary Stereotactic Body Radiotherapy for Oligometastatic or Oligorecurrent Lung Lesions
Brendan Sh Chia Radiation Oncology Department, National Cancer Centre Singapore, Singapore Objective: Using ablative techniques like stereotactic body radiation therapy (SBRT) in patients with limited metastases may improve survival outcomes in select groups of patients. We review the outcomes of patients treated with oligometastatic/recurrent lung lesions in our centre and analyse variables that might have affected them. Methods: A retrospective review of patients treated from Jan 2010 to Dec 2016 was conducted. The data was analysed using SPSS ver23. Results: A total of 46 patients with 51 lung lesions were treated with SBRT. Majority of lesions were of lung and colorectal cancers. Histological confirmation was obtained in 50%. Median SBRT biological effective dose (BED) was 105.6Gy and median follow-up was 26.9 months. There were 12 (22.6%) local failures at last follow-up. Median progression free survival (PFS) was 13.7 months (95% CI: 3.9 -23.5 months). Median overall survival (OS) was 42.2 months (95% CI: 30.8 - 53.5 months). The 2 year PFS and OS was 32.6% and 81.9% respectively. There were 3 (6.5%) likely radiotherapy related grade 3-4 pulmonary toxicities. On univariate analysis, local control rates were better with a higher BED and in squamous cell histology. Progression free survival was better for patients with metachronous lesions, higher BED, controlled primary lesions and when treatment to all visible lesions was given. Only patients with solitary metastatic lesions had better OS (44.7 months) and PFS (21.9 months) on univariate analysis. Local failure and progression predicted for worst OS. Conclusion: The patients in this study are heterogeneous. Survival outcomes were better in patients with solitary metastatic lesions. This may be due to selection of patients with indolent disease biology. Better PFS were seen with higher BED and when all visible lesions were ablated. Further studies are needed.
P3 061
Comparative study on safety after primary and secondary treatment in EGFR positive NSCLC administered Osimertinib
Kengo Umehara1, Keisuke Gto1, Yuki Okayama1, Shiori Noomote1, Takayuki Toda1, Yasuka Okazaki1, Azusa Wakamoto1, Tae Hatsuyama1, Osamu Honjo2, Hideki Sato3 1 Sapporo minami sanjo hospital pharmaceutical department, 2Sapporo minami sanjo hospital respiratory medicine department, 3Hokkaido university of science pharmacy department of pharmacy department of clinical pharmacology major Background: Since osimertinib significantly prolonged progression free survival compared with conventional EGFR-TKI and was well-tolerated, it was approved in August
Volume 30 | Supplement 6 | October 2019
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Methods: We have retrospectively reviewed data of all patients in metastatic gastric cancer who received chemotherapy in our hospital and investigated the efficacy and adverse events of chemotherapy after progression on nivolumab. Results: Between September 2017 and January 2019, 29 patients received nivolumab for metastatic gastric cancer. 11 patients received subsequent treatment following nivolumab. The median age was 70. Performance status (0/1/2); 2/8/1. Previous treatment regimens (2/3/4/5); 4/3/2/1. Chemotherapy regimen (irinotecan / nab-paclitaxel6ramcirumab / CAPOX6trastuzumab / SOXþtrastuzumab); 3/5/2/1. Overall Response rate was 27%. 2 patients for nab-PTXþramcirumab and 1patient of CAPOXþtrastuzumab had a PR, 1patient for nab-PTXþramcirumab had a SD, 5 patients had a PD and 1 patient had a NE. Median PFS was 3.3 (95% CI. 0.8-5.5) months. Median OS was 8.0 (95%CI. 2.3-11.6) months. One patient developed Gr3 dysfunction of liver maybe due to nivolumab. Other adverse events were mild. Conclusions: We evaluated the efficacy of chemotherapy after progression on nivolumab. Further investigation is warranted to reveal an immunotherapy-induced chemosensitization effect.
Annals of Oncology