Efficacy, safety, and biomarker analysis of combined pd-l1 (Atezolizumab) and vegf (bevacizumab) blockade in advanced mesothelioma

Kanwal Raghav; Suyu Liu; Michael J. Overman; Anneleis F. Willett; Mark Knafl; Szu Chin Fu; Anais Malpica; Seema Prasad; Richard E. Royal; Christopher P. Scally; Paul F. Mansfield; Ignacio I. Wistuba; Andrew P. Futreal; Dipen M. Maru; Luisa M. Solis Soto; Edwin R. Parra Cuentas; Honglei Chen; Pamela Villalobos; Anuj Verma; Armeen Mahvash; Patrick Hwu; Patricia Cortazar; Edward McKenna; Cindy Yun; Shannon Dervin; Katja Schulze; Walter C. Darbonne; Ajaykumar C. Morani; Scott Kopetz; Keith F. Fournier; Scott E. Woodman; James C. Yao; Gauri R. Varadhachary; Daniel M. Halperin

doi:10.1158/2159-8290.CD-21-0331

Efficacy, safety, and biomarker analysis of combined pd-l1 (Atezolizumab) and vegf (bevacizumab) blockade in advanced mesothelioma

Kanwal Raghav, Suyu Liu, Michael J. Overman, Anneleis F. Willett, Mark Knafl, Szu Chin Fu, Anais Malpica, Seema Prasad, Richard E. Royal, Christopher P. Scally, Paul F. Mansfield, Ignacio I. Wistuba, Andrew P. Futreal, Dipen M. Maru, Luisa M. Solis Soto, Edwin R. Parra Cuentas, Honglei Chen, Pamela Villalobos, Anuj Verma, Armeen MahvashPatrick Hwu, Patricia Cortazar, Edward McKenna, Cindy Yun, Shannon Dervin, Katja Schulze, Walter C. Darbonne, Ajaykumar C. Morani, Scott Kopetz, Keith F. Fournier, Scott E. Woodman, James C. Yao, Gauri R. Varadhachary, Daniel M. Halperin

Research output: Contribution to journal › Article › peer-review

48 Scopus citations

Abstract

Malignant peritoneal mesothelioma (MPeM) is a rare but aggressive malignancy with limited treatment options. VEGF inhibition enhances efficacy of immune-checkpoint inhibitors by reworking the immunosuppressive tumor milieu. Efficacy and safety of com¬bined PD-L1 (atezolizumab) and VEGF (bevacizumab) blockade (AtezoBev) was assessed in 20 patients with advanced and unresectable MPeM with progression or intolerance to prior platinum-pemetrexed chemotherapy. The primary endpoint of confirmed objective response rate per RECISTvl.1 by independ¬ent radiology review was 40% [8/20; 95% confidence interval (CI), 19.1-64.0] with median response duration of 12.8 months. Six (75%) responses lasted for >10 months. Progression-free and overall survival at one year were 61% (95% CI, 35-80) and 85% (95% CI, 60-95), respectively. Responses occurred notwithstanding low tumor mutation burden and PD-L1 expression status. Baseline epithelial- mesenchymal transition gene expression correlated with therapeutic resistance/response (r = 0.80; P = 0.0010). AtezoBev showed promising and durable efficacy in patients with advanced MPeM with an acceptable safety profile, and these results address a grave unmet need for this orphan disease.

Original language	English (US)
Pages (from-to)	2738-2747
Number of pages	10
Journal	Cancer discovery
Volume	11
Issue number	11
DOIs	https://doi.org/10.1158/2159-8290.CD-21-0331
State	Published - Nov 2021

ASJC Scopus subject areas

Oncology

MD Anderson CCSG core facilities

Biostatistics Resource Group
Tissue Biospecimen and Pathology Resource
Flow Cytometry and Cellular Imaging Facility

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10.1158/2159-8290.CD-21-0331

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Raghav, K., Liu, S., Overman, M. J., Willett, A. F., Knafl, M., Fu, S. C., Malpica, A., Prasad, S., Royal, R. E., Scally, C. P., Mansfield, P. F., Wistuba, I. I., Futreal, A. P., Maru, D. M., Solis Soto, L. M., Parra Cuentas, E. R., Chen, H., Villalobos, P., Verma, A., ... Halperin, D. M. (2021). Efficacy, safety, and biomarker analysis of combined pd-l1 (Atezolizumab) and vegf (bevacizumab) blockade in advanced mesothelioma. Cancer discovery, 11(11), 2738-2747. https://doi.org/10.1158/2159-8290.CD-21-0331

Raghav, K , Liu, S , Overman, MJ, Willett, AF, Knafl, M, Fu, SC, Malpica, A, Prasad, S, Royal, RE, Scally, CP , Mansfield, PF , Wistuba, II , Futreal, AP , Maru, DM , Solis Soto, LM, Parra Cuentas, ER, Chen, H, Villalobos, P, Verma, A, Mahvash, A, Hwu, P, Cortazar, P, McKenna, E, Yun, C, Dervin, S, Schulze, K, Darbonne, WC, Morani, AC , Kopetz, S , Fournier, KF , Woodman, SE , Yao, JC, Varadhachary, GR & Halperin, DM 2021, 'Efficacy, safety, and biomarker analysis of combined pd-l1 (Atezolizumab) and vegf (bevacizumab) blockade in advanced mesothelioma', Cancer discovery, vol. 11, no. 11, pp. 2738-2747. https://doi.org/10.1158/2159-8290.CD-21-0331

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title = "Efficacy, safety, and biomarker analysis of combined pd-l1 (Atezolizumab) and vegf (bevacizumab) blockade in advanced mesothelioma",

abstract = "Malignant peritoneal mesothelioma (MPeM) is a rare but aggressive malignancy with limited treatment options. VEGF inhibition enhances efficacy of immune-checkpoint inhibitors by reworking the immunosuppressive tumor milieu. Efficacy and safety of com¬bined PD-L1 (atezolizumab) and VEGF (bevacizumab) blockade (AtezoBev) was assessed in 20 patients with advanced and unresectable MPeM with progression or intolerance to prior platinum-pemetrexed chemotherapy. The primary endpoint of confirmed objective response rate per RECISTvl.1 by independ¬ent radiology review was 40% [8/20; 95% confidence interval (CI), 19.1-64.0] with median response duration of 12.8 months. Six (75%) responses lasted for >10 months. Progression-free and overall survival at one year were 61% (95% CI, 35-80) and 85% (95% CI, 60-95), respectively. Responses occurred notwithstanding low tumor mutation burden and PD-L1 expression status. Baseline epithelial- mesenchymal transition gene expression correlated with therapeutic resistance/response (r = 0.80; P = 0.0010). AtezoBev showed promising and durable efficacy in patients with advanced MPeM with an acceptable safety profile, and these results address a grave unmet need for this orphan disease.",

author = "Kanwal Raghav and Suyu Liu and Overman, {Michael J.} and Willett, {Anneleis F.} and Mark Knafl and Fu, {Szu Chin} and Anais Malpica and Seema Prasad and Royal, {Richard E.} and Scally, {Christopher P.} and Mansfield, {Paul F.} and Wistuba, {Ignacio I.} and Futreal, {Andrew P.} and Maru, {Dipen M.} and {Solis Soto}, {Luisa M.} and {Parra Cuentas}, {Edwin R.} and Honglei Chen and Pamela Villalobos and Anuj Verma and Armeen Mahvash and Patrick Hwu and Patricia Cortazar and Edward McKenna and Cindy Yun and Shannon Dervin and Katja Schulze and Darbonne, {Walter C.} and Morani, {Ajaykumar C.} and Scott Kopetz and Fournier, {Keith F.} and Woodman, {Scott E.} and Yao, {James C.} and Varadhachary, {Gauri R.} and Halperin, {Daniel M.}",

note = "Publisher Copyright: {\textcopyright} 2021 American Association for Cancer Research.",

year = "2021",

month = nov,

doi = "10.1158/2159-8290.CD-21-0331",

language = "English (US)",

volume = "11",

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journal = "Cancer discovery",

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publisher = "American Association for Cancer Research Inc.",

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T1 - Efficacy, safety, and biomarker analysis of combined pd-l1 (Atezolizumab) and vegf (bevacizumab) blockade in advanced mesothelioma

AU - Raghav, Kanwal

AU - Liu, Suyu

AU - Overman, Michael J.

AU - Willett, Anneleis F.

AU - Knafl, Mark

AU - Fu, Szu Chin

AU - Malpica, Anais

AU - Prasad, Seema

AU - Royal, Richard E.

AU - Scally, Christopher P.

AU - Mansfield, Paul F.

AU - Wistuba, Ignacio I.

AU - Futreal, Andrew P.

AU - Maru, Dipen M.

AU - Solis Soto, Luisa M.

AU - Parra Cuentas, Edwin R.

AU - Chen, Honglei

AU - Villalobos, Pamela

AU - Verma, Anuj

AU - Mahvash, Armeen

AU - Hwu, Patrick

AU - Cortazar, Patricia

AU - McKenna, Edward

AU - Yun, Cindy

AU - Dervin, Shannon

AU - Schulze, Katja

AU - Darbonne, Walter C.

AU - Morani, Ajaykumar C.

AU - Kopetz, Scott

AU - Fournier, Keith F.

AU - Woodman, Scott E.

AU - Yao, James C.

AU - Varadhachary, Gauri R.

AU - Halperin, Daniel M.

PY - 2021/11

Y1 - 2021/11

N2 - Malignant peritoneal mesothelioma (MPeM) is a rare but aggressive malignancy with limited treatment options. VEGF inhibition enhances efficacy of immune-checkpoint inhibitors by reworking the immunosuppressive tumor milieu. Efficacy and safety of com¬bined PD-L1 (atezolizumab) and VEGF (bevacizumab) blockade (AtezoBev) was assessed in 20 patients with advanced and unresectable MPeM with progression or intolerance to prior platinum-pemetrexed chemotherapy. The primary endpoint of confirmed objective response rate per RECISTvl.1 by independ¬ent radiology review was 40% [8/20; 95% confidence interval (CI), 19.1-64.0] with median response duration of 12.8 months. Six (75%) responses lasted for >10 months. Progression-free and overall survival at one year were 61% (95% CI, 35-80) and 85% (95% CI, 60-95), respectively. Responses occurred notwithstanding low tumor mutation burden and PD-L1 expression status. Baseline epithelial- mesenchymal transition gene expression correlated with therapeutic resistance/response (r = 0.80; P = 0.0010). AtezoBev showed promising and durable efficacy in patients with advanced MPeM with an acceptable safety profile, and these results address a grave unmet need for this orphan disease.

AB - Malignant peritoneal mesothelioma (MPeM) is a rare but aggressive malignancy with limited treatment options. VEGF inhibition enhances efficacy of immune-checkpoint inhibitors by reworking the immunosuppressive tumor milieu. Efficacy and safety of com¬bined PD-L1 (atezolizumab) and VEGF (bevacizumab) blockade (AtezoBev) was assessed in 20 patients with advanced and unresectable MPeM with progression or intolerance to prior platinum-pemetrexed chemotherapy. The primary endpoint of confirmed objective response rate per RECISTvl.1 by independ¬ent radiology review was 40% [8/20; 95% confidence interval (CI), 19.1-64.0] with median response duration of 12.8 months. Six (75%) responses lasted for >10 months. Progression-free and overall survival at one year were 61% (95% CI, 35-80) and 85% (95% CI, 60-95), respectively. Responses occurred notwithstanding low tumor mutation burden and PD-L1 expression status. Baseline epithelial- mesenchymal transition gene expression correlated with therapeutic resistance/response (r = 0.80; P = 0.0010). AtezoBev showed promising and durable efficacy in patients with advanced MPeM with an acceptable safety profile, and these results address a grave unmet need for this orphan disease.

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Efficacy, safety, and biomarker analysis of combined pd-l1 (Atezolizumab) and vegf (bevacizumab) blockade in advanced mesothelioma

Abstract

ASJC Scopus subject areas

MD Anderson CCSG core facilities

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