- Email: [email protected]
Efficacy of nivolumab for advanced gastric cancer
abstracts Conclusion: This study suggested that nivolumab has a modest effect and is feasible as third line or later line for AGC patients.
P1 026
Efficacy of nivolumab for advanced gastric cancer
Backgrounds: In ATTRACTION-2 trial, nivolumab (NIVO) showed better outcome compared with best supportive care in advanced gastric cancer (AGC) patients (pts) at least two previous regimens. (NIVO has changed the treatment of AGC in Japan.) Methods: From Nov 2017 to Feb 2019, we retrospectively investigated 25 pts with AGC who received NIVO. Results: The patient demographics were as follows: median age, 67 (range, 39-82); male/female ratio, 18:7; performance status (PS) 0/1/2, 9/14/2; unresectable /recurrent, 20 /5; HER2 positive, 3; deep vein thrombosis, 3; intestinal type / diffuse type, 13 /12; primary site EGJ/UML/UM/ML/U/M/L, 2/2/1/3/5/4/8; site of metastases lymph node /liver /peritoneum /ovary, 13 /8 /9 /1; and previous treatment regimens 2 regimens /3 regimens /4 regimens, 9 /10 /6. Response rate (RR) was 12% and disease control rate (DCR) was 28%. The median progression free survival (PFS) was 4.1 months (95% confidence interval [CI], 2.8-NA) and the median overall survival (OS) was 11.8 months (95% CI, 8.2-12.8). In histologic subtypes and PS, there were no difference in PFS and OS between pts with intestinal type and diffuse type as well as between those with PS of 0 and 1-2. As for the number of previous treatment regimens, there was no difference in PFS between pts who received 3 regimens and pts who received 2 regimens. However, the former had significantly longer OS compared with the latter. Ten patients (40%) developed immune-related adverse event (ir-AE) and four (16%) did severe ir-AE (grade 3). Conclusions: The current study showed better results and longer OS for AGC pts who received NIVO with acceptable toxicities. The limitation is a small number of patients accompanied by a potential of selection with retrospective manner, thus warrants a further studies.
P1 046
PF-06439535 (a bevacizumab biosimilar) for non-small cell lung cancer: subgroup analysis
Yoshio Okano1, Tomofumi Ishikawa2, Shintaro Hiro2, Yoko Hirano3, Kentaro Tajima3, Kazuo Kasahara4 1 Division of Pulmonary Medicine, National Hospital Organization Kochi Hospital, 2Pfizer R&D Japan, 3Pfizer Japan Inc, 4Department of Respiratory Medicine, Kanazawa University Graduate School of Medical Sciences, Japan Background: This randomized, double-blind, multicenter study (NCT02364999) compared PF-06439535 (a potential bevacizumab biosimilar) with reference bevacizumab R ), both with paclitaxel and carboplasourced from the EU (bevacizumab-EU; AvastinV tin (P/C) in patients (pts) with advanced non-squamous non-small cell lung cancer (NSCLC). Methods: Eligible pts were randomized (1:1) to PF-06439535 or bevacizumab-EU, both with P/C on Day 1 of a 3-week cycle followed by PF-06439535 of bevacizumab-EU blinded monotherapy until disease progression or unacceptable toxicity. The primary objective was to compare the objective response rate (ORR) by Week 19 between treatment groups, confirmed by Week 25. Subgroup analysis compared the risk ratio (RR) of ORR by gender, age, race, region, smoking history and disease stage. Secondary objectives included safety, 1-year progression-free survival and 1-year survival rate and immunogenicity. Study was ongoing at time of this interim analysis (data cutoff May 8, 2017). Results: In total, 719 pts were randomized to PF-06439535 (n ¼ 358) or bevacizumabEU (n ¼ 361). Pts had a mean age of 61.3 years, 65.0% were male, 76.1% had Stage IV NSCLC and 70.4% were smokers/ex-smokers. Overall, the RR of ORR was 1.015 (95% confidence intervals, 0.863-1.193), which was entirely within the equivalence margin of 0.729-1.371 agreed by the PMDA. Overall, no marked differences in treatment comparisons of ORR were observed across subgroup categories. Secondary efficacy endpoints were similar between treatment groups. Incidence of all-causality treatment-emergent adverse events (AEs) and serious AEs were similar between treatment groups, as well as safety, including immunogenicity. Conclusion: PF-06439535 and bevacizumab-EU showed similar efficacy, safety and immunogenicity in pts with advanced non-squamous NSCLC. Subgroup analysis comparing the RR of ORR by categories supported the results of the primary efficacy endpoint analysis.
vi120 | Poster Session
P1 060
Mutation profile analysis using the OncomineTM Lung cfDNA Assay in advanced NSCLC patients with driver mutation
Yuichi Sakamori1, Masashi Kanai1, Young Hak Kim2, Hironori Yoshida2, Hiroaki Ozasa2, Toyohiro Hirai2, Manabu Muto1 1 Department of clinical oncology, Kyoto University, 2Department of respiratory medicine, Kyoto University Background: The OncomineTM Lung cfDNA Assay (OncomineTM) is a lung cancer specific multi biomarker assay that uses next generation sequencing (NGS). It has been designed to detect gene mutations frequently seen in non small cell lung cancer (NSCLC) with high sensitivity and may be useful for noninvasive detection of driver mutations. Method: The OncomineTM Lung cfDNA Assay was tested using plasma samples obtained from patients with advanced NSCLC confirmed to harbor driver mutations (mutation-positive cases). Driver mutation negative cases were used as negative controls. Results: Among the 16 mutation positive patients, the concordance rate between the tissue assay and OncomineTM assay was 25% (EGFR 2/13, HER2 1/1, BRAF 1/1, KRAS 0/1). Among four mutant negative patients, no driver mutations were reported using OncomineTM. In the two cases with a consistent mutation status between the tissue and OncomineTM assays, plasma samples were obtained at the time of disease progression; in the cases where the mutation status was discordant between the two assays, plasma samples were mainly obtained at a time when the disease was not progressing. Thus, the protocol was amended so that OncomineTM was performed at the time of initial diagnosis or disease progression for EGFR mutation positive patients. In addition, the R EGFR mutation test was performed at the same time point as the OncomineTM cobasV assay as a control. Using this revised protocol, the concordance rate between the tissue assay and OncomineTM assay was 60% for the 5 cases harboring EGFR mutation. In one case, EGFR mutation was reported in the OncomineTM assay, but not in the cobas test. Discussion The concordance rate between tissue and plasma assays, such as OncomineTM, is relatively low if the sampling time points are different. Further investigation is required to establish the optimal plasma sampling time for the plasma assay.
P1 073
Re-administration of EGFR-TKI to mutated EGFR NSCLC patients after remission of osimertinib induced ILD
Kenichi Chikamori, Tadashi Maeda, Kenji Sakamoto, Keisuke Aoe, Toshiaki Utsunomiya, Yoriyuki Murata, Masamoto Nakanishi, Haruhito Kamei NHO Yamaguchi-Ube Medical Center Background: Osimertinib is a key-drug to treat NSCLC harboring EGFR sensitizing mutation at 1st line setting as well as T790M resistant mutation at late line. Interstitial lung disease/pneumonitis (ILD) is a fatal adverse event induced by tyrosine kinase inhibitors including osimertinib especially in the Japanese patients. On the other hand, transient asymptomatic pulmonary opacities (TAPO) caused by osimertinib were reported as relatively frequent (10-20%) phenomenon and usually safe, permitting continuous or "stop and go" treatment with osimertinib. Purpose & Result: We retrospectively analyzed consecutive 60 sonsequtive EGFR mutation positive NSCLC patients treated with osimertinib in our institution by Feb. 2019. Fifteen patients were TKI naı¨ve and the other 45 were pretreated with 1st or 2nd generation EGFR-TKI. ILD occurred in ten (16.7%) patients then administration of osimertinib was interrupted. Corticosteroid was administered to all patients for the ILD, resulting in fully remission of the lung adverse event without any related patient death. Three patients were re-administered with TKI (2 osimertinib for T790M positive, 1 gefitinib for 1st line setting) after remission of ILD. Re-challenged TKI was not successful for these patients resulting in ILD recurrence and permanent cease of TKI treatment. Conclusion: We suggest that strategies other than re-administration of osimertinib should be considered even though osimertinib induced ILD is fully recovered by corticosteroid therapy.
P1 084
Antileukemic activity and mechanism of ardisianone-a crucial role of mitochondrial stress in apoptosis and necroptosis
She-Hung Chan, Jih-Hwa Guh Cosmetic Science Department, Providence University, Taiwan Background: Ardisianone was reported to induce apoptosis in prostate cancer cells, but necroptosis in leukemia cell lines. It is needed to clarify whether ardisianone could cause apoptosis and necroptosis in leukemia cells and investigate its underlying mechanisms. Methods: Cytotoxicity was examined using the MTT assay. Cytoflowmetric analysis of JC-1 and PI staining was used to examine mitochondrial membrane potential and cell cycle progression, respectively. Apoptosis was examined by annexin V-PI staining
Volume 30 | Supplement 6 | October 2019
Downloaded from https://academic.oup.com/annonc/article-abstract/30/Supplement_6/mdz343.009/5582939 by guest on 28 October 2019
Ichiro Moriyama1, Koshi Kawakami2, Fumiyoshi Ikejiri1, Fumimasa Takahashi1, Shinichiro Matsuda1, Norimi Ugata1, Yasumasa Shimasaki1, Yusuke Fujii3, Kousuke Tsukano4, Satoshi Yamanouchi4, Ryusaku Kusunoki4, Youichi Miyaoka5, Ayana Nagamine6, Michina Morioka6, Noriyuki Hirahara3, Ritsuro Suzuki1, Hirofumi Fujishiro4, Atsuo Tokuka6, Akiyoshi Kanazawa6, Yoshitsugu Tajima3, Junji Suzumiya1 1 Innovative Cancer Center, Shimane University Hospital, 2Clinical Oncology, Shimane Prefectural Central Hospital, 3Department of Digestive and General Surgery, Shimane University, Faculty of Medicine, 4Division of Gastroenterology, Shimane Prefectural Central Hospital, 5Division of Endoscopy, Shimane Prefectural Central Hospital, 6 Department of Surgery, Shimane Prefectural Central Hospital
Annals of Oncology
P1 026
Efficacy of nivolumab for advanced gastric cancer
Backgrounds: In ATTRACTION-2 trial, nivolumab (NIVO) showed better outcome compared with best supportive care in advanced gastric cancer (AGC) patients (pts) at least two previous regimens. (NIVO has changed the treatment of AGC in Japan.) Methods: From Nov 2017 to Feb 2019, we retrospectively investigated 25 pts with AGC who received NIVO. Results: The patient demographics were as follows: median age, 67 (range, 39-82); male/female ratio, 18:7; performance status (PS) 0/1/2, 9/14/2; unresectable /recurrent, 20 /5; HER2 positive, 3; deep vein thrombosis, 3; intestinal type / diffuse type, 13 /12; primary site EGJ/UML/UM/ML/U/M/L, 2/2/1/3/5/4/8; site of metastases lymph node /liver /peritoneum /ovary, 13 /8 /9 /1; and previous treatment regimens 2 regimens /3 regimens /4 regimens, 9 /10 /6. Response rate (RR) was 12% and disease control rate (DCR) was 28%. The median progression free survival (PFS) was 4.1 months (95% confidence interval [CI], 2.8-NA) and the median overall survival (OS) was 11.8 months (95% CI, 8.2-12.8). In histologic subtypes and PS, there were no difference in PFS and OS between pts with intestinal type and diffuse type as well as between those with PS of 0 and 1-2. As for the number of previous treatment regimens, there was no difference in PFS between pts who received 3 regimens and pts who received 2 regimens. However, the former had significantly longer OS compared with the latter. Ten patients (40%) developed immune-related adverse event (ir-AE) and four (16%) did severe ir-AE (grade 3). Conclusions: The current study showed better results and longer OS for AGC pts who received NIVO with acceptable toxicities. The limitation is a small number of patients accompanied by a potential of selection with retrospective manner, thus warrants a further studies.
P1 046
PF-06439535 (a bevacizumab biosimilar) for non-small cell lung cancer: subgroup analysis
Yoshio Okano1, Tomofumi Ishikawa2, Shintaro Hiro2, Yoko Hirano3, Kentaro Tajima3, Kazuo Kasahara4 1 Division of Pulmonary Medicine, National Hospital Organization Kochi Hospital, 2Pfizer R&D Japan, 3Pfizer Japan Inc, 4Department of Respiratory Medicine, Kanazawa University Graduate School of Medical Sciences, Japan Background: This randomized, double-blind, multicenter study (NCT02364999) compared PF-06439535 (a potential bevacizumab biosimilar) with reference bevacizumab R ), both with paclitaxel and carboplasourced from the EU (bevacizumab-EU; AvastinV tin (P/C) in patients (pts) with advanced non-squamous non-small cell lung cancer (NSCLC). Methods: Eligible pts were randomized (1:1) to PF-06439535 or bevacizumab-EU, both with P/C on Day 1 of a 3-week cycle followed by PF-06439535 of bevacizumab-EU blinded monotherapy until disease progression or unacceptable toxicity. The primary objective was to compare the objective response rate (ORR) by Week 19 between treatment groups, confirmed by Week 25. Subgroup analysis compared the risk ratio (RR) of ORR by gender, age, race, region, smoking history and disease stage. Secondary objectives included safety, 1-year progression-free survival and 1-year survival rate and immunogenicity. Study was ongoing at time of this interim analysis (data cutoff May 8, 2017). Results: In total, 719 pts were randomized to PF-06439535 (n ¼ 358) or bevacizumabEU (n ¼ 361). Pts had a mean age of 61.3 years, 65.0% were male, 76.1% had Stage IV NSCLC and 70.4% were smokers/ex-smokers. Overall, the RR of ORR was 1.015 (95% confidence intervals, 0.863-1.193), which was entirely within the equivalence margin of 0.729-1.371 agreed by the PMDA. Overall, no marked differences in treatment comparisons of ORR were observed across subgroup categories. Secondary efficacy endpoints were similar between treatment groups. Incidence of all-causality treatment-emergent adverse events (AEs) and serious AEs were similar between treatment groups, as well as safety, including immunogenicity. Conclusion: PF-06439535 and bevacizumab-EU showed similar efficacy, safety and immunogenicity in pts with advanced non-squamous NSCLC. Subgroup analysis comparing the RR of ORR by categories supported the results of the primary efficacy endpoint analysis.
vi120 | Poster Session
P1 060
Mutation profile analysis using the OncomineTM Lung cfDNA Assay in advanced NSCLC patients with driver mutation
Yuichi Sakamori1, Masashi Kanai1, Young Hak Kim2, Hironori Yoshida2, Hiroaki Ozasa2, Toyohiro Hirai2, Manabu Muto1 1 Department of clinical oncology, Kyoto University, 2Department of respiratory medicine, Kyoto University Background: The OncomineTM Lung cfDNA Assay (OncomineTM) is a lung cancer specific multi biomarker assay that uses next generation sequencing (NGS). It has been designed to detect gene mutations frequently seen in non small cell lung cancer (NSCLC) with high sensitivity and may be useful for noninvasive detection of driver mutations. Method: The OncomineTM Lung cfDNA Assay was tested using plasma samples obtained from patients with advanced NSCLC confirmed to harbor driver mutations (mutation-positive cases). Driver mutation negative cases were used as negative controls. Results: Among the 16 mutation positive patients, the concordance rate between the tissue assay and OncomineTM assay was 25% (EGFR 2/13, HER2 1/1, BRAF 1/1, KRAS 0/1). Among four mutant negative patients, no driver mutations were reported using OncomineTM. In the two cases with a consistent mutation status between the tissue and OncomineTM assays, plasma samples were obtained at the time of disease progression; in the cases where the mutation status was discordant between the two assays, plasma samples were mainly obtained at a time when the disease was not progressing. Thus, the protocol was amended so that OncomineTM was performed at the time of initial diagnosis or disease progression for EGFR mutation positive patients. In addition, the R EGFR mutation test was performed at the same time point as the OncomineTM cobasV assay as a control. Using this revised protocol, the concordance rate between the tissue assay and OncomineTM assay was 60% for the 5 cases harboring EGFR mutation. In one case, EGFR mutation was reported in the OncomineTM assay, but not in the cobas test. Discussion The concordance rate between tissue and plasma assays, such as OncomineTM, is relatively low if the sampling time points are different. Further investigation is required to establish the optimal plasma sampling time for the plasma assay.
P1 073
Re-administration of EGFR-TKI to mutated EGFR NSCLC patients after remission of osimertinib induced ILD
Kenichi Chikamori, Tadashi Maeda, Kenji Sakamoto, Keisuke Aoe, Toshiaki Utsunomiya, Yoriyuki Murata, Masamoto Nakanishi, Haruhito Kamei NHO Yamaguchi-Ube Medical Center Background: Osimertinib is a key-drug to treat NSCLC harboring EGFR sensitizing mutation at 1st line setting as well as T790M resistant mutation at late line. Interstitial lung disease/pneumonitis (ILD) is a fatal adverse event induced by tyrosine kinase inhibitors including osimertinib especially in the Japanese patients. On the other hand, transient asymptomatic pulmonary opacities (TAPO) caused by osimertinib were reported as relatively frequent (10-20%) phenomenon and usually safe, permitting continuous or "stop and go" treatment with osimertinib. Purpose & Result: We retrospectively analyzed consecutive 60 sonsequtive EGFR mutation positive NSCLC patients treated with osimertinib in our institution by Feb. 2019. Fifteen patients were TKI naı¨ve and the other 45 were pretreated with 1st or 2nd generation EGFR-TKI. ILD occurred in ten (16.7%) patients then administration of osimertinib was interrupted. Corticosteroid was administered to all patients for the ILD, resulting in fully remission of the lung adverse event without any related patient death. Three patients were re-administered with TKI (2 osimertinib for T790M positive, 1 gefitinib for 1st line setting) after remission of ILD. Re-challenged TKI was not successful for these patients resulting in ILD recurrence and permanent cease of TKI treatment. Conclusion: We suggest that strategies other than re-administration of osimertinib should be considered even though osimertinib induced ILD is fully recovered by corticosteroid therapy.
P1 084
Antileukemic activity and mechanism of ardisianone-a crucial role of mitochondrial stress in apoptosis and necroptosis
She-Hung Chan, Jih-Hwa Guh Cosmetic Science Department, Providence University, Taiwan Background: Ardisianone was reported to induce apoptosis in prostate cancer cells, but necroptosis in leukemia cell lines. It is needed to clarify whether ardisianone could cause apoptosis and necroptosis in leukemia cells and investigate its underlying mechanisms. Methods: Cytotoxicity was examined using the MTT assay. Cytoflowmetric analysis of JC-1 and PI staining was used to examine mitochondrial membrane potential and cell cycle progression, respectively. Apoptosis was examined by annexin V-PI staining
Volume 30 | Supplement 6 | October 2019
Downloaded from https://academic.oup.com/annonc/article-abstract/30/Supplement_6/mdz343.009/5582939 by guest on 28 October 2019
Ichiro Moriyama1, Koshi Kawakami2, Fumiyoshi Ikejiri1, Fumimasa Takahashi1, Shinichiro Matsuda1, Norimi Ugata1, Yasumasa Shimasaki1, Yusuke Fujii3, Kousuke Tsukano4, Satoshi Yamanouchi4, Ryusaku Kusunoki4, Youichi Miyaoka5, Ayana Nagamine6, Michina Morioka6, Noriyuki Hirahara3, Ritsuro Suzuki1, Hirofumi Fujishiro4, Atsuo Tokuka6, Akiyoshi Kanazawa6, Yoshitsugu Tajima3, Junji Suzumiya1 1 Innovative Cancer Center, Shimane University Hospital, 2Clinical Oncology, Shimane Prefectural Central Hospital, 3Department of Digestive and General Surgery, Shimane University, Faculty of Medicine, 4Division of Gastroenterology, Shimane Prefectural Central Hospital, 5Division of Endoscopy, Shimane Prefectural Central Hospital, 6 Department of Surgery, Shimane Prefectural Central Hospital
Annals of Oncology