eUpdate – Cutaneous Melanoma Treatment Recommendations

eUpdate – Cutaneous Melanoma Treatment Recommendations

Published: 19 September 2016. Authors: ESMO Guidelines Committee

Clinical Practice Guidelines

This update refers to the Cutaneous melanoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Dummer R, Hauschild A, Lindenblatt N, et al. Ann Oncol (2015) 26 (suppl 5): v126-v132.

Section

Treatment of systemic metastatic disease (stage IV)

Text update

In a double-blinded prospective randomised trial, nivolumab was compared with ipilimumab and the ipilimumab/nivolumab combination. Nivolumab monotherapy compared to ipilimumab was scored with an ESMO Magnitude of Clinical Benefit Scale (MCBS) score of 4, as it resulted in a statistically and clinically significant progression-free survival (PFS) benefit, without increased toxicity. The nivolumab+ipilimumab combination was scored with an ESMO-MCBS score of 2, the lower score reflecting the presence of only PFS data as well as the increased toxicity of the combination. Programmed death ligand 1 (PD-L1) expression may be a relevant marker in this context, however data are not available nor mature for the ESMO-MCBS scoring of the nivolumab+ipilimumab combination compared to ipilimumab in the PD-L1-negative melanoma subgroup of patients.

Recommendation

For patients with metastatic melanoma, treatment options for first-line setting include the anti-PD-1 antibody nivolumab which showed a clinically and statistically significant PFS benefit over ipilimumab, with a high MCBS score of 4 [II, B].

Magnitude of Clinical Benefit Scale (MCBS) table for new therapies/indications in Cutaneous Melanoma*

Therapy Disease setting Trial Control Absolute survival gain HR (95% CI) QoL/toxicity MCBS score**
Nivolumab, a PD-1 checkpoint inhibitor Unresectable stage III or IV melanoma, 1st line setting Combined Nivolumab and Ipilimumab or Monotherapy in Untreated Melanoma [1]
 
Phase III
 
NCT01844505
Ipilimumab, in previously untreated patients with unresectable stage III or IV melanoma.
 
Control PFS:
2.9 months
PFS gain:
4.0 months
PFS HR:
0.57
(0.43-0.76)
Improved toxicity profile 4 (Form 2b)
Nivolumab (a PD-1 checkpoint inhibitor) + ipilimumab (a CTLA-4 checkpoint inhibitor) Unresectable stage III or IV melanoma, 1st line setting Combined Nivolumab and Ipilimumab or Monotherapy in Untreated Melanoma [1]
 
Phase III
 
NCT01844505
Ipilimumab, in previously untreated patients with unresectable stage III or IV melanoma.
 
Control PFS:
2.9 months
PFS gain***:
8.6 months
PFS HR:
0.42 (0.31-0.57)
Deteriorated toxicity profile 2 (Form 2b)
Nivolumab (a PD-1 checkpoint inhibitor) + ipilimumab (a CTLA-4 checkpoint inhibitor) Unresectable stage III or IV melanoma, 1st line setting.
 
Pre-specified subgroup of PD-L1-negative melanoma
Combined Nivolumab and Ipilimumab or Monotherapy in Untreated Melanoma [1]
 
Phase III
 
NCT01844505
Ipilimumab, in previously untreated patients with unresectable stage III or IV melanoma.
 
Control PFS:
2.9 months
PFS gain:
8.3 months
PFS HR:
Not available
Not available Not available

*EMA approvals in 2016 to end August 2016.

**ESMO-MCBS version 1.0 [2]

***Gain > nivolumab alone was only observed with PD-L1 positive melanoma

CI, confidence interval; QoL, quality of life; PD-1, programmed death 1; PFS, progression-free survival; HR, hazard ratio; CTLA-4, cytotoxic T-lymphocyte-associated antigen 4; EMA, European Medicines Agency; PD-L1, programmed death-ligand 1

References

  1. Larkin J, Chiarion-Sileni V, Gonzalez R, et al. Combined nivolumab and ipilimumab or monotherapy in untreated melanoma. N Engl J Med 2015;373:23-34.
  2. Cherny NI, Sullivan R, Dafni U et al. A standardised, generic, validated approach to stratify the magnitude of clinical benefit that can be anticipated from anti-cancer therapies: the European Society for Medical Oncology Magnitude of Clinical Benefit Scale (ESMO-MCBS). Ann Oncol 2015; 26: 1547–1573.