ASCO 2017 - Metastatic melanoma: PD1-blocking immunotherapy confirms its long-term clinical efficacy, even after cessation of treatment

Villejuif,  31 may 2017

ASCO 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

► Long-term efficacy of pembrolizumab in advanced melanoma: see the video on Youtube