Villejuif, 31 may 2017
Metastatic melanoma: PD1-blocking immunotherapy confirms its long-term clinical efficacy, even after cessation of treatment
Pembrolizumab, an immunotherapeutic agent that blocks the PD1 (Programmed-cell death 1) receptor, prolongs the life of patients and the benefits of treatment persist in the long-term, even after cessation of treatment. On 4th June, Professor Caroline Robert, Head of the Gustave Roussy Dermatology Department, will present all the results of this study in an oral session devoted to melanoma and other skin cancers at the Congress of the American Society of Clinical Oncology (Asco), in Chicago, the largest world congress in oncology.
In 2011, ipilimumab (ipi), the first immunotherapeutic drug for the treatment of metastatic melanoma, had already been shown to markedly improve the prognosis in patients with this skin cancer, for which no effective treatment had previously been available. Since then, a new generation of anti-PD1 antibody immunotherapeutic agents has been developed, in particular pembrolizumab (pembro), which was marketed in September 2015. Gustave Roussy, by virtue specifically of the work of Caroline Robert, has made a major contribution to the validation of these drugs. In the phase 3 international clinical study launched in 2013 by the MSD Company, Keynote-006, pembrolizumab was compared to ipi. Ipi is administered as four injections at three week intervals, whereas pembro is a long-term treatment for which the optimal duration of therapy with injections given every three weeks is not known. In this clinical trial, the treatment was stopped after two years in those patients who were still on pembrolizumab. The trial (834 patients) had already shown that pembro was superior to ipi: it increased patient survival as well as the period during which the disease did not progress. It also displayed less toxicity than ipi.
We now have findings in the even longer term, having observed those patients who stopped pembrolizumab after two years of treatment. “We have a median follow-up period of almost three years (33 months) in several hundred patients. Half of those who had pembro are still alive, compared with only 39% of those treated with ipi alone. 31% of the former group have not experienced disease progression, compared with 14% of the latter. In 41% of the patients treated with pembro, the malignant foci regressed completely or partially, compared with 16% on ipi. Of those who received the two full years of pembro treatment, 98% are still alive nine months later and 91% did not have disease progression,” explained Caroline Robert.
Melanoma constitutes between 2 and 3 % of all cancers, and 10 % of skin cancers, but its incidence has doubled every 10 years over recent decades. Thus, 11,000 patients were affected by it in France in 2012. The responsibility for this is excessive exposure to the sun of the palest skins, especially in childhood. In addition, melanoma is particularly dangerous because it can be fatal in around one case in ten, especially if it is diagnosed late at a stage when metastases are present. Up to the early 2010s, there was no effective treatment for advanced disease of this type.
Immunotherapy has intervened to change the situation. Today the anti-PD1 agents, of which pembro is one, play a major role in the strategy of helping the patient’s defence mechanisms to fight cancer.
"While it remains difficult to talk of cure, we can still say that these results are very encouraging. Only 9% of patients had disease progression at nine months after cessation of treatment and we are now concentrating on those and on novel combined therapies to reduce the relapse rate further," concluded Caroline Robert.
Title : Long-term outcomes in patients (pts) with ipilimumab (ipi)-naive advanced melanoma in the phase 3 KEYNOTE-006 study who completed pembrolizumab (pembro) treatment.
Oral presentation by Caroline Robert, Gustave Roussy
Session: Melanoma/Skin Cancers
Sunday 4 june, 9 h 12 (local time)
Place: Arie Crown Theater
Abstract n° 9504 available sur http://abstracts.asco.org