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
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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