- Email: [email protected]
Clinical response to subsequent chemotherapy after nivolumab in patients with advanced gastric cancer
abstracts
Annals of Oncology P1 012
Primary tumor location and benefit of anti-EGFRs as second or later line treatment in RAS-RAS wild type mCRC patients
Ayumi Saito, Misao Fukuda, Hiroya Ashimine, Yasutomo Miyaji, Sunngi Chi, Yu Oyama Medical Oncology Department, Kameda Medical Center
P1 020
Primary small bowel adenocarcinoma : a case report
Mari Sato, Yoshihiro Moriguti, Oushu Kashima, Takuya Masaki, Tatsuki Morosawa, Takahiro Oomori, Hiroyuki Funayama Department of Gastroenterology, Saka General Hospital A 69-year-old woman visited our outpatient clinic due to abdominal pain and anorexia. She received initial diagnostic workup, and was admitted to the hospital as an inpatient because of ileus. CT showed tumor with a diameter of 3cm in upper left abdomen, liver metastasis, peritoneal fluid localized in the pelvic cavity, and peritoneal node. Upper and lower gastrointestinal endoscopy showed no abnormalities, and percutaneous liver biopsy confirmed adenocarcinoma. PET showed a focal abnormal uptake in proximal jejunum, but no abnormalities in pancreas and biliary tract. We diagnosed the patient with small bowel cancer. It was considered unresectable, and FOLFOX chemotherapy was initiated. However, during FOLFOX chemotherapy after 1st course, CT showed that exacerbation of primary lesion and liver mass, and significant increase in ascites. She subsequently died of pneumonia day 32 after the start of chemotherapy. Autopsy findings revealed primary small bowel adenocarcinoma with proximal jejunum. Histological response was Grade1a. The incidence of small bowel adenocarcinoma (SBA) is very low, accounting for 0.1%0.3% of all gastrointestinal malignant neoplasms. Many cases have been reported to be within 50 cm of Treitz ligament or Bauhin valve. For diagnosis of SBA, some reports suggest small bowel series, gastrointestinal endoscope, CT, and PET are useful. However, in many advanced cases it is difficult to apply curative therapy at the time of discovery. There is no standard treatment especially for unresectable small bowel cancer, and the prognosis is poor. In this case SBA was confirmed by metastatic lesion biopsy and exclusion diagnosis. Because the disease was already advanced at the time of diagnosis and furthermore time was necessary for diagnostic workup, it caused deterioration of the general condition. As a result, adequate chemotherapy could not be performed. There is a need for further case studies to establish diagnosis and treatment of SBA.
P1 022
Clinical response to subsequent chemotherapy after nivolumab in patients with advanced gastric cancer
Kai Tsugaru1, Yasutaka Sukawa1, Keitaro Shimozaki1, Kazuhiro Togasaki1, Kenta Kawasaki1, Kenro Hirata1, Hideyuki Hayashi2, Yasuo Hamamoto2, Takanori Kanai1, Hiromasa Takaishi2 1 Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, 2Keio Cancer Center, Keio University School of Medicine Backgroud: Recent studies reported that anti-PD-1 antibody increases the sensitivity of subsequent chemotherapy in several types of cancer. However, there is no evidence for the efficacy of subsequent chemotherapy after nivolumab in patients with gastric cancer. Method: We retrospectively assessed clinical data of patients with metastatic or unresectable gastric cancer who were treated with nivolumab in Keio university hospital between September 2017 and January 2019. Tumor response and prognosis of
Volume 30 | Supplement 6 | October 2019
P1 024
Retrospective analysis for efficacy and safety of nivolumab in advanced gastric cancer patients with malignant ascites
Hirosumi Suzuki, Takeshi Yamada, Yuuya Hagiwara, Takafumi Ikeda, Yoshiki Komatsu, Yoshitaka Tange, Yutaro Sugiyama, Yoshiyuki Yamamoto, Toshikazu Moriwaki, Ichinosuke Hyodo Division of Gastroenterology, University of Tsukuba Hospital Background: Nivolumab is a standard of care as third line therapy for advanced gastric cancer. However, we have still few data about efficacy and safety of nivolumab for patients with malignant ascites. Methods: We conducted a single institute retrospective study to evaluate the efficacy and safety of nivolumab alone for advanced gastric cancer with malignant ascites. We reviewed medical records of patients who received nivolumab as later-line for advanced gastric cancer from October 2017 to February 2019. High ascites burden (HAB) was defined as moderate or massive ascites. Low ascites burden (LAB) was defined as none or a little amount of localized ascites only at pelvic and/or liver surface. The efficacy and safety data were compared between these two groups. Tumor responses were assessed with RECIST and/or change of ascites volume. Results: There were 13 patients with HAB and 17 patients with LAB treated with nivolumab. The HAB group was significantly younger (59 vs 65 years, p ¼ 0.03), and had less prior gastrectomy (31 vs 71%, p ¼ 0.04) and poorer performance status (PS 0; 8% vs 59%, p ¼ 0.01), compared to LAB. Disease control rate was 31% (4/13) in the HAB group and 24% (4/17) in the LAB group (p ¼ 0.70). The proportion of subsequent chemotherapy was similar to each group (10/13 vs 9/17, p ¼ 0.26). The median follow-up time was 12 months. The median PFS was 1.0 and 1.5 months (p ¼ 0.94) in the HAB and LAB groups, respectively. The median OS was 2.5 and 11.5 months (p ¼ 0.10) in the HAB and LAB groups, respectively. In the HAB group, 4 patients with stable disease or better response showed durable PFS of 2þ to 10þ months, and all survived at the analysis. Immune-related adverse events occurred in 31% of the HAB group and 12% of the LAB group (p ¼ 0.36), including one grade 3 event in each group. Conclusion: Nivolumab was effective in some patients with HAB as well as LAB, and also tolerable in patients with HAB.
P1 025
Nivolumab for poor performance status patients : retrospective analysis
Toshihiko Matsumoto, Shogo Kimura, Hitomi Himei, Ukyo Okazaki, Yusuke Kurioka, Takao Tsuduki, Shijiro Takagi, Masahiro Takatani, Takanori Watanabe, Hirofumi Morishita Himeji red cross hospital Objective: Nivolumab has changed the treatment of advanced gastric cancer (AGC). Nivolumab shows better outcome compared to best supportive care in AGC patients who received at least two prior regimen. Although there is not reliable date of poor performance status(PS) AGC patients who received nivolumab.We investigated efficacy and safety of nivolumab for AGC patients with poor PS. Methods: We retrospectively collected clinicopathologic data from patients with AGC who received nivolumab monotherapy in our institution from October 2017 to January 2019. Results: 37 AGC patients received nivolumab in Himeji Red Cross hospital from October 2017 to January 2019.We analyzed 17 patients who were PS over 1. 15 patients was male, median age was 64 (42-80), 10 patients was PS 2 and 7 patients PS 3, 11 patients were diffuse type, median number of metastatic organ was 2(range 1-5), 3 patients had liver metastasis, 13 patients had peritoneum dissemination and ascites.12 patients received 2 prior regimen, 5 patients received over 2 regimen. Median progression free survival was 29 days(95% CI: 21-65 days) and overall survival was 85 days(95% CI: 35-111 days), response rate was 6%, disease control rate was 19%, and 6 months survival rate was 12%. Immune-related adverse events(iRAEs) were observed 4 patients(24%), colitis was observed 2patients(12%), hypothyroidism was observed 2patients(12%), and liver dysfunction was observed 1 patient(6%). Severe iRAEs was only one patients(colitis).
doi:10.1093/annonc/mdz343 | vi119
Downloaded from https://academic.oup.com/annonc/article-abstract/30/Supplement_6/mdz343.006/5582901 by Goteborgs Universitet user on 13 November 2019
Background: Retrospective analysis of randomized control trials suggested that rightsided tumors derive less benefit from addition of anti-epidermal growth factor receptor antibodies(anti-EGFRs) to chemotherapy as first-line therapy . Furthermore, other retrospective studies suggest that anti-EGFRs as second or later line treatment also derive less benefit in right-sided tumors compared with left-sided tumors, although there is no definitive Conclusion. Patients and Methods: Patients with KRAS and RAS wild type mCRC who were treated with anti-EGFRs as second or later line treatment from 2008 to 2018 at Kameda Medical Center were included in the study. We retrospectively analyzed the difference in efficacy of anti-EGFRs according to the location of primary tumor. Results: Among 69 of patients, 49 and 20 had right- and left-sided tumors, respectively. Thirty-six patients treated with chemotherapy plus anti-EGFRs (treatment A), 33 patients treated with anti-EGFRs alone (treatment B). Median overall survival was 33 month in left-sided tumors versus 22 month in right-sided tumors.Overall response rate(ORR), disease control rate(DCR), and median progression free survival(PFS) were 22%, 29% and 4.0 months in left-sided tumor and 0%, 10% and 2.5 months in right-sided tumors, respectively.(p ¼ 0.017)Overall response rate(ORR), disease control rate(DCR), the and median progression free survival(PFS) were 9%, 40% and 4.0 months in left-sided tumor and 0%, 9% and 1 months in right-sided tumors, respectively.(p ¼ 0.017) Conclusion: Compared with left-sided tumors, right-sided tumors responded less to anti-EGFRs and had poor prognosis.
subsequent chemotherapy after nivolumab were evaluated. Tumor response was evaluated according to Response Evaluation Criteria for Solid Tumors ver 1.1. Result: Of 34 patients treated with nivolumab, 12 patients received subsequent chemotherapy after cessation of nivolumab (CapeOX n ¼ 6, irinotecan n ¼ 3, others n ¼ 3). Response rate and disease control rate were 25% and 42%, respectively. Median progression-free survival (PFS) and median overall survival were 2.5 months and 4.5 months, respectively. In all 3 patients achieved partial response by subsequent chemotherapy, nivolumab was administered as third-line therapy and continued over 9 months with stable disease. Durable response was observed in two patients treated with CapeOX and irinotecan (PFS 15.7 and 15.6 months, respectively). These two patients survive more than 2 years after cessation of nivolumab due to progressive disease. Conclusion: Although sample number was limited, higher response rate was observed in patients with subsequent chemotherapy after nivolumab compared to previous reports of salvage line chemotherapy without nivolumab. The mechanism and biomarker of hypersensitivity for subsequent chemotherapy should be elucidated.
Annals of Oncology P1 012
Primary tumor location and benefit of anti-EGFRs as second or later line treatment in RAS-RAS wild type mCRC patients
Ayumi Saito, Misao Fukuda, Hiroya Ashimine, Yasutomo Miyaji, Sunngi Chi, Yu Oyama Medical Oncology Department, Kameda Medical Center
P1 020
Primary small bowel adenocarcinoma : a case report
Mari Sato, Yoshihiro Moriguti, Oushu Kashima, Takuya Masaki, Tatsuki Morosawa, Takahiro Oomori, Hiroyuki Funayama Department of Gastroenterology, Saka General Hospital A 69-year-old woman visited our outpatient clinic due to abdominal pain and anorexia. She received initial diagnostic workup, and was admitted to the hospital as an inpatient because of ileus. CT showed tumor with a diameter of 3cm in upper left abdomen, liver metastasis, peritoneal fluid localized in the pelvic cavity, and peritoneal node. Upper and lower gastrointestinal endoscopy showed no abnormalities, and percutaneous liver biopsy confirmed adenocarcinoma. PET showed a focal abnormal uptake in proximal jejunum, but no abnormalities in pancreas and biliary tract. We diagnosed the patient with small bowel cancer. It was considered unresectable, and FOLFOX chemotherapy was initiated. However, during FOLFOX chemotherapy after 1st course, CT showed that exacerbation of primary lesion and liver mass, and significant increase in ascites. She subsequently died of pneumonia day 32 after the start of chemotherapy. Autopsy findings revealed primary small bowel adenocarcinoma with proximal jejunum. Histological response was Grade1a. The incidence of small bowel adenocarcinoma (SBA) is very low, accounting for 0.1%0.3% of all gastrointestinal malignant neoplasms. Many cases have been reported to be within 50 cm of Treitz ligament or Bauhin valve. For diagnosis of SBA, some reports suggest small bowel series, gastrointestinal endoscope, CT, and PET are useful. However, in many advanced cases it is difficult to apply curative therapy at the time of discovery. There is no standard treatment especially for unresectable small bowel cancer, and the prognosis is poor. In this case SBA was confirmed by metastatic lesion biopsy and exclusion diagnosis. Because the disease was already advanced at the time of diagnosis and furthermore time was necessary for diagnostic workup, it caused deterioration of the general condition. As a result, adequate chemotherapy could not be performed. There is a need for further case studies to establish diagnosis and treatment of SBA.
P1 022
Clinical response to subsequent chemotherapy after nivolumab in patients with advanced gastric cancer
Kai Tsugaru1, Yasutaka Sukawa1, Keitaro Shimozaki1, Kazuhiro Togasaki1, Kenta Kawasaki1, Kenro Hirata1, Hideyuki Hayashi2, Yasuo Hamamoto2, Takanori Kanai1, Hiromasa Takaishi2 1 Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, 2Keio Cancer Center, Keio University School of Medicine Backgroud: Recent studies reported that anti-PD-1 antibody increases the sensitivity of subsequent chemotherapy in several types of cancer. However, there is no evidence for the efficacy of subsequent chemotherapy after nivolumab in patients with gastric cancer. Method: We retrospectively assessed clinical data of patients with metastatic or unresectable gastric cancer who were treated with nivolumab in Keio university hospital between September 2017 and January 2019. Tumor response and prognosis of
Volume 30 | Supplement 6 | October 2019
P1 024
Retrospective analysis for efficacy and safety of nivolumab in advanced gastric cancer patients with malignant ascites
Hirosumi Suzuki, Takeshi Yamada, Yuuya Hagiwara, Takafumi Ikeda, Yoshiki Komatsu, Yoshitaka Tange, Yutaro Sugiyama, Yoshiyuki Yamamoto, Toshikazu Moriwaki, Ichinosuke Hyodo Division of Gastroenterology, University of Tsukuba Hospital Background: Nivolumab is a standard of care as third line therapy for advanced gastric cancer. However, we have still few data about efficacy and safety of nivolumab for patients with malignant ascites. Methods: We conducted a single institute retrospective study to evaluate the efficacy and safety of nivolumab alone for advanced gastric cancer with malignant ascites. We reviewed medical records of patients who received nivolumab as later-line for advanced gastric cancer from October 2017 to February 2019. High ascites burden (HAB) was defined as moderate or massive ascites. Low ascites burden (LAB) was defined as none or a little amount of localized ascites only at pelvic and/or liver surface. The efficacy and safety data were compared between these two groups. Tumor responses were assessed with RECIST and/or change of ascites volume. Results: There were 13 patients with HAB and 17 patients with LAB treated with nivolumab. The HAB group was significantly younger (59 vs 65 years, p ¼ 0.03), and had less prior gastrectomy (31 vs 71%, p ¼ 0.04) and poorer performance status (PS 0; 8% vs 59%, p ¼ 0.01), compared to LAB. Disease control rate was 31% (4/13) in the HAB group and 24% (4/17) in the LAB group (p ¼ 0.70). The proportion of subsequent chemotherapy was similar to each group (10/13 vs 9/17, p ¼ 0.26). The median follow-up time was 12 months. The median PFS was 1.0 and 1.5 months (p ¼ 0.94) in the HAB and LAB groups, respectively. The median OS was 2.5 and 11.5 months (p ¼ 0.10) in the HAB and LAB groups, respectively. In the HAB group, 4 patients with stable disease or better response showed durable PFS of 2þ to 10þ months, and all survived at the analysis. Immune-related adverse events occurred in 31% of the HAB group and 12% of the LAB group (p ¼ 0.36), including one grade 3 event in each group. Conclusion: Nivolumab was effective in some patients with HAB as well as LAB, and also tolerable in patients with HAB.
P1 025
Nivolumab for poor performance status patients : retrospective analysis
Toshihiko Matsumoto, Shogo Kimura, Hitomi Himei, Ukyo Okazaki, Yusuke Kurioka, Takao Tsuduki, Shijiro Takagi, Masahiro Takatani, Takanori Watanabe, Hirofumi Morishita Himeji red cross hospital Objective: Nivolumab has changed the treatment of advanced gastric cancer (AGC). Nivolumab shows better outcome compared to best supportive care in AGC patients who received at least two prior regimen. Although there is not reliable date of poor performance status(PS) AGC patients who received nivolumab.We investigated efficacy and safety of nivolumab for AGC patients with poor PS. Methods: We retrospectively collected clinicopathologic data from patients with AGC who received nivolumab monotherapy in our institution from October 2017 to January 2019. Results: 37 AGC patients received nivolumab in Himeji Red Cross hospital from October 2017 to January 2019.We analyzed 17 patients who were PS over 1. 15 patients was male, median age was 64 (42-80), 10 patients was PS 2 and 7 patients PS 3, 11 patients were diffuse type, median number of metastatic organ was 2(range 1-5), 3 patients had liver metastasis, 13 patients had peritoneum dissemination and ascites.12 patients received 2 prior regimen, 5 patients received over 2 regimen. Median progression free survival was 29 days(95% CI: 21-65 days) and overall survival was 85 days(95% CI: 35-111 days), response rate was 6%, disease control rate was 19%, and 6 months survival rate was 12%. Immune-related adverse events(iRAEs) were observed 4 patients(24%), colitis was observed 2patients(12%), hypothyroidism was observed 2patients(12%), and liver dysfunction was observed 1 patient(6%). Severe iRAEs was only one patients(colitis).
doi:10.1093/annonc/mdz343 | vi119
Downloaded from https://academic.oup.com/annonc/article-abstract/30/Supplement_6/mdz343.006/5582901 by Goteborgs Universitet user on 13 November 2019
Background: Retrospective analysis of randomized control trials suggested that rightsided tumors derive less benefit from addition of anti-epidermal growth factor receptor antibodies(anti-EGFRs) to chemotherapy as first-line therapy . Furthermore, other retrospective studies suggest that anti-EGFRs as second or later line treatment also derive less benefit in right-sided tumors compared with left-sided tumors, although there is no definitive Conclusion. Patients and Methods: Patients with KRAS and RAS wild type mCRC who were treated with anti-EGFRs as second or later line treatment from 2008 to 2018 at Kameda Medical Center were included in the study. We retrospectively analyzed the difference in efficacy of anti-EGFRs according to the location of primary tumor. Results: Among 69 of patients, 49 and 20 had right- and left-sided tumors, respectively. Thirty-six patients treated with chemotherapy plus anti-EGFRs (treatment A), 33 patients treated with anti-EGFRs alone (treatment B). Median overall survival was 33 month in left-sided tumors versus 22 month in right-sided tumors.
subsequent chemotherapy after nivolumab were evaluated. Tumor response was evaluated according to Response Evaluation Criteria for Solid Tumors ver 1.1. Result: Of 34 patients treated with nivolumab, 12 patients received subsequent chemotherapy after cessation of nivolumab (CapeOX n ¼ 6, irinotecan n ¼ 3, others n ¼ 3). Response rate and disease control rate were 25% and 42%, respectively. Median progression-free survival (PFS) and median overall survival were 2.5 months and 4.5 months, respectively. In all 3 patients achieved partial response by subsequent chemotherapy, nivolumab was administered as third-line therapy and continued over 9 months with stable disease. Durable response was observed in two patients treated with CapeOX and irinotecan (PFS 15.7 and 15.6 months, respectively). These two patients survive more than 2 years after cessation of nivolumab due to progressive disease. Conclusion: Although sample number was limited, higher response rate was observed in patients with subsequent chemotherapy after nivolumab compared to previous reports of salvage line chemotherapy without nivolumab. The mechanism and biomarker of hypersensitivity for subsequent chemotherapy should be elucidated.