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 - 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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U2 - 10.1016/j.cllc.2020.01.006
DO - 10.1016/j.cllc.2020.01.006
M3 - Article
C2 - 32173247
AN - SCOPUS:85081894574
SN - 1525-7304
VL - 21
SP - 357-364.e7
JO - Clinical Lung Cancer
JF - Clinical Lung Cancer
IS - 4
ER -
