As always, the more new treatments become available in melanoma, the more new challenges arise. With eight new drugs approved for melanoma in the last five years, oncologists may sometimes face the difficult choice of what drugs to choose for a patient’s first-line treatment. Immune checkpoint drugs sometimes cause serious side effects, but progress is being made on how to treat these and also how to treat patients with pre-existing autoimmune conditions. New approaches are needed in efforts to prevent recurrence of melanomas diagnosed at earlier stages of disease progression. These and other challenges are discussed below. Continue reading…
“Amgen AMGN, +1.94% today announced that the Committee for Medicinal Products for Human Use (CHMP), the scientific committee of the European Medicines Agency (EMA), has adopted a positive opinion recommending that IMLYGIC™ (talimogene laherparepvec) be granted approval for the treatment of adults with unresectable melanoma that is regionally or distantly metastatic (Stage IIIB, IIIC and IVM1a) with no bone, brain, lung or other visceral disease. If approved by the European Commission, IMLYGIC would be the first in a class of novel agents known as oncolytic immunotherapies.
“IMLYGIC, administered via intralesional injection, is designed to cause the death of tumor cells and to initiate an anti-tumor immune response.”
“Patients with unresected stage IIIb, stage IIIc or stage IV melanoma treated with talimogene laherparepvec demonstrated a durable OS advantage compared with those who received granulocyte-macrophage colony–stimulating factor, according to study results presented at the HemOnc Today Melanoma and Cutaneous Malignancies meeting.
“Talimogene laherparepvec (T-VEC, Amgen) is a systemically active oncolytic immunotherapy derived from herpes simplex virus type-1. Upon injection directly into tumor tissue, T-VEC selectively infects and replicates in tumor cells. The virus replication leads to tumor cell lysis and exposure of tumor-specific antigens to the immune system, resulting in a local and systemic immune activation and an immune-mediated destruction of tumor cells throughout the body.
“T-VEC also is engineered to produce GM-CSF to enhance the local and systemic antitumor immune response, according to study background.”
“Recruitment will begin soon for a phase 3 trial that will compare intralesional PV-10 with chemotherapy in patients with stage IIIb or IIIc melanoma, according to a presenter at the HemOnc Today Melanoma and Cutaneous Malignancies meeting.
“The analysis will include 225 patients. Two-thirds will be randomly assigned to monthly injections with PV-10 (Provectus), a sterile, non-pyrogenic solution of rose bengal disodium that destroys tumors by necrosis. The other patients will be assigned standard-dose chemotherapy with dacarbazine or temozolomide.
“All patients must have cutaneous and subcutaneous disease with no active nodal disease, and all lesions must be BRAF wild type. All patients must be either refractory to or not candidates for systemic immunotherapy.
“ ‘This is a trial design that is difficult to do,’ Sanjiv S. Agarwala, MD, chief of oncology and hematology at St. Luke’s Cancer Center, professor at Temple University School of Medicine and a HemOnc Today Editorial Board member, said during a presentation. ‘We’re going to need a lot of centers, and there will be smaller groups per center because these are not easy patients to find. But we’re not going to deprive patients of the ability to get checkpoint inhibitors if that is the right treatment for them.’ ”
The gist: Researchers tested a new melanoma treatment in a clinical trial—a research study with volunteer patients. The treatment combines the targeted drugs dabrafenib and trametinib. All of the patients who participated in the trial had inoperable stage IIIC or stage IV melanoma. Also, each patient’s tumors had one of two particular mutations in the BRAF gene, known as V600E and V600K. In the trial, patients who were treated with the combination therapy had significantly lower chances of their cancer worsening and lower chances of death.
“A world-first study in today’s New England Journal of Medicine heralds the efficacy of a targeted combination drug therapy after reporting major declines in the risk of disease progression and death in people with metastatic melanoma.
“The multi-centre, double-blind, randomised, phase 3 trial compared oral dabrafenib (150 mg twice daily) and oral trametinib (2 mg once daily) combination therapy with oral dabrafenib (150 mg twice daily) and placebo.
“All trial patients had inoperable stage 3C or 4 metastatic melanoma that had a BRAF gene mutation V600E or V600K. Among cancer patients with metastatic melanoma, about 40 per cent have a BRAF gene mutation – an abnormality that assists some melanoma tumours to grow and spread.
“Led by Associate Professor Georgina Long of Melanoma Institute Australia at the University of Sydney, the finding affirms accumulating evidence of the efficacy of targeted combination therapies in extending life and halting disease progression in patients with cancers that carry genetic mutations that resist monotherapies.”
Editor’s note: Before a drug can be made widely available to patients in the European Union, it must first be approved by the European Medicines Agency. The drug company Amgen recently submitted a proposal for approval of its melanoma treatment talimogene laherparepvec (T-VEC). T-VEC is a modified virus that is injected directly into tumors, where it destroys tumor cells. It has shown some promising results in clinical trials—research studies in volunteer patients.
“Amgen announced the submission of a marketing authorization application to the European Medicines Agency for talimogene laherparepvec for the treatment of regionally or distantly metastatic melanoma in adults.
“If the application is approved, talimogene laherparepvec will represent the first in a class of novel agents known as oncolytic immunotherapies, according to a company press release.
“The marketing authorization application contains data from more than 400 patients and is based on a global, randomized, open-label, phase 3 trial evaluating its efficacy and safety in patients with stage IIIB, IIIC or IV melanoma when resection was not recommended.”