Adaptive Dosing of Nivolumab plus lpilimumab Immunotherapy Based Upon Early, Interim Radiographic Assessment in Advanced Melanoma (The ADAPT-IT Study)

被引:41
作者
Postow, Michael A. [1 ,2 ]
Goldman, Debra A. [1 ]
Shoushtari, Alexander N. [1 ,2 ]
Warner, Allison Betof [1 ,2 ]
Callahan, Margaret K. [1 ,2 ]
Momtaz, Parisa [1 ,2 ]
Smithy, James W. [1 ,2 ]
Naito, Ellesa [1 ]
Cugliari, Marina K. [1 ]
Raber, Vladislav [1 ]
Eton, Omar [3 ]
Nair, Suresh G. [4 ]
Panageas, Katherine S. [1 ]
Wolchok, Jedd D. [1 ,2 ]
Chapman, Paul B. [1 ,2 ]
机构
[1] Mem Sloan Kettering Canc Ctr, 1275 York Ave, New York, NY 10021 USA
[2] Weill Cornell Med Coll, New York, NY USA
[3] Hartford Healthcare, Hartford, CT USA
[4] Lehigh Valley Hlth Network, Allentown, PA USA
基金
美国国家卫生研究院;
关键词
IPILIMUMAB;
D O I
10.1200/JCO.21.01570
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
PURPOSE Nivolumab + ipilimumab (nivo + ipi) is highly efficacious but has high toxicity. Standard treatment in advanced melanoma is four doses of nivo + ipi followed by nivo alone. Whether four doses of nivo + ipi are needed is unclear. METHODS The Adaptively Dosed ImmunoTherapy Trial (ADAPT-IT) study (NCT03122522) is a multicenter, single-arm phase II clinical trial. Patients received two doses of nivo (1 mg/kg) + ipi (3 mg/kg) followed by a computed tomography scan at week 6. Patients without new lesions or index lesion tumor growth of > 4% had protocol-defined early favorable antitumor effect (FATE) and ceased nivo + ipi, transitioning to nivo monotherapy. Patients without FATE at week 6 received the standard third and fourth doses of nivo + ipi followed by nivo monotherapy. The primary end point was response rate by RECIST 1.1 at week 12. Secondary end points included additional efficacy assessments and safety. RESULTS Sixty patients were enrolled; 41 patients (68%) had FATE at week 6 and met criteria for stopping nivo + ipi. Best overall response rates by RECIST at week 12 or any time afterward were 48% (95% CI, 35 to 62) and 58% (95% CI, 45 to 71), respectively. With a median follow-up of 25 months, the estimated 18-month progression-free survival and overall survival are 52% and 80%, respectively. Fifty seven percent of patients had grade 3-5 treatment-related toxicity. CONCLUSION The efficacy and toxicity of standard four dose nivo + ipi induction therapy in melanoma is likely driven by the first two doses. An interim computed tomography scan after two doses guided cessation of combination dosing and identified almost all responders. Longer follow-up and further study are needed to fully understand the implications of a shortened induction course of nivo + ipi.
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页码:1059 / +
页数:17
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