Analysis of patients (pts) with in-transit metastases treated with nivolumab (NIVO) or ipilimumab (IPI) in CheckMate 238.

Authors

null

James Larkin

The Royal Marsden Hospital NHS Foundation Trust, London, United Kingdom

James Larkin , Helen Gogas , Michele Del Vecchio , Michele Maio , Petr Arenberger , Ana Maria Arance , Jean-Jacques Grob , Vanna Chiarion-Sileni , Karl D. Lewis , Laurent Mortier , Patrick Alexander Ott , Georgina V. Long , Alfonsus Van Den Eertwegh , C. Lance Cowey , Michael Schenker , Marcus O. Butler , Maurice Lobo , Margarita Askelson , Paolo Antonio Ascierto , Jeffrey S. Weber

Organizations

The Royal Marsden Hospital NHS Foundation Trust, London, United Kingdom, National and Kapodistrian University of Athens, Athens, Greece, Head, Unit of Melanoma Medical Oncology Department of Medical Oncology and Hematology, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Milan, Italy, Center for Immuno-Oncology, University Hospital of Siena, Siena, Italy, Department of Dermatology, Charles University Third Faculty of Medicine and University Hospital Kralovske Vinohrady, Prague, Czech Republic, Department of Medical Oncology, Hospital Clinic Barcelona, Barcelona, Spain, Aix-Marseille University, CHU Timone, Marseille, France, Head of Melanoma Cancer Unit, Melanoma Oncology Unit, Veneto Institute of Oncology IOV–IRCCS, Padua, Italy, University of Colorado Comprehensive Cancer Center, Aurora, CO, Universite Lille, Centre Hospitalier Regional Universitaire de Lille, Lille, France, Dana-Farber Cancer Institute, Boston, MA, Professor of Melanoma Medical Oncology and Translational Research, Melanoma Institute Australia, University of Sydney, and Royal North Shore and Mater Hospitals, North Sydney, Australia, Amsterdam University Medical Center, VUMC, Amsterdam, Netherlands, Medical Oncology, Texas Oncology-Baylor Charles A. Sammons Cancer Center, Dallas, TX, Oncology Center, Oncology Center Sf Nectarie Ltd., Craiova, Romania, Tumor Immunotherapy Program, Princess Margaret Cancer Centre, University Health Network, University of Toronto, Toronto, ON, Canada, Bristol Myers Squibb, Princeton, NJ, Biostatistics, Bristol Myers Squibb, Princeton, NJ, Istituto Nazionale Tumori IRCCS Fondazione Pascale, Naples, Italy, Laura and Isaac Perlmutter Cancer Center, NYU Langone Health, New York, NY

Research Funding

Pharmaceutical/Biotech Company
Bristol Myers Squibb, Pharmaceutical/Biotech Company

Background: In the phase 3 CheckMate 238 study, NIVO has demonstrated improved recurrence-free survival (RFS) and distant metastasis-free survival (DMFS) vs IPI in pts with resected stage IIIB–C or IV melanoma, which was sustained at the 4-y analysis. Having in-transit metastases/satellites (ITM) is a poor prognostic factor, and pts with ITM are generally omitted from clinical trials. This study was the first and only adjuvant checkpoint inhibitor trial to include pts with ITM. Here, we present post hoc outcomes in this subgroup. Methods: Pts aged ≥15 y with completely resected stage IIIB–C or IV melanoma stratified by stage and tumor PD-L1 status were randomized 1:1 to NIVO (3 mg/kg Q2W; n = 453) or IPI (10 mg/kg Q3W for 4 doses, Q12W thereafter; n = 453) for a maximum of 1 y or until disease recurrence/unacceptable toxicity. Pts with ITM, with or without synchronous nodal involvement, were included. The primary study endpoint was RFS; overall survival (OS) was a secondary endpoint; and DMFS was exploratory. Results: Each of the 2 treatment groups had 164 pts with ITM. Baseline characteristics were generally similar between treatment groups in pts with or without ITM; in pts with ITM vs without ITM, tumor ulceration was less frequent in NIVO-treated pts, and fewer IPI-treated pts had PD-L1 expression ≥5%. RFS and DMFS favored NIVO vs IPI in all ITM subgroups (table). OS was similar to the intention-to-treat (ITT) population with no differences noted between treatment groups or between ITM subgroups. Among pts with or without ITM, dominant metastatic sites were lung and lymph nodes, followed by brain, liver, and soft tissue (in varying order). Similar metastasis patterns were observed in pts with ITM regardless of nodal involvement. Treatment-related adverse events (any grade and grade 3/4) in pts with ITM were similar to those of the ITT population. Conclusions: Results of this post hoc 4-y analysis of CheckMate 238 showed that safety and efficacy were similar in pts with or without ITM, supporting the use of adjuvant NIVO in pts with ITM, regardless of nodal involvement. Clinical trial information: NCT02388906




No ITM


No ITM


ITM


ITM
ITM with nodes
ITM with nodes
ITM, no nodes
ITM, no nodes
Treatment
NIVO

(n = 206)
IPI

(n = 202)
NIVO

(n = 164)
IPI

(n = 164)
NIVO

(n = 83)
IPI

(n = 90)
NIVO

(n = 81)
IPI

(n = 74)
4-y RFS, % (95% CI)
54

(47–61)
46

(38–52)
50

(42–58)
38

(30–45)
53

(41–63)
35

(24–45)
49

(37–59)
41

(29–52)
HR (95% CI)
0.77

(0.58–1.02)

0.63

(0.47–0.86)

0.57

(0.37–0.87)

0.72

(0.47–1.12)

4-y DMFS, % (95% CI)
60

(53–67)
53

(46–60)
58

(49–65)
53

(45–61)
59

(47–69)
51

(39–62)
56

(43–66)
56

(44–67)
HR (95% CI)
0.79

(0.58–1.07)

0.79

(0.56–1.11)

0.71

(0.44–1.14)

0.90

(0.55–1.49)

4-y OS, % (95% CI)
76

(69–81)
75

(68–81)
79

(72–85)
79

(72–85)
78

(67–86)

77

(67–85)
81

(70–88)
82

(70–89)
HR (95% CI)
0.93

(0.63–1.36)

0.89

(0.55–1.43)

0.81

(0.42–1.54)

1.03

(0.50–2.11)

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Abstract Details

Meeting

2021 ASCO Annual Meeting

Session Type

Poster Session

Session Title

Melanoma/Skin Cancers

Track

Melanoma/Skin Cancers

Sub Track

Local-Regional Disease

Clinical Trial Registration Number

NCT02388906

Citation

J Clin Oncol 39, 2021 (suppl 15; abstr 9569)

DOI

10.1200/JCO.2021.39.15_suppl.9569

Abstract #

9569

Poster Bd #

Online Only

Abstract Disclosures