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Refractory Acute Myeloid Leukemia: QuANTUM-R Trial Results
abstracts
Annals of Oncology Conclusions: This is the first study to evaluate the impact of the 12-RS assay on adjuvant treatment recommendations for stage III CC. The 12-RS results significantly influenced treatment recommendations.
PS2 3½Encore
Quizartinib in FLT3-ITD-Mutated Relapsed/Refractory Acute Myeloid Leukemia: QuANTUM-R Trial Results
Background: FLT3-ITD mutations occur in about 25% of patients (pts) with acute myeloid leukemia (AML) and are associated with poor outcomes. Pts with relapsed/ refractory (R/R) FLT3-ITD AML have worse prognosis and high unmet medical need. Quizartinib (Q) is a potent and selective FLT3i with promising activity and a manageable safety profile. QuANTUM-R was a global, phase 3, randomized trial of Q vs chemotherapy (SC) in pts with R/R FLT3-ITD AML (NCT02039726). Methods: Pts with R/R FLT3-ITD AML w/wo hematopoietic stem cell transplant (HSCT) were randomized to receive Q or a preselected investigator choice SC: lowdose cytarabine; mitoxantrone, etoposide, and intermediate-dose cytarabine (MEC); or fludarabine, cytarabine, and G-CSF with idarubicin (FLAG-IDA). Prior midostaurin was allowed. Pts receiving HSCT after Q could resume Q after HSCT. Primary and secondary endpoints were overall survival (OS) and event-free survival (EFS), respectively. Exploratory endpoints included response rate, time to and duration of response, and transplant rate. Results: 367 pts were randomized; 245 to Q and 122 to SC. Median follow-up was 23.5 mo. OS hazard ratio (HR) of Q relative to SC was 0.76 (95% CI, 0.58-0.98; P¼.0177). Median OS was 6.2 (95% CI, 5.3-7.2) vs 4.7 (95% CI, 4.0-5.5) mo in Q and SC arms, respectively. EFS HR was 0.90 (95% CI, 0.70-1.16; P¼.1071); median EFS was 1.4 (95% CI, 0.0-1.9) vs 0.9 (95% CI, 0.4-1.3) mo, respectively. Sensitivity analyses and OS subgroup analyses supported Q vs SC. Composite complete response (CRc) was
Volume 30 | Supplement 6 | October 2019
PS3 2
KN100: Results from Japanese patients with advanced recurrent ovarian cancer treated with pembrolizumab monotherapy
Koji Matsumoto1, Shin Nishio2, Kazuhiro Takehara3, Naoki Kawamura4, Kosei Hasegawa5, Nobuhiro Takeshima6, Daisuke Aoki7, Shoji Kamiura8, Atsushi Arakawa9, Eiji Kondo10, Tomoko Hirakawa11, Keiko Yamamoto12, Shi Rong Han12, Karen Stein13, Stephen Keefe13, Jonathan Lederman14, Ursula Matulonis15, Keiichi Fujiwara5 1 Hyogo Cancer Center, Akashi, Japan, United States, 2Kurume University Hospital, Kurume, Japan, 3National Hospital Organization Shikoku Cancer Center, Matsuyama, Japan, 4Osaka City General Hospital, Osaka, Japan, 5Saitama Medical University International Medical Center, Hidaka, Japan, 6Cancer Institute Hospital of JFCR, Tokyo, Japan, 7Keio University Hospital, Tokyo, Japan, 8Osaka International Cancer Institute, Osaka, Japan, 9Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan, 10Mie University Hospital, Tsu, Japan, 11Oita University Hospital, Yufu, Japan, 12 MSD K.K., Tokyo, Japan, 13Merck & Co., Inc., Kenilworth, NJ, USA, 14University College London Cancer Institute, London, UK, 15Dana-Farber Cancer Institute, Boston, MA, USA Background: Interim results from the ongoing, 2-cohort, phase 2 KEYNOTE-100 study (NCT02674061) have suggested clinical efficacy of pembrolizumab (pembro) monotherapy in some patients (pts) with advanced ovarian cancer (AOC). Here, we present efficacy and safety results from Japanese pts in KEYNOTE-100. Methods: Pts with epithelial AOC, fallopian tube cancer, or primary peritoneal cancer with prior treatment with debulking surgery followed by front-line platinum-based chemotherapy (CT) and documented disease recurrence were eligible for this study. Cohort A received 2 prior CT lines and had a platinum- or treatment-free interval (PFI; TFI) of 3-12 months. Cohort B received 3-5 prior CT lines and had a PFI/TFI of 3 months. All pts received pembro 200 mg every 3 weeks as monotherapy for 2 years or until progression, death, unacceptable toxicity, or consent withdrawal. The primary objectives were ORR per RECIST v1.1 by blinded independent central review for each cohort and by tumor PD-L1 expression. The relationship between PD-L1 expression (defined as combined positive score [CPS]) and ORR was assessed. Results: In the second interim analysis (Matalounis, ASCO 2018) of the overall study population (N ¼ 376), the ORR in Cohort A and B were 7% (95% CI, 5-11; n ¼ 285) and 10% (95% CI, 5-18; n ¼ 91), respectively. 21 Japanese pts were treated (19 in Cohort A; 2 in Cohort B). Mean (SD) age was 57 (10) years; 91% had ECOG PS 0, and 76% had stage 3-4 disease. The ORR in all pts was 19% (95% CI, 5-42). ORR increased with increasing PD-L1 expression: 25% (2/8) with CPS 1 and 50% (1/2) with CPS 10. 62% of pts had treatment-related adverse events (TRAEs), and 24% had grade 3-5 TRAEs. There were no treatment-related deaths in this subpopulation. Conclusion: Pembro monotherapy was associated with antitumor activity in Japanese pts with recurrent AOC, with no new safety signals identified in this subpopulation. There was a potential trend associated with ORR and PD-L1 expression.
doi:10.1093/annonc/mdz374 | vi81
Downloaded from https://academic.oup.com/annonc/article-abstract/30/Supplement_6/mdz374.003/5583084 by guest on 24 October 2019
Jorge E. Cortes1, Samer Khaled2, Giovanni Martinelli3, Alexander E Perl4, Siddhartha Ganguly5, Nigel H Russell6, Alwin Kramer7, Herve Dombret8, Donna Hogge9, Brian A Jonas10, Anskar Yh Leung11, Priyanka Mehta12, Pau Montesinos13, Markus P Radsak14, Simona Sica15, Meena Arunachalam16, Melissa Holmes16, Ruth Namuyinga16, Yufen Zhang16, Mark J Levis17 1 Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX, United States, 2Department of Hematology/HCT, City of Hope National Medical Center, Duarte, CA, 3Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy, 4Division of Hematology-Oncology/Department of Medicine, University of Pennsylvania, Philadelphia, PA, 5University of Kansas Medical Center, Westwood, KS, 6Nottingham University Hospital, Nottingham, United Kingdom, 7 Klinische Kooperationseinheit Molekulare Haematologie/Onkologie, Medizinische Klinik V, Universitat Heidelberg and German Cancer Research Center (DKFZ), Heidelberg, Germany, 8University Paris Diderot, Saint-Louis Hospital, Paris, France, 9Vancouver General Hospital, Vancouver, Canada, 10University of California Davis Comprehensive Cancer Center Sacramento, CA, USA, 11The University of Hong Kong, Hong Kong, China, 12The University of Bristol, Bristol, United Kingdom, 13Hospital Universitari i Politecnic La Fe, Valencia, Spain, 14Department of Hematology, Medical Oncology, & Pneumology, University Medical Center of the Johannes Gutenberg University, Mainz, Germany, 15Hematology Department, Fondazione Policlinico Universitario A. Gemelli IRCCS - Universita Cattolica del Sacro Cuore, Roma, Italy, 16Daiichi Sankyo, Inc., Basking Ridge, NJ, 17Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD
48% and 27% in Q and SC arms, respectively. Transplant rate was 32% (Q) and 12% (SC). Median time to first CRc was 4.9 wk for Q. The most common grade 3 TEAEs in both arms were infections and those associated with cytopenia. Conclusion: OS benefit was observed with single-agent Q vs SC in pts with R/R FLT3ITD AML with a favorable Q safety profile, providing evidence of meaningful clinical benefit in pts with limited treatment options.
Annals of Oncology Conclusions: This is the first study to evaluate the impact of the 12-RS assay on adjuvant treatment recommendations for stage III CC. The 12-RS results significantly influenced treatment recommendations.
PS2 3½Encore
Quizartinib in FLT3-ITD-Mutated Relapsed/Refractory Acute Myeloid Leukemia: QuANTUM-R Trial Results
Background: FLT3-ITD mutations occur in about 25% of patients (pts) with acute myeloid leukemia (AML) and are associated with poor outcomes. Pts with relapsed/ refractory (R/R) FLT3-ITD AML have worse prognosis and high unmet medical need. Quizartinib (Q) is a potent and selective FLT3i with promising activity and a manageable safety profile. QuANTUM-R was a global, phase 3, randomized trial of Q vs chemotherapy (SC) in pts with R/R FLT3-ITD AML (NCT02039726). Methods: Pts with R/R FLT3-ITD AML w/wo hematopoietic stem cell transplant (HSCT) were randomized to receive Q or a preselected investigator choice SC: lowdose cytarabine; mitoxantrone, etoposide, and intermediate-dose cytarabine (MEC); or fludarabine, cytarabine, and G-CSF with idarubicin (FLAG-IDA). Prior midostaurin was allowed. Pts receiving HSCT after Q could resume Q after HSCT. Primary and secondary endpoints were overall survival (OS) and event-free survival (EFS), respectively. Exploratory endpoints included response rate, time to and duration of response, and transplant rate. Results: 367 pts were randomized; 245 to Q and 122 to SC. Median follow-up was 23.5 mo. OS hazard ratio (HR) of Q relative to SC was 0.76 (95% CI, 0.58-0.98; P¼.0177). Median OS was 6.2 (95% CI, 5.3-7.2) vs 4.7 (95% CI, 4.0-5.5) mo in Q and SC arms, respectively. EFS HR was 0.90 (95% CI, 0.70-1.16; P¼.1071); median EFS was 1.4 (95% CI, 0.0-1.9) vs 0.9 (95% CI, 0.4-1.3) mo, respectively. Sensitivity analyses and OS subgroup analyses supported Q vs SC. Composite complete response (CRc) was
Volume 30 | Supplement 6 | October 2019
PS3 2
KN100: Results from Japanese patients with advanced recurrent ovarian cancer treated with pembrolizumab monotherapy
Koji Matsumoto1, Shin Nishio2, Kazuhiro Takehara3, Naoki Kawamura4, Kosei Hasegawa5, Nobuhiro Takeshima6, Daisuke Aoki7, Shoji Kamiura8, Atsushi Arakawa9, Eiji Kondo10, Tomoko Hirakawa11, Keiko Yamamoto12, Shi Rong Han12, Karen Stein13, Stephen Keefe13, Jonathan Lederman14, Ursula Matulonis15, Keiichi Fujiwara5 1 Hyogo Cancer Center, Akashi, Japan, United States, 2Kurume University Hospital, Kurume, Japan, 3National Hospital Organization Shikoku Cancer Center, Matsuyama, Japan, 4Osaka City General Hospital, Osaka, Japan, 5Saitama Medical University International Medical Center, Hidaka, Japan, 6Cancer Institute Hospital of JFCR, Tokyo, Japan, 7Keio University Hospital, Tokyo, Japan, 8Osaka International Cancer Institute, Osaka, Japan, 9Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan, 10Mie University Hospital, Tsu, Japan, 11Oita University Hospital, Yufu, Japan, 12 MSD K.K., Tokyo, Japan, 13Merck & Co., Inc., Kenilworth, NJ, USA, 14University College London Cancer Institute, London, UK, 15Dana-Farber Cancer Institute, Boston, MA, USA Background: Interim results from the ongoing, 2-cohort, phase 2 KEYNOTE-100 study (NCT02674061) have suggested clinical efficacy of pembrolizumab (pembro) monotherapy in some patients (pts) with advanced ovarian cancer (AOC). Here, we present efficacy and safety results from Japanese pts in KEYNOTE-100. Methods: Pts with epithelial AOC, fallopian tube cancer, or primary peritoneal cancer with prior treatment with debulking surgery followed by front-line platinum-based chemotherapy (CT) and documented disease recurrence were eligible for this study. Cohort A received 2 prior CT lines and had a platinum- or treatment-free interval (PFI; TFI) of 3-12 months. Cohort B received 3-5 prior CT lines and had a PFI/TFI of 3 months. All pts received pembro 200 mg every 3 weeks as monotherapy for 2 years or until progression, death, unacceptable toxicity, or consent withdrawal. The primary objectives were ORR per RECIST v1.1 by blinded independent central review for each cohort and by tumor PD-L1 expression. The relationship between PD-L1 expression (defined as combined positive score [CPS]) and ORR was assessed. Results: In the second interim analysis (Matalounis, ASCO 2018) of the overall study population (N ¼ 376), the ORR in Cohort A and B were 7% (95% CI, 5-11; n ¼ 285) and 10% (95% CI, 5-18; n ¼ 91), respectively. 21 Japanese pts were treated (19 in Cohort A; 2 in Cohort B). Mean (SD) age was 57 (10) years; 91% had ECOG PS 0, and 76% had stage 3-4 disease. The ORR in all pts was 19% (95% CI, 5-42). ORR increased with increasing PD-L1 expression: 25% (2/8) with CPS 1 and 50% (1/2) with CPS 10. 62% of pts had treatment-related adverse events (TRAEs), and 24% had grade 3-5 TRAEs. There were no treatment-related deaths in this subpopulation. Conclusion: Pembro monotherapy was associated with antitumor activity in Japanese pts with recurrent AOC, with no new safety signals identified in this subpopulation. There was a potential trend associated with ORR and PD-L1 expression.
doi:10.1093/annonc/mdz374 | vi81
Downloaded from https://academic.oup.com/annonc/article-abstract/30/Supplement_6/mdz374.003/5583084 by guest on 24 October 2019
Jorge E. Cortes1, Samer Khaled2, Giovanni Martinelli3, Alexander E Perl4, Siddhartha Ganguly5, Nigel H Russell6, Alwin Kramer7, Herve Dombret8, Donna Hogge9, Brian A Jonas10, Anskar Yh Leung11, Priyanka Mehta12, Pau Montesinos13, Markus P Radsak14, Simona Sica15, Meena Arunachalam16, Melissa Holmes16, Ruth Namuyinga16, Yufen Zhang16, Mark J Levis17 1 Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX, United States, 2Department of Hematology/HCT, City of Hope National Medical Center, Duarte, CA, 3Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy, 4Division of Hematology-Oncology/Department of Medicine, University of Pennsylvania, Philadelphia, PA, 5University of Kansas Medical Center, Westwood, KS, 6Nottingham University Hospital, Nottingham, United Kingdom, 7 Klinische Kooperationseinheit Molekulare Haematologie/Onkologie, Medizinische Klinik V, Universitat Heidelberg and German Cancer Research Center (DKFZ), Heidelberg, Germany, 8University Paris Diderot, Saint-Louis Hospital, Paris, France, 9Vancouver General Hospital, Vancouver, Canada, 10University of California Davis Comprehensive Cancer Center Sacramento, CA, USA, 11The University of Hong Kong, Hong Kong, China, 12The University of Bristol, Bristol, United Kingdom, 13Hospital Universitari i Politecnic La Fe, Valencia, Spain, 14Department of Hematology, Medical Oncology, & Pneumology, University Medical Center of the Johannes Gutenberg University, Mainz, Germany, 15Hematology Department, Fondazione Policlinico Universitario A. Gemelli IRCCS - Universita Cattolica del Sacro Cuore, Roma, Italy, 16Daiichi Sankyo, Inc., Basking Ridge, NJ, 17Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD
48% and 27% in Q and SC arms, respectively. Transplant rate was 32% (Q) and 12% (SC). Median time to first CRc was 4.9 wk for Q. The most common grade 3 TEAEs in both arms were infections and those associated with cytopenia. Conclusion: OS benefit was observed with single-agent Q vs SC in pts with R/R FLT3ITD AML with a favorable Q safety profile, providing evidence of meaningful clinical benefit in pts with limited treatment options.