TY - JOUR
T1 - Phase II Clinical Trial of Axitinib and Avelumab in Patients With Recurrent/Metastatic Adenoid Cystic Carcinoma
AU - Ferrarotto, Renata
AU - Sousa, Luana G.
AU - Feng, Lei
AU - Mott, Frank
AU - Blumenschein, George
AU - Altan, Mehmet
AU - Bell, Diana
AU - Bonini, Flavia
AU - Li, Kaiyi
AU - Marques-Piubelli, Mario L.
AU - Dal Lago, Eduardo A.
AU - Johnson, Jason J.
AU - Mitani, Yoshitsugu
AU - Godoy, Myrna
AU - Lee, Anna
AU - Kupferman, Michael
AU - Hanna, Ehab
AU - Glisson, Bonnie S.
AU - Elamin, Yasir
AU - El-Naggar, Adel
N1 - Publisher Copyright:
© American Society of Clinical Oncology.
PY - 2023/5/20
Y1 - 2023/5/20
N2 - PURPOSEWe conducted a phase II trial evaluating the efficacy of VEGFR inhibitor axitinib and PD-L1 inhibitor avelumab in patients with recurrent/metastatic adenoid cystic carcinoma (R/M ACC).PATIENTS AND METHODSEligible patients had R/M ACC with progression within 6 months before enrollment. Treatment consisted of axitinib and avelumab. The primary end point was objective response rate (ORR) per RECIST 1.1; secondary end points included progression-free survival (PFS), overall survival (OS), and toxicity. Simon's optimal two-stage design tested the null hypothesis of ORR ≤5% versus ORR ≥20% at 6 months; %4 responses in 29 patients would reject the null hypothesis.RESULTSForty patients enrolled from July 2019 to June 2021; 28 were evaluable for efficacy (six screen failures; six evaluable for safety only). The confirmed ORR was 18% (95% CI, 6.1 to 36.9); there was one unconfirmed partial response (PR). Two patients achieved PR after 6 months; thus, the ORR at 6 months was 14%. The median follow-up time for surviving patients was 22 months (95% CI, 16.6 to 39.1 months). The median PFS was 7.3 months (95% CI, 3.7 to 11.2 months), 6-month PFS rate was 57% (95% CI, 41 to 78), and median OS was 16.6 months (95% CI, 12.4 to not reached months). Most common treatment-related adverse events (TRAEs) included fatigue (62%), hypertension (32%), and diarrhea (32%). Ten (29%) patients had serious TRAEs, all grade 3; four patients (12%) discontinued avelumab, and nine patients (26%) underwent axitinib dose reduction.CONCLUSIONThe study reached its primary end point with %4 PRs in 28 evaluable patients (confirmed ORR of 18%). The potential added benefit of avelumab to axitinib in ACC requires further investigation.
AB - PURPOSEWe conducted a phase II trial evaluating the efficacy of VEGFR inhibitor axitinib and PD-L1 inhibitor avelumab in patients with recurrent/metastatic adenoid cystic carcinoma (R/M ACC).PATIENTS AND METHODSEligible patients had R/M ACC with progression within 6 months before enrollment. Treatment consisted of axitinib and avelumab. The primary end point was objective response rate (ORR) per RECIST 1.1; secondary end points included progression-free survival (PFS), overall survival (OS), and toxicity. Simon's optimal two-stage design tested the null hypothesis of ORR ≤5% versus ORR ≥20% at 6 months; %4 responses in 29 patients would reject the null hypothesis.RESULTSForty patients enrolled from July 2019 to June 2021; 28 were evaluable for efficacy (six screen failures; six evaluable for safety only). The confirmed ORR was 18% (95% CI, 6.1 to 36.9); there was one unconfirmed partial response (PR). Two patients achieved PR after 6 months; thus, the ORR at 6 months was 14%. The median follow-up time for surviving patients was 22 months (95% CI, 16.6 to 39.1 months). The median PFS was 7.3 months (95% CI, 3.7 to 11.2 months), 6-month PFS rate was 57% (95% CI, 41 to 78), and median OS was 16.6 months (95% CI, 12.4 to not reached months). Most common treatment-related adverse events (TRAEs) included fatigue (62%), hypertension (32%), and diarrhea (32%). Ten (29%) patients had serious TRAEs, all grade 3; four patients (12%) discontinued avelumab, and nine patients (26%) underwent axitinib dose reduction.CONCLUSIONThe study reached its primary end point with %4 PRs in 28 evaluable patients (confirmed ORR of 18%). The potential added benefit of avelumab to axitinib in ACC requires further investigation.
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U2 - 10.1200/JCO.22.02221
DO - 10.1200/JCO.22.02221
M3 - Article
C2 - 36898078
AN - SCOPUS:85159772051
SN - 0732-183X
VL - 41
SP - 2843
EP - 2851
JO - Journal of Clinical Oncology
JF - Journal of Clinical Oncology
IS - 15
ER -