Nivolumab for Patients With Advanced Melanoma Treated Beyond Progression: Analysis of 2 Phase 3 Clinical Trials

Long, Georgina V., Weber, Jeffrey S., Larkin, James, Atkinson, Victoria, Grob, Jean-Jacques, Schadendorf, Dirk, Dummer, Reinhard, Robert, Caroline, Márquez-Rodas, Ivan, McNeil, Catriona, Schmidt, Henrik, Briscoe, Karen, Baurain, Jean-François, Hodi, F Stephen and Wolchok, Jedd D. (2017) Nivolumab for Patients With Advanced Melanoma Treated Beyond Progression: Analysis of 2 Phase 3 Clinical Trials. JAMA Oncology, 3 11: 1511-1519. doi:10.1001/jamaoncol.2017.1588

Author Long, Georgina V.
Weber, Jeffrey S.
Larkin, James
Atkinson, Victoria
Grob, Jean-Jacques
Schadendorf, Dirk
Dummer, Reinhard
Robert, Caroline
Márquez-Rodas, Ivan
McNeil, Catriona
Schmidt, Henrik
Briscoe, Karen
Baurain, Jean-François
Hodi, F Stephen
Wolchok, Jedd D.
Title Nivolumab for Patients With Advanced Melanoma Treated Beyond Progression: Analysis of 2 Phase 3 Clinical Trials
Journal name JAMA Oncology   Check publisher's open access policy
ISSN 2374-2445
Publication date 2017-11-01
Year available 2017
Sub-type Article (original research)
DOI 10.1001/jamaoncol.2017.1588
Open Access Status Not yet assessed
Volume 3
Issue 11
Start page 1511
End page 1519
Total pages 9
Place of publication Chicago, IL United States
Publisher American Medical Association
Language eng
Subject 2730 Oncology
1306 Cancer Research
Abstract Immune checkpoint inhibitors have demonstrated atypical response patterns, which may not be fully captured by conventional response criteria. There is a need to better understand the potential benefit of continued immune checkpoint inhibition beyond progression.

To evaluate the safety and potential benefit of nivolumab (anti-programmed cell death receptor 1) monotherapy beyond Response Evaluation Criteria in Solid Tumors (RECIST) v1.1-defined progression.

Pooled, retrospective analysis of data from phase 3 trials of nivolumab in treatment-naive patients with advanced melanoma (CheckMate 066 or CheckMate 067) conducted at academic and clinical cancer centers. Participants were patients treated beyond first disease progression, defined as those who received their last dose of nivolumab more than 6 weeks after progression (TBP group); and patients not treated beyond progression, who discontinued nivolumab therapy before or at progression (non-TBP group). Data analyses were conducted from November 6, 2015, to January 11, 2017.

Nivolumab (3 mg/kg every 2 weeks) administered until progression or unacceptable toxic effects. Patients could be treated beyond progression if deriving apparent clinical benefit and tolerating study drug, at the investigator's discretion.

Tumor response and safety in TBP and non-TBP patients.

Among 526 randomized patients (39% [n = 203] female; median age, 62 years [range, 18-90 years]), 306 (58%) experienced disease progression, including 85 (28%) TBP patients and 221 (72%) non-TBP patients. Twenty-four (28%) of the TBP patients had a target lesion reduction of greater than 30% after progression compared with baseline (TBP>30% group). At the time of this analysis, 65 (76%) TBP patients and 21 (87%) TBP>30% patients were still alive; 27 (32%) and 11 (46%), respectively, continued to receive treatment. Median (range) time from progression to last dose of treatment was 4.7 (1.4-25.8) months for TBP patients and 7.6 (2.4-19.4) months for TBP>30% patients. Median (range) time from progression to greater than 30% tumor reduction was 1.4 (0.2-7.0) months. Treatment-related select grade 3 to 4 adverse events were similar in the TBP and non-TBP groups (5 [6%] and 9 [4%], respectively).

A substantial proportion of selected patients treated with frontline nivolumab who were clinically stable and judged to be eligible for treatment beyond RECIST v1.1-defined progression by the treating investigators derived apparent clinical benefit without compromising safety. Further analysis will help define the potential benefit of continued nivolumab treatment beyond progression. Identifiers: NCT01721772 (CheckMate 066) and NCT01844505 (CheckMate 067).
Keyword Immune-Related Response
Solid Tumors
Untreated Melanoma
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: HERDC Pre-Audit
School of Public Health Publications
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Citation counts: TR Web of Science Citation Count  Cited 3 times in Thomson Reuters Web of Science Article | Citations
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Created: Wed, 15 Nov 2017, 12:34:11 EST