- Email: [email protected]
A multicenter retrospective study of Paclitaxel vs. Paclitaxel plus Ramucirumab for advanced gastric cancer patients
abstracts
Annals of Oncology hyperthyroidism (5.9% vs 0%) and pneumonitis (2.9% vs 0%) in ATZþnPTX and PlaþnPTX, respectively. The incidence of AESI was similar to that of overall study population. Conclusion: The efficacy and safety of ATZþnPTX as first line therapy in Japanese pts with TNBC were consistent with those of overall study population.
O1 9 4
A prospective real-world study of eribulin for HER2-negative recurrent breast cancer patients: final results
[Background]: Two global phase 3 trials (301 trial of first- or second-line eribulin, EMBRACE of third- or later-line eribulin) were carried out during development of eribulin for breast cancer treatment. In this post marketing observation study in Japan, efficacy and safety of eribulin in metastatic breast cancer patients were examined. Additionally, the results were compared with that of phase 3 trials. [Method]: We conducted a prospective study in patients with inoperable or recurrent HER2-negative breast cancer. We enrolled a similar number of patients receiving eribulin as first- or second-line therapy (early line) and those receiving eribulin as third- or later line therapy (later line), and followed the patients for two years (ClinicalTrials.gov Number: NCT02371174). For the overall survival and time to treatment failure, the estimated value of them were calculated by the Kaplan Meier method. The severity of adverse drug events was determined by CTCAE v 4.0. [Results]: During September 2014 to February 2016, 651cases were registered at 182 facilities. In analysis set, 637 patients (319 patients of early line/317 patients of late line/ 1 patient of unknown) was median age of 62.7 (30 - 85) years. Performance status 0/1/ 2/3/4 was seen in 360/234/38/5/0 patients, respectively. Dose reduction were required in 33% of patients. The median overall survival (early line/late line) was 18.8 months/ 12.6 months, respectively, and median time to treatment failure was 4.4 months/3.8 months, respectively. Major side effects (early line/late line) were neutropenia (51%/ 56%), leucopenia (55%/57%), peripheral neuropathy (32%/22%). Grade 3 peripheral neuropathy was 2%. [Conclusion]: The results of overall survival (18.8 months in early line, 12.6 months in later line) in this study is comparable to those of large phase 3 study (15.9 months in 301 trial, 13.1 months in EMBRACE). The incidence of Grade 3 peripheral neuropathy was lower than that of phase 3 trials.
O2 1 1
Pembrolizumab (pembro) in Mismatch Repair-Deficient (dMMR) Advanced Colorectal Cancer (CRC): KEYNOTE-164 Japan Subgroup
Hiroya Taniguchi1, Hiroki Hara2, Takayuki Yoshino1, Kiwamu Akagi3, Kohei Shitara1, Toshiki Masuishi4, Yasutoshi Kuboki1, Takashi Shimamoto5, Kenichi Ueki5, Shi Rong Han5, Kazuo Noguchi5, Luis A. Diaz6 1 Gastroenterology and Gastrointestinal Oncology, National Cancer Center Hospital East, Japan, 2Department of Gastroenterology, Saitama Cancer Center, 3Department of Molecular Diagnosis & Cancer Prevention, Saitama Cancer Center, 4Department of Clinical Oncology, Aichi Cancer Center Hospital, 5Oncology Science Unit, MSD K.K, 6 Department of Translational Medicine, Sidney Kimmel Cancer Center at Johns Hopkins University Background: Pembro is approved for microsatellite instability-high (MSI-H)/dMMR CRC that has progressed on fluoropyrimidineþoxaliplatinþirinotecan (FpþOxþIr), based in part on data from the ongoing phase 2 KEYNOTE-164 study (NCT02460198). The outcomes of the Japan (Jpn) subgroup of patients (pts) with dMMR CRC are reported. Methods: Pts with metastatic MSI-H/dMMR CRC with 2 lines of standard therapy (FpþOxþIr 6 anti-VEGF or anti-EGFR; cohort A) or 1 prior line of therapy (cohort B) received pembro 200 mg every 3 weeks for 2 years or until progression or unacceptable toxicity. Response was assessed every 9 weeks per RECIST v1.1. Primary end point was objective response rate (ORR); secondary end points were duration of response (DOR), disease control rate, progression-free survival (PFS), overall survival (OS), and safety. Data cutoff was February 10, 2017 (cohort A) and September 12, 2017 (cohort B). Results: Of the 124 enrolled pts, the Jpn subgroup comprised 7/61 pts in cohort A (cohort AJpn) and 6/63 pts in cohort B (cohort BJpn). At data cutoff, median followup was 13.2 months/13.2 months for cohorts A/AJpn and 12.6 months/13.6 months for cohorts B/BJpn. ORRs were 28% (95% CI, 20-44; 17 partial responses [PRs]) and 29% (95% CI, 4-71; 2 PRs) for cohorts A and AJpn, respectively, and 32% (95% CI, 21-45; 2 complete responses and 18 PRs) and 67% (95% CI, 22-96; 4 PRs) for cohorts B and BJpn, respectively. Median DOR was not reached for any group. 12-month PFS rates were 34%/29% for cohorts A/AJpn and 41%/67% for cohorts B/BJpn. 12-month OS rates were 72%/57% and 76%/100%, respectively. Treatment-related adverse events
Volume 30 | Supplement 6 | October 2019
O2 1 2
A multicenter retrospective study of Paclitaxel vs. Paclitaxel plus Ramucirumab for advanced gastric cancer patients
Hiroshi Imazeki1, Takeshi Sakamoto2, Michitaka Nakano3, Yuji Negoro4, Satoru Yamaga5, Kentaro Kawakami6, Kazuo Nishikawa7, Naoki Izawa8, Narikazu Boku1, Masahiro Tsuda2, Taito Esaki3, Akitaka Makiyama5, Hiroyuki Okuda6, Takashi Tsuda8, Keiko Minashi9, Shuichi Hironaka7 1 Division of Gastrointestinal Oncology, National Cancer Center Hospital, 2Department of Gastrointestinal Oncology, Hyogo Cancer Center, 3Department of Gastrointestinal and Medical Oncology, National Hospital Organization Kyushu Cancer Center, 4 Department of Gastroenterology, Kochi Health Sciences Center, 5Department of Hematology/Oncology, Japan Community Healthcare Organization Kyushu Hospital, 6 Department of Medical Oncology, Keiyukai Sapporo Hospital, 7Department of Medical Oncology and Hematology, Oita University Faculty of Medicine, 8Department of Clinical Oncology, St.Marianna University School of Medicine, 9Clinical Trial Promotion Department, Chiba Cancer Center Background: Ramucirumab (RAM) conferred survival benefit in patients with advanced gastric cancer (AGC) in the RAINBOW trial (HR 0.807, 95% CI: 0.678-0.962, p ¼ 0.017). However, in the Japanese subpopulation, adding RAM showed modest overall survival (OS) benefit compared with patients in Western country (HR 0.88 vs. 0.73). The objective of this retrospective study was to clarify additional benefit of RAM in clinical practice for Japanese patients. Method: We reviewed medical records of AGC patients who were treated with Paclitaxel (PTX) or PTXþRAM between Jan 2014 and Dec 2016 as second-line treatment in 9 Japanese institutions, excluding patients with prior use of taxane or RAM. Result: A total of 154 patients were included (63 in PTX and 91 in PTXþRAM). Patient characteristics of PTX vs. PTXþRAM groups were: age (median) 64 vs. 64, male 67% vs. 75%, PS (0/1/2) 27/63/10% vs. 30/67/3%, disease status (metastatic/recurrent) 75/ 25% vs. 63/37%, histology (intestinal/diffuse/other) 24/57/19% vs. 31/44/25%, number of metastatic sites (0-2/3) 75/25% vs. 70/30%, ascites (þ/-) 54/46% vs. 50/50%, and platinum combined with fluoropyrimidine in the first line (oxaliplatin/cisplatin) 16/ 84% vs. 37/63%. The median OS in the PTX vs. PTXþRAM groups were 7.0 vs. 9.3 months (HR 0.73, 95% CI: 0.52-1.04, p ¼ 0.083). The median PFS were 3.2 vs. 4.1 months (HR 0.66, 95% CI: 0.47-0.93, p ¼ 0.016). Among 39/55 patients who had measurable lesions, response rate and disease control rate were 18% vs. 35% and 56% vs. 76%, respectively. The proportion of patients receiving subsequent treatment was 57% in PTX group and 59% in PTXþRAM group. Grade 3 or more adverse events were observed more frequently in PTXþRAM group, including neutropenia (55% vs. 21%) and leucopenia (31% vs. 19%) than PTX group. Conclusion: Although this study was retrospective investigation with small sample size, adding RAM to PTX conferred clinically meaningful efficacy and safety in clinical practice for Japanese patients.
O2 1 3
Mismatch repair-deficient or other molecular subtypes and efficacy of chemotherapy for advanced gastric cancer
Yohei Kubota1, Akihito Kawazoe1, Yoshiaki Nakamura1, Akinori Sasaki1, Saori Mishima1, Daisuke Kotani1, Yasutoshi Kuboki1, Hiroya Taniguchi1, Takashi Kojima1, Toshihiko Doi1, Takayuki Yoshino1, Takeshi Kuwata2, Kohei Shitara1 1 Department of Gastroenterology and Gastrointestinal Oncology, National Cancer Center Hospital East, 2Department of Pathology and Clinical Laboratories, National Cancer Center Hospital East Background: Molecular subtypes including mismatch repair-deficient (MMR-D) affect the efficacy of immune checkpoint inhibitors in patients (pts) with advanced gastric cancer (AGC). However, the association between the subtypes and efficacy of standard chemotherapy remains unclear. Methods: AGC pts received chemotherapy from October 2015 to July 2018 with available molecular features were analyzed in this study. We investigated the efficacy of first(fluoropyrimidine þ platinum 6 trastuzumab) or second-line (taxanes 6 ramucirumab or irinotecan) chemotherapy according to four subtypes: MMR-D, EBVþ, HER2þ and others (all-negative). Results: Total 410 pts were analyzed: MMR-D, n ¼ 24 (5.9%); EBVþ, n ¼ 16 (3.9%); HER2þ, n ¼ 56 (13.7%); all-negative, n ¼ 314 (76.6%) with no overlapping between molecular subgroups. Among 285 pts receiving standard first-line chemotherapy, the median PFS were 4.2, 6.0, 7.5, 7.6 months and the ORR were 31, 62, 62, 51% in MMRD, EBVþ, HER2þ, and all-negative groups, respectively. Multivariate analysis showed shorter PFS in MMR-D group vs. all-negative (HR 1.98, 95% confidence interval, 1.133.47; p ¼ 0.016), while other comparison between subgroups did not show significant difference. In 262 pts receiving second-line chemotherapy, there was no significant difference in efficacy among the four subtypes: the median PFS were 3.9, 6.6, 3.7, 3.9
doi:10.1093/annonc/mdz339 | vi85
Downloaded from https://academic.oup.com/annonc/article-abstract/30/Supplement_6/mdz339.013/5583090 by guest on 24 October 2019
Hirofumi Mukai1, Kenichi Inoue2, Masato Takahashi3, Takashi Yamanaka4, Chiyomi Egawa5, Yukinori Sakata6, Hiroki Ikezawa6, Toshiyuki Matsuoka6, Mika Ishii6, Junji Tsurutani7,8 1 National Cancer Center Hospital East, 2Saitama Cancer Center, 3National Hospital Organization Hokkaido Cancer Center, 4Kanagawa Cancer Center, 5Kansai Rosai Hospital, 6Eisai Co., Ltd, 7Showa University, 8Kindai University
tended to occur more frequently in the Jpn subgroups than in the overall cohorts (57%/ 71% in cohorts A/AJpn and 64%/83% in cohorts B/BJpn), but the difference was not statistically significant. There were no treatment-related deaths. Conclusions: Pembro provided safe and durable antitumor activity, even in the Jpn subgroup, with no new safety signals.
Annals of Oncology hyperthyroidism (5.9% vs 0%) and pneumonitis (2.9% vs 0%) in ATZþnPTX and PlaþnPTX, respectively. The incidence of AESI was similar to that of overall study population. Conclusion: The efficacy and safety of ATZþnPTX as first line therapy in Japanese pts with TNBC were consistent with those of overall study population.
O1 9 4
A prospective real-world study of eribulin for HER2-negative recurrent breast cancer patients: final results
[Background]: Two global phase 3 trials (301 trial of first- or second-line eribulin, EMBRACE of third- or later-line eribulin) were carried out during development of eribulin for breast cancer treatment. In this post marketing observation study in Japan, efficacy and safety of eribulin in metastatic breast cancer patients were examined. Additionally, the results were compared with that of phase 3 trials. [Method]: We conducted a prospective study in patients with inoperable or recurrent HER2-negative breast cancer. We enrolled a similar number of patients receiving eribulin as first- or second-line therapy (early line) and those receiving eribulin as third- or later line therapy (later line), and followed the patients for two years (ClinicalTrials.gov Number: NCT02371174). For the overall survival and time to treatment failure, the estimated value of them were calculated by the Kaplan Meier method. The severity of adverse drug events was determined by CTCAE v 4.0. [Results]: During September 2014 to February 2016, 651cases were registered at 182 facilities. In analysis set, 637 patients (319 patients of early line/317 patients of late line/ 1 patient of unknown) was median age of 62.7 (30 - 85) years. Performance status 0/1/ 2/3/4 was seen in 360/234/38/5/0 patients, respectively. Dose reduction were required in 33% of patients. The median overall survival (early line/late line) was 18.8 months/ 12.6 months, respectively, and median time to treatment failure was 4.4 months/3.8 months, respectively. Major side effects (early line/late line) were neutropenia (51%/ 56%), leucopenia (55%/57%), peripheral neuropathy (32%/22%). Grade 3 peripheral neuropathy was 2%. [Conclusion]: The results of overall survival (18.8 months in early line, 12.6 months in later line) in this study is comparable to those of large phase 3 study (15.9 months in 301 trial, 13.1 months in EMBRACE). The incidence of Grade 3 peripheral neuropathy was lower than that of phase 3 trials.
O2 1 1
Pembrolizumab (pembro) in Mismatch Repair-Deficient (dMMR) Advanced Colorectal Cancer (CRC): KEYNOTE-164 Japan Subgroup
Hiroya Taniguchi1, Hiroki Hara2, Takayuki Yoshino1, Kiwamu Akagi3, Kohei Shitara1, Toshiki Masuishi4, Yasutoshi Kuboki1, Takashi Shimamoto5, Kenichi Ueki5, Shi Rong Han5, Kazuo Noguchi5, Luis A. Diaz6 1 Gastroenterology and Gastrointestinal Oncology, National Cancer Center Hospital East, Japan, 2Department of Gastroenterology, Saitama Cancer Center, 3Department of Molecular Diagnosis & Cancer Prevention, Saitama Cancer Center, 4Department of Clinical Oncology, Aichi Cancer Center Hospital, 5Oncology Science Unit, MSD K.K, 6 Department of Translational Medicine, Sidney Kimmel Cancer Center at Johns Hopkins University Background: Pembro is approved for microsatellite instability-high (MSI-H)/dMMR CRC that has progressed on fluoropyrimidineþoxaliplatinþirinotecan (FpþOxþIr), based in part on data from the ongoing phase 2 KEYNOTE-164 study (NCT02460198). The outcomes of the Japan (Jpn) subgroup of patients (pts) with dMMR CRC are reported. Methods: Pts with metastatic MSI-H/dMMR CRC with 2 lines of standard therapy (FpþOxþIr 6 anti-VEGF or anti-EGFR; cohort A) or 1 prior line of therapy (cohort B) received pembro 200 mg every 3 weeks for 2 years or until progression or unacceptable toxicity. Response was assessed every 9 weeks per RECIST v1.1. Primary end point was objective response rate (ORR); secondary end points were duration of response (DOR), disease control rate, progression-free survival (PFS), overall survival (OS), and safety. Data cutoff was February 10, 2017 (cohort A) and September 12, 2017 (cohort B). Results: Of the 124 enrolled pts, the Jpn subgroup comprised 7/61 pts in cohort A (cohort AJpn) and 6/63 pts in cohort B (cohort BJpn). At data cutoff, median followup was 13.2 months/13.2 months for cohorts A/AJpn and 12.6 months/13.6 months for cohorts B/BJpn. ORRs were 28% (95% CI, 20-44; 17 partial responses [PRs]) and 29% (95% CI, 4-71; 2 PRs) for cohorts A and AJpn, respectively, and 32% (95% CI, 21-45; 2 complete responses and 18 PRs) and 67% (95% CI, 22-96; 4 PRs) for cohorts B and BJpn, respectively. Median DOR was not reached for any group. 12-month PFS rates were 34%/29% for cohorts A/AJpn and 41%/67% for cohorts B/BJpn. 12-month OS rates were 72%/57% and 76%/100%, respectively. Treatment-related adverse events
Volume 30 | Supplement 6 | October 2019
O2 1 2
A multicenter retrospective study of Paclitaxel vs. Paclitaxel plus Ramucirumab for advanced gastric cancer patients
Hiroshi Imazeki1, Takeshi Sakamoto2, Michitaka Nakano3, Yuji Negoro4, Satoru Yamaga5, Kentaro Kawakami6, Kazuo Nishikawa7, Naoki Izawa8, Narikazu Boku1, Masahiro Tsuda2, Taito Esaki3, Akitaka Makiyama5, Hiroyuki Okuda6, Takashi Tsuda8, Keiko Minashi9, Shuichi Hironaka7 1 Division of Gastrointestinal Oncology, National Cancer Center Hospital, 2Department of Gastrointestinal Oncology, Hyogo Cancer Center, 3Department of Gastrointestinal and Medical Oncology, National Hospital Organization Kyushu Cancer Center, 4 Department of Gastroenterology, Kochi Health Sciences Center, 5Department of Hematology/Oncology, Japan Community Healthcare Organization Kyushu Hospital, 6 Department of Medical Oncology, Keiyukai Sapporo Hospital, 7Department of Medical Oncology and Hematology, Oita University Faculty of Medicine, 8Department of Clinical Oncology, St.Marianna University School of Medicine, 9Clinical Trial Promotion Department, Chiba Cancer Center Background: Ramucirumab (RAM) conferred survival benefit in patients with advanced gastric cancer (AGC) in the RAINBOW trial (HR 0.807, 95% CI: 0.678-0.962, p ¼ 0.017). However, in the Japanese subpopulation, adding RAM showed modest overall survival (OS) benefit compared with patients in Western country (HR 0.88 vs. 0.73). The objective of this retrospective study was to clarify additional benefit of RAM in clinical practice for Japanese patients. Method: We reviewed medical records of AGC patients who were treated with Paclitaxel (PTX) or PTXþRAM between Jan 2014 and Dec 2016 as second-line treatment in 9 Japanese institutions, excluding patients with prior use of taxane or RAM. Result: A total of 154 patients were included (63 in PTX and 91 in PTXþRAM). Patient characteristics of PTX vs. PTXþRAM groups were: age (median) 64 vs. 64, male 67% vs. 75%, PS (0/1/2) 27/63/10% vs. 30/67/3%, disease status (metastatic/recurrent) 75/ 25% vs. 63/37%, histology (intestinal/diffuse/other) 24/57/19% vs. 31/44/25%, number of metastatic sites (0-2/3) 75/25% vs. 70/30%, ascites (þ/-) 54/46% vs. 50/50%, and platinum combined with fluoropyrimidine in the first line (oxaliplatin/cisplatin) 16/ 84% vs. 37/63%. The median OS in the PTX vs. PTXþRAM groups were 7.0 vs. 9.3 months (HR 0.73, 95% CI: 0.52-1.04, p ¼ 0.083). The median PFS were 3.2 vs. 4.1 months (HR 0.66, 95% CI: 0.47-0.93, p ¼ 0.016). Among 39/55 patients who had measurable lesions, response rate and disease control rate were 18% vs. 35% and 56% vs. 76%, respectively. The proportion of patients receiving subsequent treatment was 57% in PTX group and 59% in PTXþRAM group. Grade 3 or more adverse events were observed more frequently in PTXþRAM group, including neutropenia (55% vs. 21%) and leucopenia (31% vs. 19%) than PTX group. Conclusion: Although this study was retrospective investigation with small sample size, adding RAM to PTX conferred clinically meaningful efficacy and safety in clinical practice for Japanese patients.
O2 1 3
Mismatch repair-deficient or other molecular subtypes and efficacy of chemotherapy for advanced gastric cancer
Yohei Kubota1, Akihito Kawazoe1, Yoshiaki Nakamura1, Akinori Sasaki1, Saori Mishima1, Daisuke Kotani1, Yasutoshi Kuboki1, Hiroya Taniguchi1, Takashi Kojima1, Toshihiko Doi1, Takayuki Yoshino1, Takeshi Kuwata2, Kohei Shitara1 1 Department of Gastroenterology and Gastrointestinal Oncology, National Cancer Center Hospital East, 2Department of Pathology and Clinical Laboratories, National Cancer Center Hospital East Background: Molecular subtypes including mismatch repair-deficient (MMR-D) affect the efficacy of immune checkpoint inhibitors in patients (pts) with advanced gastric cancer (AGC). However, the association between the subtypes and efficacy of standard chemotherapy remains unclear. Methods: AGC pts received chemotherapy from October 2015 to July 2018 with available molecular features were analyzed in this study. We investigated the efficacy of first(fluoropyrimidine þ platinum 6 trastuzumab) or second-line (taxanes 6 ramucirumab or irinotecan) chemotherapy according to four subtypes: MMR-D, EBVþ, HER2þ and others (all-negative). Results: Total 410 pts were analyzed: MMR-D, n ¼ 24 (5.9%); EBVþ, n ¼ 16 (3.9%); HER2þ, n ¼ 56 (13.7%); all-negative, n ¼ 314 (76.6%) with no overlapping between molecular subgroups. Among 285 pts receiving standard first-line chemotherapy, the median PFS were 4.2, 6.0, 7.5, 7.6 months and the ORR were 31, 62, 62, 51% in MMRD, EBVþ, HER2þ, and all-negative groups, respectively. Multivariate analysis showed shorter PFS in MMR-D group vs. all-negative (HR 1.98, 95% confidence interval, 1.133.47; p ¼ 0.016), while other comparison between subgroups did not show significant difference. In 262 pts receiving second-line chemotherapy, there was no significant difference in efficacy among the four subtypes: the median PFS were 3.9, 6.6, 3.7, 3.9
doi:10.1093/annonc/mdz339 | vi85
Downloaded from https://academic.oup.com/annonc/article-abstract/30/Supplement_6/mdz339.013/5583090 by guest on 24 October 2019
Hirofumi Mukai1, Kenichi Inoue2, Masato Takahashi3, Takashi Yamanaka4, Chiyomi Egawa5, Yukinori Sakata6, Hiroki Ikezawa6, Toshiyuki Matsuoka6, Mika Ishii6, Junji Tsurutani7,8 1 National Cancer Center Hospital East, 2Saitama Cancer Center, 3National Hospital Organization Hokkaido Cancer Center, 4Kanagawa Cancer Center, 5Kansai Rosai Hospital, 6Eisai Co., Ltd, 7Showa University, 8Kindai University
tended to occur more frequently in the Jpn subgroups than in the overall cohorts (57%/ 71% in cohorts A/AJpn and 64%/83% in cohorts B/BJpn), but the difference was not statistically significant. There were no treatment-related deaths. Conclusions: Pembro provided safe and durable antitumor activity, even in the Jpn subgroup, with no new safety signals.