Nivolumab in Metastatic Adrenocortical Carcinoma: Results of a Phase 2 Trial

Benedito A. Carneiro, Bhavana Konda, Rubens B. Costa, Ricardo L.B. Costa, Vinay Sagar, Demirkan B. Gursel, Lawrence S. Kirschner, Young Kwang Chae, Sarki A. Abdulkadir, Alfred Rademaker, Devalingam Mahalingam, Manisha H. Shah, Francis J. Giles

Research output: Contribution to journalArticle

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Abstract

CONTEXT: Systemic treatment of metastatic adrenocortical carcinoma (ACC) remains limited to chemotherapy and mitotane. Preliminary evidence suggesting that antitumor immune responses can be elicited in ACC has fostered interest in checkpoint inhibitors such as anti-PD-1 nivolumab. OBJECTIVE: The primary endpoint was objective response rate according to the response evaluation criteria in solid tumors. Secondary endpoints were progression-free survival (PFS), overall survival, and safety. DESIGN: Single-arm, multicenter, phase 2 clinical trial with two-stage design. SETTING: Comprehensive cancer center. PATIENTS: Ten adult patients with metastatic ACC previously treated with platinum-based chemotherapy and/or mitotane as well as patients who declined front-line chemotherapy. INTERVENTION: Nivolumab (240 mg) IV every 2 weeks. RESULTS: Ten patients with metastatic ACC were enrolled between March and December 2016. The median number of doses of nivolumab administered was two. Three patients only received one treatment [one died of disease progression, one discontinued due to adverse events (AEs), one withdrew after beginning treatment]. The median PFS was 1.8 months. The median follow-up was 4.5 months (range, 0.1 to 25.6 months). Two patients had stable disease for a duration of 48 and 11 weeks, respectively. One patient had an unconfirmed partial response but discontinued the study due to an AE. Most AEs were grade 1/2. The most common grade 3/4 treatment-related AEs were aspartate aminotransferase and alanine aminotransferase elevations, mucositis, and odynophagia. CONCLUSION: Nivolumab demonstrated modest antitumor activity in patients with advanced ACC. The nivolumab safety profile was consistent with previous clinical experience without any unexpected AEs in this population.

Original languageEnglish (US)
Pages (from-to)6193-6200
Number of pages8
JournalThe Journal of clinical endocrinology and metabolism
Volume104
Issue number12
DOIs
StatePublished - Dec 1 2019

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Adrenocortical Carcinoma
Chemotherapy
Mitotane
Drug Therapy
Disease-Free Survival
Aspartate Aminotransferases
Platinum
Alanine Transaminase
Safety
Mucositis
Tumors
Therapeutics
nivolumab
Disease Progression
Clinical Trials
Survival

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Endocrinology
  • Clinical Biochemistry
  • Biochemistry, medical

Cite this

Carneiro, Benedito A. ; Konda, Bhavana ; Costa, Rubens B. ; Costa, Ricardo L.B. ; Sagar, Vinay ; Gursel, Demirkan B. ; Kirschner, Lawrence S. ; Chae, Young Kwang ; Abdulkadir, Sarki A. ; Rademaker, Alfred ; Mahalingam, Devalingam ; Shah, Manisha H. ; Giles, Francis J. / Nivolumab in Metastatic Adrenocortical Carcinoma : Results of a Phase 2 Trial. In: The Journal of clinical endocrinology and metabolism. 2019 ; Vol. 104, No. 12. pp. 6193-6200.
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abstract = "CONTEXT: Systemic treatment of metastatic adrenocortical carcinoma (ACC) remains limited to chemotherapy and mitotane. Preliminary evidence suggesting that antitumor immune responses can be elicited in ACC has fostered interest in checkpoint inhibitors such as anti-PD-1 nivolumab. OBJECTIVE: The primary endpoint was objective response rate according to the response evaluation criteria in solid tumors. Secondary endpoints were progression-free survival (PFS), overall survival, and safety. DESIGN: Single-arm, multicenter, phase 2 clinical trial with two-stage design. SETTING: Comprehensive cancer center. PATIENTS: Ten adult patients with metastatic ACC previously treated with platinum-based chemotherapy and/or mitotane as well as patients who declined front-line chemotherapy. INTERVENTION: Nivolumab (240 mg) IV every 2 weeks. RESULTS: Ten patients with metastatic ACC were enrolled between March and December 2016. The median number of doses of nivolumab administered was two. Three patients only received one treatment [one died of disease progression, one discontinued due to adverse events (AEs), one withdrew after beginning treatment]. The median PFS was 1.8 months. The median follow-up was 4.5 months (range, 0.1 to 25.6 months). Two patients had stable disease for a duration of 48 and 11 weeks, respectively. One patient had an unconfirmed partial response but discontinued the study due to an AE. Most AEs were grade 1/2. The most common grade 3/4 treatment-related AEs were aspartate aminotransferase and alanine aminotransferase elevations, mucositis, and odynophagia. CONCLUSION: Nivolumab demonstrated modest antitumor activity in patients with advanced ACC. The nivolumab safety profile was consistent with previous clinical experience without any unexpected AEs in this population.",
author = "Carneiro, {Benedito A.} and Bhavana Konda and Costa, {Rubens B.} and Costa, {Ricardo L.B.} and Vinay Sagar and Gursel, {Demirkan B.} and Kirschner, {Lawrence S.} and Chae, {Young Kwang} and Abdulkadir, {Sarki A.} and Alfred Rademaker and Devalingam Mahalingam and Shah, {Manisha H.} and Giles, {Francis J.}",
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Carneiro, BA, Konda, B, Costa, RB, Costa, RLB, Sagar, V, Gursel, DB, Kirschner, LS, Chae, YK, Abdulkadir, SA, Rademaker, A, Mahalingam, D, Shah, MH & Giles, FJ 2019, 'Nivolumab in Metastatic Adrenocortical Carcinoma: Results of a Phase 2 Trial', The Journal of clinical endocrinology and metabolism, vol. 104, no. 12, pp. 6193-6200. https://doi.org/10.1210/jc.2019-00600

Nivolumab in Metastatic Adrenocortical Carcinoma : Results of a Phase 2 Trial. / Carneiro, Benedito A.; Konda, Bhavana; Costa, Rubens B.; Costa, Ricardo L.B.; Sagar, Vinay; Gursel, Demirkan B.; Kirschner, Lawrence S.; Chae, Young Kwang; Abdulkadir, Sarki A.; Rademaker, Alfred; Mahalingam, Devalingam; Shah, Manisha H.; Giles, Francis J.

In: The Journal of clinical endocrinology and metabolism, Vol. 104, No. 12, 01.12.2019, p. 6193-6200.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Nivolumab in Metastatic Adrenocortical Carcinoma

T2 - Results of a Phase 2 Trial

AU - Carneiro, Benedito A.

AU - Konda, Bhavana

AU - Costa, Rubens B.

AU - Costa, Ricardo L.B.

AU - Sagar, Vinay

AU - Gursel, Demirkan B.

AU - Kirschner, Lawrence S.

AU - Chae, Young Kwang

AU - Abdulkadir, Sarki A.

AU - Rademaker, Alfred

AU - Mahalingam, Devalingam

AU - Shah, Manisha H.

AU - Giles, Francis J.

PY - 2019/12/1

Y1 - 2019/12/1

N2 - CONTEXT: Systemic treatment of metastatic adrenocortical carcinoma (ACC) remains limited to chemotherapy and mitotane. Preliminary evidence suggesting that antitumor immune responses can be elicited in ACC has fostered interest in checkpoint inhibitors such as anti-PD-1 nivolumab. OBJECTIVE: The primary endpoint was objective response rate according to the response evaluation criteria in solid tumors. Secondary endpoints were progression-free survival (PFS), overall survival, and safety. DESIGN: Single-arm, multicenter, phase 2 clinical trial with two-stage design. SETTING: Comprehensive cancer center. PATIENTS: Ten adult patients with metastatic ACC previously treated with platinum-based chemotherapy and/or mitotane as well as patients who declined front-line chemotherapy. INTERVENTION: Nivolumab (240 mg) IV every 2 weeks. RESULTS: Ten patients with metastatic ACC were enrolled between March and December 2016. The median number of doses of nivolumab administered was two. Three patients only received one treatment [one died of disease progression, one discontinued due to adverse events (AEs), one withdrew after beginning treatment]. The median PFS was 1.8 months. The median follow-up was 4.5 months (range, 0.1 to 25.6 months). Two patients had stable disease for a duration of 48 and 11 weeks, respectively. One patient had an unconfirmed partial response but discontinued the study due to an AE. Most AEs were grade 1/2. The most common grade 3/4 treatment-related AEs were aspartate aminotransferase and alanine aminotransferase elevations, mucositis, and odynophagia. CONCLUSION: Nivolumab demonstrated modest antitumor activity in patients with advanced ACC. The nivolumab safety profile was consistent with previous clinical experience without any unexpected AEs in this population.

AB - CONTEXT: Systemic treatment of metastatic adrenocortical carcinoma (ACC) remains limited to chemotherapy and mitotane. Preliminary evidence suggesting that antitumor immune responses can be elicited in ACC has fostered interest in checkpoint inhibitors such as anti-PD-1 nivolumab. OBJECTIVE: The primary endpoint was objective response rate according to the response evaluation criteria in solid tumors. Secondary endpoints were progression-free survival (PFS), overall survival, and safety. DESIGN: Single-arm, multicenter, phase 2 clinical trial with two-stage design. SETTING: Comprehensive cancer center. PATIENTS: Ten adult patients with metastatic ACC previously treated with platinum-based chemotherapy and/or mitotane as well as patients who declined front-line chemotherapy. INTERVENTION: Nivolumab (240 mg) IV every 2 weeks. RESULTS: Ten patients with metastatic ACC were enrolled between March and December 2016. The median number of doses of nivolumab administered was two. Three patients only received one treatment [one died of disease progression, one discontinued due to adverse events (AEs), one withdrew after beginning treatment]. The median PFS was 1.8 months. The median follow-up was 4.5 months (range, 0.1 to 25.6 months). Two patients had stable disease for a duration of 48 and 11 weeks, respectively. One patient had an unconfirmed partial response but discontinued the study due to an AE. Most AEs were grade 1/2. The most common grade 3/4 treatment-related AEs were aspartate aminotransferase and alanine aminotransferase elevations, mucositis, and odynophagia. CONCLUSION: Nivolumab demonstrated modest antitumor activity in patients with advanced ACC. The nivolumab safety profile was consistent with previous clinical experience without any unexpected AEs in this population.

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