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Clinical Trial
. 2024 Nov;42(31):3702-3712.
doi: 10.1200/JCO.23.01448. Epub 2024 Aug 5.

Outcomes With Postrecurrence Systemic Therapy Following Adjuvant Checkpoint Inhibitor Treatment for Resected Melanoma in CheckMate 238

Jeffrey Weber  1 , Michele Del Vecchio  2 , Mario Mandalá  3 , Helen Gogas  4 , Ana M Arance  5 , Stephane Dalle  6 , C Lance Cowey  7 , Michael Schenker  8 , Jean-Jacques Grob  9 , Vanna Chiarion-Sileni  10 , Iván Márquez-Rodas  11 , Marcus O Butler  12 , Anna Maria Di Giacomo  13 , Luis de la Cruz-Merino  14 , Petr Arenberger  15 , Victoria Atkinson  16 , Andrew Hill  17 , Leslie A Fecher  18 , Michael Millward  19 , Nikhil I Khushalani  20 , Paola Queirolo  21 , Georgina V Long  22 , Maurice Lobo  23 , Margarita Askelson  23 , Paolo A Ascierto  24 , James Larkin  25
Affiliations
Clinical Trial

Outcomes With Postrecurrence Systemic Therapy Following Adjuvant Checkpoint Inhibitor Treatment for Resected Melanoma in CheckMate 238

Jeffrey Weber et al. J Clin Oncol. 2024 Nov.

Abstract

Purpose: In phase III CheckMate 238, adjuvant nivolumab significantly improved recurrence-free survival compared with ipilimumab in patients with resected stage IIIB-C/IV melanoma without a significant difference in overall survival (OS). Here, we investigate progression-free survival (PFS) and OS after postrecurrence systemic therapy.

Patients and methods: Patients 15 years or older with resected stage IIIB-C/IV melanoma were stratified by stage and tumor PD-L1 status and randomly assigned to receive nivolumab 3 mg/kg every 2 weeks, or ipilimumab 10 mg/kg every 3 weeks for four doses and then every 12 weeks for 1 year or until disease recurrence, unacceptable toxicity, or withdrawal of consent. Patients with recurrence in each group were assessed for PFS and OS from subsequent systemic therapy (SST) initiation per recurrence timing (≤12 months [early] v >12 months [late] from initial therapy).

Results: Recurrences occurred in 198 (44%) of 453 nivolumab-treated patients (122 early, 76 late) and 232 (51%) of 453 ipilimumab-treated patients (160 early, 72 late). Median PFS on next-line systemic therapy for nivolumab-treated patients recurring early versus late was 4.7 versus 12.4 months (24-month rates, 16% v 31%); median OS was 19.8 versus 42.8 months (24-month rates: 37% v 73%). In response to subsequent therapy, patients on nivolumab with late versus early recurrence were more likely to benefit from anti-PD-1 monotherapy. Nivolumab-treated patients with either an early or late recurrence benefitted from an ipilimumab-based therapy or targeted therapy, each with similar OS.

Conclusion: Postrecurrence survival was longer for patients who recurred >12 months. Patients on nivolumab who recurred early benefitted from SST but had better survival with ipilimumab-based regimens or targeted therapy compared with anti-PD-1 monotherapy.

Trial registration: ClinicalTrials.gov NCT02388906.

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Conflict of interest statement

The following represents disclosure information provided by authors of this manuscript. All relationships are considered compensated unless otherwise noted. Relationships are self-held unless noted. I = Immediate Family Member, Inst = My Institution. Relationships may not relate to the subject matter of this manuscript. For more information about ASCO's conflict of interest policy, please refer to www.asco.org/rwc or ascopubs.org/jco/authors/author-center.

Open Payments is a public database containing information reported by companies about payments made to US-licensed physicians (Open Payments).

Figures

FIG 1.
FIG 1.
Kaplan-Meier curve of PFS from time of subsequent systemic therapy for patients who received nivolumab on study and had a recurrence at any time and by recurrence at ≤12 or >12 months from treatment initiation (A) and for patients who received ipilimumab on study and had a recurrence at any time and by recurrence at ≤12 or >12 months from treatment initiation (B). PFS, progression-free survival.
FIG 2.
FIG 2.
Twelve-month (A) and 24-month (B) PFS rates from time of subsequent therapy for patients who received nivolumab on study and had a recurrence ≤12 or >12 months from treatment initiation and 12-month (C) and 24-month (D) PFS rates from time of subsequent therapy for patients who received ipilimumab on study and had a recurrence ≤12 or >12 months from treatment initiation. PFS, progression-free survival.
FIG 3.
FIG 3.
Kaplan-Meier curve of OS from time of subsequent systemic therapy for patients who received nivolumab on study and had a recurrence at any time and by recurrence at ≤12 or >12 months from treatment initiation (A) and for patients who received ipilimumab on study and had a recurrence at any time and by recurrence at ≤12 or >12 months from treatment initiation (B). NR, not reached; OS, overall survival.
FIG 4.
FIG 4.
Twelve-month (A) and 24-month (B) OS rates from time of subsequent therapy for patients who received nivolumab on study and had a recurrence ≤12 or >12 months from treatment initiation and 12-month (C) and 24-month (D) OS rates from time of subsequent therapy for patients who received ipilimumab on study and had a recurrence ≤12 or >12 months from treatment initiation. OS, overall survival.
FIG 5.
FIG 5.
(A) Nature of first unresectable recurrence in patients who received nivolumab, (B) nature of recurrence in patients who received ipilimumab, (C) sites of metastasis at first distant recurrence in patients who received nivolumab, and (D) sites of metastasis at first distant recurrence in patients who received ipilimumab, by time after random assignment (≤12 months or >12 months). aPatients could have been counted in more than one site recorded. bOther, including intramuscular, limb, neck, and trunk.
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Comment in

References

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