Phase II Trial of Carfilzomib Plus Irinotecan in Patients With Small-cell Lung Cancer Who Have Progressed on Prior Platinum-based Chemotherapy

Susanne M. Arnold; Kari Chansky; Maria Q. Baggstrom; Michael A. Thompson; Rachel E. Sanborn; John L. Villano; Saiama N. Waqar; John Hamm; Markos Leggas; Maurice Willis; Joseph Rosales; John J. Crowley

doi:10.1016/j.cllc.2020.01.006

Phase II Trial of Carfilzomib Plus Irinotecan in Patients With Small-cell Lung Cancer Who Have Progressed on Prior Platinum-based Chemotherapy

Susanne M. Arnold, Kari Chansky, Maria Q. Baggstrom, Michael A. Thompson, Rachel E. Sanborn, John L. Villano, Saiama N. Waqar, John Hamm, Markos Leggas, Maurice Willis, Joseph Rosales, John J. Crowley

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

4 Scopus citations

Abstract

Introduction: The purpose of this study was to evaluate the efficacy and tolerability of carfilzomib plus irinotecan (C/I) in patients with relapsed small-cell lung cancer (SCLC). Patients and Methods: Patients with SCLC who progressed after 1 platinum-containing regimen for recurrent or metastatic disease were eligible. Patients were stratified as: sensitive (SS) (progressive disease > 90 days after chemotherapy) or refractory (RS) (progressive disease 30 to 90 days after chemotherapy) and received up to 6 cycles of C/I; imaging was performed every 2 cycles. The primary endpoint was 6-month overall survival (OS). Results: All 62 patients enrolled were evaluable for efficacy and adverse events. 6-month OS was 59% in the platinum SS and 54% in the platinum RS. The overall response rate was 21.6% (2.7% complete response, 18.9% partial response) in SS (n = 37) and 12.5% (all partial response) in RS (n = 25). The disease control rate was 68% (SS) and 56% (RS). Progression-free survival and OS were 3.6 months (95% confidence interval [CI], 2.6-4.6 months) and 6.9 months (95% CI, 4.3-12.3 months) in SS, and 3.3 months (95% CI, 1.8-3.9 months) and 6.8 months (95% CI, 4.1-11 months) in RS. Twenty-nine (47%) patients experienced ≥ grade 3 adverse events; 8 (12.9%) subjects had grade 4 toxicities. Three treatment-related deaths occurred: myocardial infarction (possible), lung infection (possible), and sepsis (probable). Conclusion: In patients with relapsed SCLC, C/I was effective in the treatment of SS and RS. With 4.8% grade 5 toxicity, C/I is a viable option for relapsed patients with SCLC with performance status 0 to 1, particularly in platinum-resistant patients, or subjects who cannot receive immunotherapy. This study's objective was to evaluate the efficacy and tolerability of carfilzomib plus irinotecan in patients with relapsed small-cell lung cancer. This was a single-arm phase II trial of 62 patients with small-cell lung cancer who progressed after 1 platinum-containing regimen for recurrent or metastatic disease. The 6-month overall survival was 59% in platinum-sensitive patients and 54% in platinum-refractory patients.

Original language	English
Pages (from-to)	357-364.e7
Journal	Clinical Lung Cancer
Volume	21
Issue number	4
DOIs	https://doi.org/10.1016/j.cllc.2020.01.006
State	Published - Jul 2020

Bibliographical note

Funding Information:
The authors wish to thank Amy Stoll-D’Astice, Grace Powell, and the staff of the Cancer Research and Biostatistics for their assistance with this study. This investigation was supported by Cancer Research and Biostatistics and Amgen Pharmaceuticals .

Funding Information:
All authors disclose research funding received from Onyx Pharmaceuticals, a subsidiary of Amgen. There are no other potential conflicts of interest for any authors.The authors wish to thank Amy Stoll-D'Astice, Grace Powell, and the staff of the Cancer Research and Biostatistics for their assistance with this study. This investigation was supported by Cancer Research and Biostatistics and Amgen Pharmaceuticals.

Publisher Copyright:
© 2020 Elsevier Inc.

Keywords

Camptothecin combination
Chemotherapy
Proteasome inhibition
Relapse
Small cell lung cancer

ASJC Scopus subject areas

Oncology
Pulmonary and Respiratory Medicine
Cancer Research

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.cllc.2020.01.006

Cite this

Arnold, S. M., Chansky, K., Baggstrom, M. Q., Thompson, M. A., Sanborn, R. E., Villano, J. L., Waqar, S. N., Hamm, J., Leggas, M., Willis, M., Rosales, J., & Crowley, J. J. (2020). Phase II Trial of Carfilzomib Plus Irinotecan in Patients With Small-cell Lung Cancer Who Have Progressed on Prior Platinum-based Chemotherapy. Clinical Lung Cancer, 21(4), 357-364.e7. https://doi.org/10.1016/j.cllc.2020.01.006

@article{ff6f2ce426a7483ab94ea8c2e628fc11,

title = "Phase II Trial of Carfilzomib Plus Irinotecan in Patients With Small-cell Lung Cancer Who Have Progressed on Prior Platinum-based Chemotherapy",

abstract = "Introduction: The purpose of this study was to evaluate the efficacy and tolerability of carfilzomib plus irinotecan (C/I) in patients with relapsed small-cell lung cancer (SCLC). Patients and Methods: Patients with SCLC who progressed after 1 platinum-containing regimen for recurrent or metastatic disease were eligible. Patients were stratified as: sensitive (SS) (progressive disease > 90 days after chemotherapy) or refractory (RS) (progressive disease 30 to 90 days after chemotherapy) and received up to 6 cycles of C/I; imaging was performed every 2 cycles. The primary endpoint was 6-month overall survival (OS). Results: All 62 patients enrolled were evaluable for efficacy and adverse events. 6-month OS was 59% in the platinum SS and 54% in the platinum RS. The overall response rate was 21.6% (2.7% complete response, 18.9% partial response) in SS (n = 37) and 12.5% (all partial response) in RS (n = 25). The disease control rate was 68% (SS) and 56% (RS). Progression-free survival and OS were 3.6 months (95% confidence interval [CI], 2.6-4.6 months) and 6.9 months (95% CI, 4.3-12.3 months) in SS, and 3.3 months (95% CI, 1.8-3.9 months) and 6.8 months (95% CI, 4.1-11 months) in RS. Twenty-nine (47%) patients experienced ≥ grade 3 adverse events; 8 (12.9%) subjects had grade 4 toxicities. Three treatment-related deaths occurred: myocardial infarction (possible), lung infection (possible), and sepsis (probable). Conclusion: In patients with relapsed SCLC, C/I was effective in the treatment of SS and RS. With 4.8% grade 5 toxicity, C/I is a viable option for relapsed patients with SCLC with performance status 0 to 1, particularly in platinum-resistant patients, or subjects who cannot receive immunotherapy. This study's objective was to evaluate the efficacy and tolerability of carfilzomib plus irinotecan in patients with relapsed small-cell lung cancer. This was a single-arm phase II trial of 62 patients with small-cell lung cancer who progressed after 1 platinum-containing regimen for recurrent or metastatic disease. The 6-month overall survival was 59% in platinum-sensitive patients and 54% in platinum-refractory patients.",

keywords = "Camptothecin combination, Chemotherapy, Proteasome inhibition, Relapse, Small cell lung cancer",

author = "Arnold, {Susanne M.} and Kari Chansky and Baggstrom, {Maria Q.} and Thompson, {Michael A.} and Sanborn, {Rachel E.} and Villano, {John L.} and Waqar, {Saiama N.} and John Hamm and Markos Leggas and Maurice Willis and Joseph Rosales and Crowley, {John J.}",

note = "Funding Information: The authors wish to thank Amy Stoll-D{\textquoteright}Astice, Grace Powell, and the staff of the Cancer Research and Biostatistics for their assistance with this study. This investigation was supported by Cancer Research and Biostatistics and Amgen Pharmaceuticals . Funding Information: All authors disclose research funding received from Onyx Pharmaceuticals, a subsidiary of Amgen. There are no other potential conflicts of interest for any authors.The authors wish to thank Amy Stoll-D'Astice, Grace Powell, and the staff of the Cancer Research and Biostatistics for their assistance with this study. This investigation was supported by Cancer Research and Biostatistics and Amgen Pharmaceuticals. Publisher Copyright: {\textcopyright} 2020 Elsevier Inc.",

year = "2020",

month = jul,

doi = "10.1016/j.cllc.2020.01.006",

language = "English",

volume = "21",

pages = "357--364.e7",

number = "4",

}

Arnold, SM, Chansky, K, Baggstrom, MQ, Thompson, MA, Sanborn, RE, Villano, JL, Waqar, SN, Hamm, J, Leggas, M, Willis, M, Rosales, J & Crowley, JJ 2020, 'Phase II Trial of Carfilzomib Plus Irinotecan in Patients With Small-cell Lung Cancer Who Have Progressed on Prior Platinum-based Chemotherapy', Clinical Lung Cancer, vol. 21, no. 4, pp. 357-364.e7. https://doi.org/10.1016/j.cllc.2020.01.006

TY - JOUR

T1 - Phase II Trial of Carfilzomib Plus Irinotecan in Patients With Small-cell Lung Cancer Who Have Progressed on Prior Platinum-based Chemotherapy

AU - Arnold, Susanne M.

AU - Chansky, Kari

AU - Baggstrom, Maria Q.

AU - Thompson, Michael A.

AU - Sanborn, Rachel E.

AU - Villano, John L.

AU - Waqar, Saiama N.

AU - Hamm, John

AU - Leggas, Markos

AU - Willis, Maurice

AU - Rosales, Joseph

AU - Crowley, John J.

N1 - Funding Information: The authors wish to thank Amy Stoll-D’Astice, Grace Powell, and the staff of the Cancer Research and Biostatistics for their assistance with this study. This investigation was supported by Cancer Research and Biostatistics and Amgen Pharmaceuticals . Funding Information: All authors disclose research funding received from Onyx Pharmaceuticals, a subsidiary of Amgen. There are no other potential conflicts of interest for any authors.The authors wish to thank Amy Stoll-D'Astice, Grace Powell, and the staff of the Cancer Research and Biostatistics for their assistance with this study. This investigation was supported by Cancer Research and Biostatistics and Amgen Pharmaceuticals. Publisher Copyright: © 2020 Elsevier Inc.

PY - 2020/7

Y1 - 2020/7

N2 - Introduction: The purpose of this study was to evaluate the efficacy and tolerability of carfilzomib plus irinotecan (C/I) in patients with relapsed small-cell lung cancer (SCLC). Patients and Methods: Patients with SCLC who progressed after 1 platinum-containing regimen for recurrent or metastatic disease were eligible. Patients were stratified as: sensitive (SS) (progressive disease > 90 days after chemotherapy) or refractory (RS) (progressive disease 30 to 90 days after chemotherapy) and received up to 6 cycles of C/I; imaging was performed every 2 cycles. The primary endpoint was 6-month overall survival (OS). Results: All 62 patients enrolled were evaluable for efficacy and adverse events. 6-month OS was 59% in the platinum SS and 54% in the platinum RS. The overall response rate was 21.6% (2.7% complete response, 18.9% partial response) in SS (n = 37) and 12.5% (all partial response) in RS (n = 25). The disease control rate was 68% (SS) and 56% (RS). Progression-free survival and OS were 3.6 months (95% confidence interval [CI], 2.6-4.6 months) and 6.9 months (95% CI, 4.3-12.3 months) in SS, and 3.3 months (95% CI, 1.8-3.9 months) and 6.8 months (95% CI, 4.1-11 months) in RS. Twenty-nine (47%) patients experienced ≥ grade 3 adverse events; 8 (12.9%) subjects had grade 4 toxicities. Three treatment-related deaths occurred: myocardial infarction (possible), lung infection (possible), and sepsis (probable). Conclusion: In patients with relapsed SCLC, C/I was effective in the treatment of SS and RS. With 4.8% grade 5 toxicity, C/I is a viable option for relapsed patients with SCLC with performance status 0 to 1, particularly in platinum-resistant patients, or subjects who cannot receive immunotherapy. This study's objective was to evaluate the efficacy and tolerability of carfilzomib plus irinotecan in patients with relapsed small-cell lung cancer. This was a single-arm phase II trial of 62 patients with small-cell lung cancer who progressed after 1 platinum-containing regimen for recurrent or metastatic disease. The 6-month overall survival was 59% in platinum-sensitive patients and 54% in platinum-refractory patients.

AB - Introduction: The purpose of this study was to evaluate the efficacy and tolerability of carfilzomib plus irinotecan (C/I) in patients with relapsed small-cell lung cancer (SCLC). Patients and Methods: Patients with SCLC who progressed after 1 platinum-containing regimen for recurrent or metastatic disease were eligible. Patients were stratified as: sensitive (SS) (progressive disease > 90 days after chemotherapy) or refractory (RS) (progressive disease 30 to 90 days after chemotherapy) and received up to 6 cycles of C/I; imaging was performed every 2 cycles. The primary endpoint was 6-month overall survival (OS). Results: All 62 patients enrolled were evaluable for efficacy and adverse events. 6-month OS was 59% in the platinum SS and 54% in the platinum RS. The overall response rate was 21.6% (2.7% complete response, 18.9% partial response) in SS (n = 37) and 12.5% (all partial response) in RS (n = 25). The disease control rate was 68% (SS) and 56% (RS). Progression-free survival and OS were 3.6 months (95% confidence interval [CI], 2.6-4.6 months) and 6.9 months (95% CI, 4.3-12.3 months) in SS, and 3.3 months (95% CI, 1.8-3.9 months) and 6.8 months (95% CI, 4.1-11 months) in RS. Twenty-nine (47%) patients experienced ≥ grade 3 adverse events; 8 (12.9%) subjects had grade 4 toxicities. Three treatment-related deaths occurred: myocardial infarction (possible), lung infection (possible), and sepsis (probable). Conclusion: In patients with relapsed SCLC, C/I was effective in the treatment of SS and RS. With 4.8% grade 5 toxicity, C/I is a viable option for relapsed patients with SCLC with performance status 0 to 1, particularly in platinum-resistant patients, or subjects who cannot receive immunotherapy. This study's objective was to evaluate the efficacy and tolerability of carfilzomib plus irinotecan in patients with relapsed small-cell lung cancer. This was a single-arm phase II trial of 62 patients with small-cell lung cancer who progressed after 1 platinum-containing regimen for recurrent or metastatic disease. The 6-month overall survival was 59% in platinum-sensitive patients and 54% in platinum-refractory patients.

KW - Camptothecin combination

KW - Chemotherapy

KW - Proteasome inhibition

KW - Relapse

KW - Small cell lung cancer

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Phase II Trial of Carfilzomib Plus Irinotecan in Patients With Small-cell Lung Cancer Who Have Progressed on Prior Platinum-based Chemotherapy

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

UN SDGs

Access to Document

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