TY - JOUR
T1 - Impact of Brain Metastases on Treatment Patterns and Outcomes With First-Line Durvalumab Plus Platinum-Etoposide in Extensive-Stage SCLC (CASPIAN)
T2 - A Brief Report
AU - Chen, Yuanbin
AU - Paz-Ares, Luis
AU - Reinmuth, Niels
AU - Garassino, Marina Chiara
AU - Statsenko, Galina
AU - Hochmair, Maximilian J.
AU - Özgüroğlu, Mustafa
AU - Verderame, Francesco
AU - Havel, Libor
AU - Losonczy, György
AU - Conev, Nikolay V.
AU - Hotta, Katsuyuki
AU - Ji, Jun Ho
AU - Spencer, Stuart
AU - Dalvi, Tapashi
AU - Jiang, Haiyi
AU - Goldman, Jonathan W.
N1 - Funding Information:
Disclosure: Dr. Chen reports receiving honoraria from Amgen, United States , AstraZeneca, United Kingdom , Bristol-Myers Squibb , Guardant Health , Jazz Pharmaceutical , Merck, United States , Pfizer , and Takeda and a research contract and support for meeting attendance/travel from Ipsen, France , all outside the submitted work. Dr. Paz-Ares reports receiving grants from AstraZeneca , Bristol-Myers Squibb , Merck Sharp & Dohme, United Kingdom , and Pfizer ; consulting fees from Amgen, AstraZeneca, Bayer, Blueprint Medicines, Bristol-Myers Squibb, Ipsen, Eli Lilly, Merck, Mirati, Merck Sharp & Dohme, Novartis, Pfizer, PharmaMar, Roche, Sanofi, and Servier, France; honoraria from AstraZeneca, Janssen, Merck, Mirati, and Sanofi; and reports having a leadership role with Genomica and Altum Sequencing, all outside the submitted work. Dr. Reinmuth reports receiving honoraria from Amgen, AstraZeneca, Boehringer Ingelheim, Germany, Bristol-Myers Squibb, Daiichi Sankyo, Eli Lilly, Hoffmann-La Roche, Merck, Merck Sharp & Dohme, Pfizer, and Takeda and consulting fees from Amgen, AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Daiichi Sankyo, Hoffmann-La Roche, Merck, Merck Sharp & Dohme, Pfizer, and Takeda, Japan, all outside the submitted work. Dr. Garassino reports receiving grants from AstraZeneca and Merck and personal fees from AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Eli Lilly, GlaxoSmithKline, United Kingdom, Merck, Novartis, Pfizer, Roche, and Takeda, all outside the submitted work. Dr. Hochmair reports receiving speakers’ honoraria from AstraZeneca, Boehringer Ingelheim, Merck Sharp & Dohme, Pfizer, Roche, and Takeda outside the submitted work. Dr. Verderame reports receiving grants from Roche SpA , Boehringer Ingelheim , Servier , AstraZeneca , GlaxoSmithKline , Takeda , and Merck Sharp & Dohme , all outside the submitted work. Dr. Hotta reports receiving grants and personal fees from AstraZeneca during the conduct of the study; grants from Bristol-Myers Squibb , Chugai, Japan , Eli Lilly , and Merck Sharp & Dohme outside the submitted work; and honoraria from AstraZeneca , Boehringer Ingelheim , Bristol-Myers Squibb , Chugai , Eli Lilly , Merck Sharp & Dohme , Nippon Kayaku, Japan , Ono , Pfizer, United States , Taiho , and Takeda outside the submitted work. Mr. Spencer and Dr. Dalvi report full-time employment and stock ownership with AstraZeneca. Dr. Jiang reports full-time employment and stock ownership with AstraZeneca and a patent pending for the CASPIAN study trial design. Dr. Goldman reports receiving research grants from AbbVie, United States , AstraZeneca , Bristol-Myers Squibb, United States , Genentech, United States , and Merck ; consulting fees from AbbVie, AstraZeneca, Bristol-Myers Squibb, and Genentech; and support for travel from AstraZeneca , all outside the submitted work. The remaining authors declare no conflict of interest.
Funding Information:
This study (NCT03043872) was sponsored by AstraZeneca . The authors thank the patients, their families, and caregivers. Medical writing support, under the direction of the authors, was provided by Andrew Gannon and Craig Turner of Ashfield MedComms (New York, NY), an Ashfield Health company, and was funded by AstraZeneca.
Funding Information:
Disclosure: Dr. Chen reports receiving honoraria from Amgen, United States, AstraZeneca, United Kingdom, Bristol-Myers Squibb, Guardant Health, Jazz Pharmaceutical, Merck, United States, Pfizer, and Takeda and a research contract and support for meeting attendance/travel from Ipsen, France, all outside the submitted work. Dr. Paz-Ares reports receiving grants from AstraZeneca, Bristol-Myers Squibb, Merck Sharp & Dohme, United Kingdom, and Pfizer; consulting fees from Amgen, AstraZeneca, Bayer, Blueprint Medicines, Bristol-Myers Squibb, Ipsen, Eli Lilly, Merck, Mirati, Merck Sharp & Dohme, Novartis, Pfizer, PharmaMar, Roche, Sanofi, and Servier, France; honoraria from AstraZeneca, Janssen, Merck, Mirati, and Sanofi; and reports having a leadership role with Genomica and Altum Sequencing, all outside the submitted work. Dr. Reinmuth reports receiving honoraria from Amgen, AstraZeneca, Boehringer Ingelheim, Germany, Bristol-Myers Squibb, Daiichi Sankyo, Eli Lilly, Hoffmann-La Roche, Merck, Merck Sharp & Dohme, Pfizer, and Takeda and consulting fees from Amgen, AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Daiichi Sankyo, Hoffmann-La Roche, Merck, Merck Sharp & Dohme, Pfizer, and Takeda, Japan, all outside the submitted work. Dr. Garassino reports receiving grants from AstraZeneca and Merck and personal fees from AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Eli Lilly, GlaxoSmithKline, United Kingdom, Merck, Novartis, Pfizer, Roche, and Takeda, all outside the submitted work. Dr. Hochmair reports receiving speakers’ honoraria from AstraZeneca, Boehringer Ingelheim, Merck Sharp & Dohme, Pfizer, Roche, and Takeda outside the submitted work. Dr. Verderame reports receiving grants from Roche SpA, Boehringer Ingelheim, Servier, AstraZeneca, GlaxoSmithKline, Takeda, and Merck Sharp & Dohme, all outside the submitted work. Dr. Hotta reports receiving grants and personal fees from AstraZeneca during the conduct of the study; grants from Bristol-Myers Squibb, Chugai, Japan, Eli Lilly, and Merck Sharp & Dohme outside the submitted work; and honoraria from AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Chugai, Eli Lilly, Merck Sharp & Dohme, Nippon Kayaku, Japan, Ono, Pfizer, United States, Taiho, and Takeda outside the submitted work. Mr. Spencer and Dr. Dalvi report full-time employment and stock ownership with AstraZeneca. Dr. Jiang reports full-time employment and stock ownership with AstraZeneca and a patent pending for the CASPIAN study trial design. Dr. Goldman reports receiving research grants from AbbVie, United States, AstraZeneca, Bristol-Myers Squibb, United States, Genentech, United States, and Merck; consulting fees from AbbVie, AstraZeneca, Bristol-Myers Squibb, and Genentech; and support for travel from AstraZeneca, all outside the submitted work. The remaining authors declare no conflict of interest.This study (NCT03043872) was sponsored by AstraZeneca. The authors thank the patients, their families, and caregivers. Medical writing support, under the direction of the authors, was provided by Andrew Gannon and Craig Turner of Ashfield MedComms (New York, NY), an Ashfield Health company, and was funded by AstraZeneca.
Publisher Copyright:
© 2022 The Authors
PY - 2022/6
Y1 - 2022/6
N2 - Introduction: In the phase 3 study involving the use of durvalumab with or without tremelimumab in combination with platinum-based chemotherapy in untreated extensive-stage SCLC (CASPIAN study), first-line durvalumab plus platinum-etoposide (EP) significantly improved overall survival (OS) versus EP alone (p = 0.0047). We report exploratory subgroup analyses of treatment patterns and outcomes according to the presence of baseline brain or central nervous system metastases. Methods: Patients (WHO performance status 0 or 1), including those with asymptomatic or treated-and-stable brain metastases, were randomized to four cycles of durvalumab plus EP followed by maintenance durvalumab until progression or up to six cycles of EP and optional prophylactic cranial irradiation. Prespecified analyses of OS and progression-free survival (PFS) in subgroups with or without brain metastases used unstratified-Cox proportional hazards models. The data cutoff was on January 27, 2020. Results: At baseline, 28 out of 268 patients (10.4%) in the durvalumab plus EP arm and 27 out of 269 patients (10.0%) in the EP arm had known brain metastases, of whom 3 of 28 (10.7%) and 4 of 27 (14.8%) had previous brain radiotherapy, respectively. Durvalumab plus EP (versus EP alone) prolonged OS (hazard ratio, 95% confidence interval) in patients with (0.79, 0.44–1.41) or without (0.76, 0.62–0.92) brain metastases, with similar PFS results (0.73, 0.42–1.29 and 0.80, 0.66–0.97, respectively). Among patients without brain metastases, similar proportions in each arm developed new brain lesions as part of their first progression (8.8% and 9.5%), although 8.3% in the EP arm received prophylactic cranial irradiation. Similar proportions in each arm received subsequent brain radiotherapy (20.5% and 21.2%), although more common in patients with than without baseline brain metastases (45.5% and 18.0%). Conclusions: The OS and PFS benefit with first-line durvalumab plus EP were maintained irrespective of the presence of brain metastases, further supporting its standard-of-care use.
AB - Introduction: In the phase 3 study involving the use of durvalumab with or without tremelimumab in combination with platinum-based chemotherapy in untreated extensive-stage SCLC (CASPIAN study), first-line durvalumab plus platinum-etoposide (EP) significantly improved overall survival (OS) versus EP alone (p = 0.0047). We report exploratory subgroup analyses of treatment patterns and outcomes according to the presence of baseline brain or central nervous system metastases. Methods: Patients (WHO performance status 0 or 1), including those with asymptomatic or treated-and-stable brain metastases, were randomized to four cycles of durvalumab plus EP followed by maintenance durvalumab until progression or up to six cycles of EP and optional prophylactic cranial irradiation. Prespecified analyses of OS and progression-free survival (PFS) in subgroups with or without brain metastases used unstratified-Cox proportional hazards models. The data cutoff was on January 27, 2020. Results: At baseline, 28 out of 268 patients (10.4%) in the durvalumab plus EP arm and 27 out of 269 patients (10.0%) in the EP arm had known brain metastases, of whom 3 of 28 (10.7%) and 4 of 27 (14.8%) had previous brain radiotherapy, respectively. Durvalumab plus EP (versus EP alone) prolonged OS (hazard ratio, 95% confidence interval) in patients with (0.79, 0.44–1.41) or without (0.76, 0.62–0.92) brain metastases, with similar PFS results (0.73, 0.42–1.29 and 0.80, 0.66–0.97, respectively). Among patients without brain metastases, similar proportions in each arm developed new brain lesions as part of their first progression (8.8% and 9.5%), although 8.3% in the EP arm received prophylactic cranial irradiation. Similar proportions in each arm received subsequent brain radiotherapy (20.5% and 21.2%), although more common in patients with than without baseline brain metastases (45.5% and 18.0%). Conclusions: The OS and PFS benefit with first-line durvalumab plus EP were maintained irrespective of the presence of brain metastases, further supporting its standard-of-care use.
KW - Brain metastases
KW - CASPIAN
KW - Central nervous system
KW - Extensive-stage SCLC
KW - Immunotherapy
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U2 - 10.1016/j.jtocrr.2022.100330
DO - 10.1016/j.jtocrr.2022.100330
M3 - Article
AN - SCOPUS:85131958889
VL - 3
JO - JTO Clinical and Research Reports
JF - JTO Clinical and Research Reports
SN - 2666-3643
IS - 6
M1 - 100330
ER -