Real-world outcomes of patients with resected stage III melanoma treated with adjuvant therapies

Cancer Med. 2024 Jun;13(12):e7257. doi: 10.1002/cam4.7257.

Abstract

Background: Both immunotherapy (IO) and targeted therapy (TT) are used as adjuvant (adj) treatment for stage III melanoma, however, data describing real-world outcomes are limited. In addition, a significant proportion of patients relapse, for whom best management is unclear. The aim of our study was to assess the efficacy, and safety of adj anti-PD1 IO and TT in a real-world cohort of patients with resected stage III melanoma, and further delineate patterns of recurrence and treatment strategies.

Methods: We retrospectively analyzed 130 patients who received adj therapy (100 anti-PD1 IO and 30 TT).

Results: At a median follow-up of 30 months, median relapse-free survival (RFS) was 24.6 (95% CI, 17-not reached [NR]) versus 64 (95% CI, 29.5-NR) months for the TT and IO groups, respectively (p = 0.26). Median overall survival (OS) was NR for either subgroup. At data cutoff, 77% and 82% of patients in TT and IO arms were alive. A higher number of grade ≥3 treatment-related adverse events (AEs) were noted in the IO group (11% vs. 3%), however, a higher proportion of patients permanently discontinued adj therapy in the TT group (43% vs. 11%) due to toxicity. Strategies at relapse and outcomes were variable based on location and timing of recurrence. A significant number of patients who relapsed after adj IO received a second round of IO. Among them, patients who were off adj IO at relapse had superior second median RFS (mRFS2), compared to those who relapsed while on adj IO; mRFS2 was NR versus 5.1 months (95% CI, 2.5-NR), respectively, p = 0.02.

Conclusion: In summary, both TT and IO yielded prolonged RFS in a real-world setting, however, longer follow-up is needed to determine any potential OS benefit. Adj therapy, particularly TT, may not be as well tolerated as suggested in clinical trials, with lower completion rates (59% vs. 74%) in a real-life setting. Overall, patients who relapse during adj therapy have poor outcomes, while patients who relapse after discontinuation of adj IO therapy appear to benefit from IO re-treatment.

Keywords: adjuvant therapy; adverse events; immunotherapy; stage III melanoma; targeted therapy.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Chemotherapy, Adjuvant / methods
  • Female
  • Humans
  • Immune Checkpoint Inhibitors / adverse effects
  • Immune Checkpoint Inhibitors / therapeutic use
  • Immunotherapy / methods
  • Male
  • Melanoma* / drug therapy
  • Melanoma* / mortality
  • Melanoma* / pathology
  • Melanoma* / therapy
  • Middle Aged
  • Molecular Targeted Therapy
  • Neoplasm Recurrence, Local
  • Neoplasm Staging*
  • Retrospective Studies
  • Skin Neoplasms / drug therapy
  • Skin Neoplasms / mortality
  • Skin Neoplasms / pathology
  • Skin Neoplasms / therapy
  • Treatment Outcome

Substances

  • Immune Checkpoint Inhibitors