Michele:

Although the combined immunotherapy via ipilimumab (Yervoy) + Nivolumab (Opdivo) that you mention is a standard-of-care therapy in NCCN and comparable EU-based guidelines, the selection of such anti–PD-1 monotherapy or nivolumab/ipilimumab combination therapy has to be carefully balanced because the data shows that although the combination provides a modest improvement in PFS over targeted therapies, it is unambiguously associated with a far higher risk of serious immune-mediated toxicities, with almost 50% of patients needing discontinuation of the regimen.

This suggests an alternative. The monoclonal anti-PD-1 antibody Pembrolizumab (Keytruda) has demonstrated improved response rates and PFS compared with chemotherapy or ipilimumab monotherapy, but more importantly, in clinical trials (KEYNOTE-006) it has been associated with a lower risk of AEs in patients with unresectable stage III or IV metastatic disease, as well as improved OS compared with ipilimumab, specifically, the relative risk of progression or death was decreased by 42% on a pembrolizumab (Keytruda) regimen, and the relative risk of death was decreased by 31 - 37%.

We have further data supporting this alternative from ASCO 2018 where it was reported that in the Keynote-001 Trial, for patients with advanced melanoma treated with pembrolizumab, 34% of those patients are still alive five years after treatment and that 73% of all responding patients are still maintaining their response. This represents a distinct advantage of long-term durable response and survival outcomes compared to other conventional melanoma treatments, and the results of several in-progress clinical trial should shortly further clarify the optimal deployment of pembrolizumab monotherapy or partnered combination regimens, and what the most effective partner agent may be.

Constantine Kaniklidis

Director, Medical Research, No Surrender Breast Cancer Foundation (NSBCF)

Oncology Reviewer, Current Oncology

Member, European Association for Cancer Research (EACR)

Society for Integrative Oncology (SIO)

International Cardioncology Society, North America (ICOSNA)

Hi Michele,

You’ve got another form of immunotherapy, which is a single agent rather than a combined therapy. An anti PD-1 (Pembrolizumab) is a therapy for metastatic melanoma, that’s used as a single agent.

By the way, ordinary cytotoxic chemotherapy gas no role.

Thank you for your answers. Do you have any papers to suggest showing effects of monoclonal anti-PD-1 antibody Pembrolizumab (Keytruda)?

Thanks again

Michele

Hi Michele,

There are few clinical trials lead to FDA aproval in advanced melanoma in different circumstances. Such as

KEYNOTE-006

KEYNOTE-002

KEYNOTE-001

Michele:

Pembrolizumab (Keytruda) in Melanoma:

Ascierto PA DR, et al. KEYNOTE-002 Part 3: Phase 2 randomized study of 1L dabrafenib (D) and trametinib (T) plus pembrolizumab (Pembro) or placebo (PBO) for BRAF-mutant advanced melanoma. ESMO 2018 Congress.

Carlino MS, Long GV, Schadendorf D, et al. Outcomes by line of therapy and programmed death ligand 1 expression in patients with advanced melanoma treated with pembrolizumab or ipilimumab in KEYNOTE-006: A randomised clinical trial. Eur J Cancer. 2018 09; 101:236-243.

Daud AI, Wolchok JD, Robert C, et al. Programmed Death-Ligand 1 Expression and Response to the Anti-Programmed Death 1 Antibody Pembrolizumab in Melanoma. J Clin Oncol. 2016 12; 34(34):4102-4109.

Eggermont AMM, Blank CU, Mandala M, Long GV, Atkinson V, Dalle S, et al. Adjuvant Pembrolizumab versus Placebo in Resected Stage III Melanoma. The New England journal of medicine 2018;378:1789-801.

Hamid O, Robert C, Daud A, Hodi FS, Hwu W-J, Kefford R, et al. 5-year survival outcomes in patients (pts) with advanced melanoma treated with pembrolizumab (pembro) in KEYNOTE 001. Journal of Clinical Oncology 2018;36:9516-

Hodi FS, Hwu WJ, Kefford R, et al. Evaluation of Immune-Related Response Criteria and RECIST v1.1 in Patients With Advanced Melanoma Treated With Pembrolizumab. J Clin Oncol. 2016 05 01; 34(13):1510-7.

Kluger HM, Chiang V, Mahajan A, Zito CR, Sznol M, Tran T, et al. Long-Term Survival of Patients With Melanoma With Active Brain Metastases Treated With Pembrolizumab on a Phase II Trial. Journal of clinical oncology 2018:JCO1800204.

Long GV, Schachter J, Ribas A, Arance AM, Grob J-J, Mortier L, et al. 4-year survival and outcomes after cessation of pembrolizumab (pembro) after 2-years in patients (pts) with ipilimumab (ipi)-naive advanced melanoma in KEYNOTE-006. Journal of Clinical Oncology 2018;36:9503-

Robert C, Ribas A, Hamid O, et al. Three-year overall survival for patients with advanced melanoma treated with pembrolizumab in KEYNOTE-001. Journal of Clinical Oncology 2016 34:15_suppl, 9503-9503.

Robert C, Ribas A, Hamid O, Daud A, Wolchok JD, Joshua AM, et al. Durable Complete Response After Discontinuation of Pembrolizumab in Patients With Metastatic Melanoma. Journal of clinical oncology : official journal of the American Society of Clinical Oncology 2018;36:1668-74.

Schachter J, Ribas A, Long GV, Arance A, Grob JJ, Mortier L, et al. Pembrolizumab versus ipilimumab for advanced melanoma: final overall survival results of a multicentre, randomised, open-label phase 3 study (KEYNOTE-006). Lancet 2017;390:1853-62.