TY - JOUR
T1 - Phase II trial of cediranib in combination with cisplatin and pemetrexed in chemotherapy-naïve patients with unresectable malignant pleural mesothelioma (SWOG S0905)
AU - SWOG investigators
AU - Tsao, Anne S.
AU - Miao, Jieling
AU - Wistuba, Ignacio I.
AU - Vogelzang, Nicholas J.
AU - Heymach, John V.
AU - Fossella, Frank V.
AU - Lu, Charles
AU - Velasco, Mario R.
AU - Box-Noriega, Brandy
AU - Hueftle, James G.
AU - Gadgeel, Shirish
AU - Redman, Mary W.
AU - Gandara, David R.
AU - Kelly, Karen
N1 - Publisher Copyright:
© 2019 by American Society of Clinical Oncology
PY - 2019/10/1
Y1 - 2019/10/1
N2 - PURPOSE Antiangiogenic agents combined with chemotherapy have efficacy in the treatment of unresectable malignant pleural mesothelioma (MPM). Cediranib (AstraZeneca, Cheshire, United Kingdom), a vascular endothelial growth factor receptor and platelet-derived growth factor receptor inhibitor, demonstrated therapeutic potential in a prior phase I trial. We evaluated a phase II trial for efficacy. PATIENTS AND METHODS SWOG S0905 (ClinicalTrials.gov identifier: NCT01064648) randomly assigned cediranib or placebo with platinum-pemetrexed for six cycles followed by maintenance cediranib or placebo in unresectable chemotherapy-naïve patients with MPM of any histologic subtype. Primary end point was Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 progression-free survival (PFS). Secondary end points included overall survival, PFS by modified RECIST v1.1, response (modified RECIST and RECIST v1.1), disease control, and safety/toxicity. The trial was designed to detect a difference in RECIST v1.1 PFS at the one-sided 0.1 level using a stratified log-rank test. RESULTS Ninety-two eligible patients were enrolled (75% epithelioid and 25% biphasic or sarcomatoid). The cediranib arm had more grade 3 and 4 diarrhea, dehydration, hypertension, and weight loss. Cediranib improved PFS by RECIST v1.1 (hazard ratio, 0.71; 80% CI, 0.54 to 0.95; P =.062; 7.2 months v 5.6 months) and increased modified RECIST v1.1 response (50% v 20%; P =.006). By modified RECIST v1.1, cediranib numerically increased PFS (hazard ratio, 0.77; 80% CI, 0.59 to 1.02; P =.12; median, 6.9 months v 5.6 months). No significant difference in overall survival was observed. CONCLUSION The addition of cediranib to platinum-pemetrexed improved PFS by RECIST v1.1 and response rate by modified RECIST in patients with unresectable MPM. Whereas adding antiangiogenics to chemotherapy has been a successful strategy for some patients, the cediranib toxicity profile and small incremental survival benefit precludes additional development in MPM.
AB - PURPOSE Antiangiogenic agents combined with chemotherapy have efficacy in the treatment of unresectable malignant pleural mesothelioma (MPM). Cediranib (AstraZeneca, Cheshire, United Kingdom), a vascular endothelial growth factor receptor and platelet-derived growth factor receptor inhibitor, demonstrated therapeutic potential in a prior phase I trial. We evaluated a phase II trial for efficacy. PATIENTS AND METHODS SWOG S0905 (ClinicalTrials.gov identifier: NCT01064648) randomly assigned cediranib or placebo with platinum-pemetrexed for six cycles followed by maintenance cediranib or placebo in unresectable chemotherapy-naïve patients with MPM of any histologic subtype. Primary end point was Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 progression-free survival (PFS). Secondary end points included overall survival, PFS by modified RECIST v1.1, response (modified RECIST and RECIST v1.1), disease control, and safety/toxicity. The trial was designed to detect a difference in RECIST v1.1 PFS at the one-sided 0.1 level using a stratified log-rank test. RESULTS Ninety-two eligible patients were enrolled (75% epithelioid and 25% biphasic or sarcomatoid). The cediranib arm had more grade 3 and 4 diarrhea, dehydration, hypertension, and weight loss. Cediranib improved PFS by RECIST v1.1 (hazard ratio, 0.71; 80% CI, 0.54 to 0.95; P =.062; 7.2 months v 5.6 months) and increased modified RECIST v1.1 response (50% v 20%; P =.006). By modified RECIST v1.1, cediranib numerically increased PFS (hazard ratio, 0.77; 80% CI, 0.59 to 1.02; P =.12; median, 6.9 months v 5.6 months). No significant difference in overall survival was observed. CONCLUSION The addition of cediranib to platinum-pemetrexed improved PFS by RECIST v1.1 and response rate by modified RECIST in patients with unresectable MPM. Whereas adding antiangiogenics to chemotherapy has been a successful strategy for some patients, the cediranib toxicity profile and small incremental survival benefit precludes additional development in MPM.
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U2 - 10.1200/JCO.19.00269
DO - 10.1200/JCO.19.00269
M3 - Article
C2 - 31386610
AN - SCOPUS:85072716729
SN - 0732-183X
VL - 37
SP - 2537
EP - 2547
JO - Journal of Clinical Oncology
JF - Journal of Clinical Oncology
IS - 28
ER -