Melanoma: New Drugs and New Challenges (Part 2 of 2)


Editor’s note: This is part 2 of a 2-part post on the latest research in melanoma. To learn about research into drug combinations for melanoma that may work better than single drugs, check out Melanoma: New Drugs and New Challenges (Part 1 of 2).

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…


OPTiM Follow-up Shows Improved CR Rate With T-VEC in Melanoma

“A retrospective analysis of the phase III OPTiM study found that treatment with talimogene laherparepvec (T-VEC; Imlygic) resulted in complete responses (CR) in 17% of patients seen in all stages of melanoma. Median time to achieve a CR was 8.6 (6.0–13.6) months. A high proportion of response occurred in patients with early-stage disease and lower tumor burden, according to study authors.

“In OPTiM, a phase III trial in 436 patients with unresected stage IIIB to IV melanoma, T-VEC improved durable response rates from 2.1% to 16.3% versus subcutaneous GM-CSF. Overall response rates (ORR) for T-VEC and GM-CSF were 26.4% and 5.7%, respectively. Median overall survival (OS) was 23.3 months with T-VEC and 18.9 months with GM-CSF (HR, 0.79; 95% CI, 0.62–1.00; P = .051).”


T-VEC Extends OS in Patients with Unresected Stage III/IV Melanoma

“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.”


Advanced Melanoma: The Promise and Shortcomings of Drugs Injected Directly into Tumors


In the past 3 years, the treatment landscape for metastatic melanoma has changed dramatically. We saw the advent of drugs that inhibit mutant BRAF and activate MEK proteins (vemurafenib, dabrafenib, and trametinib) and drugs known as immune checkpoint inhibitors (ipilimumab, Keytruda, Opdivo, and others). These treatments are ‘systemic’; that is, they are taken by mouth or injected directly into the bloodstream and spread throughout the body. However, as I reported earlier this year, drugs that are injected directly into tumors—’intralesional drugs’—have recently gained some attention. Two of them were featured at the 2014 American Society of Clinical Oncology (ASCO) Annual Meeting. New data, and doubts, on these drugs have since emerged. Continue reading…


Adding Sargramostim to Ipilimumab Prolonged Survival in Metastatic Melanoma Trial

The gist: People with metastatic melanoma who are being treated with the drug ipilimumab (Yervoy) may live several months longer if they also take another drug called granulocyte-macrophage colony-stimulating factor (GM-CSF). In a recent clinical trial, researchers compared patients who took just ipilimumab with patients who took both ipilimumab and GM-CSF. Patients who took both lived several months longer. However, GM-CSF didn’t increase the amount of time that passed before cancer returned.

“The addition of sargramostim, a systemic granulocyte-macrophage colony-stimulating factor (GM-CSF), to the anti-CTLA-4 ipilimumab resulted in a significant improvement in overall survival in patients with metastatic melanoma when compared with treatment with ipilimumab alone, according to phase II study results published recently in JAMA: Dermatology. However, no difference in progression-free survival was found between the two study groups.

“ ‘The lack of correlation between overall survival and progression-free survival in this study presents challenges to clinical management and drug development because conventional radiographic criteria have not proven reliable for determining patient benefit,’ wrote researchers led by F. Stephen Hodi, MD, of the Dana-Farber Cancer Institute. ‘This introduces important considerations for the evaluation of treatment efficacy with particular immune therapies such as ipilimumab.’

“Previous research has shown therapeutic synergy between CTLA-4 blockade and GM-CSF secreting tumor cell vaccines. In addition, the combination of systemic GM-CSF with CTLA-4 blockade in patients with hormone-refractory prostate cancer resulted in clinical responses in more than half of patients with PSA declines.”


Amgen Presents New Data On Talimogene Laherparepvec As Single Agent And Combination Therapy In Metastatic Melanoma At ASCO

“Amgen today announced new data from two key clinical trials that support the potential of talimogene laherparepvec, a novel, investigational oncolytic immunotherapy, as both a single agent and as part of a combination regimen in patients with metastatic melanoma. The findings were presented at the 50th Annual Meeting of the American Society of Clinical Oncology (ASCO) in Chicago.”

Editor’s note: This article describes promising results for a melanoma treatment called talimogene laherparepvec (T-VEC), an immunotherapy that boosts a patient’s own immune system to fight cancer. Previous testing of the drug has found mixed results.


Immunotherapy Duo Improves Survival in Metastatic Pancreatic Cancer

Overall survival was improved in metastatic pancreatic cancer patients through an innovative immunotherapy strategy in a multicenter study reported at the 2014 Gastrointestinal Cancers Symposium.

“ ‘This is the first time a randomized study has shown that immunotherapy is effective in pancreatic cancer,’ said Dung T. Le, MD, Assistant Professor of Medicine at the Johns Hopkins University Sidney Kimmel Comprehensive Cancer Center, Baltimore. ‘This is just a first step, and we believe we’ll be able to take this approach further.’ ”

“The novel treatment, which may be better tolerated than standard chemotherapy, involves two different anticancer vaccines: GVAX Pancreas followed by CRS-207. GVAX is composed of pancreatic cancer cells that have been genetically modified to secrete granulocyte-macrophage colony-stimulating factor (GM-CSF), which stimulates the immune system. GVAX is given with low-dose cyclophosphamide to inhibit regulatory T cells and boost the vaccine’s efficacy. The second vaccine, CRS-207, is live-attenuated Listeria monocytogenes (Lm), which has been genetically modified to be safe for human use while retaining its ability to stimulate an immune response against the protein mesothelin on pancreatic tumor cells.

“The combination essentially trains the body to recognize and attack pancreatic tumors. In mouse tumor models, Lm/GVAX vaccines are synergistic, and in a phase I study of CRS-207, patients with pancreatic ductal adenocarcinoma who had received prior GVAX lived more than 15 months, Dr. Le explained.”

Editor’s note: Immunotherapy treatments work by boosting a patient’s own immune system to fight cancer. This story describes such a treatment, which combines two “cancer vaccines” called GVAX Pancreas and CRS-207. Scientists found promising results for the treatment in pancreatic cancer patients.


T-VEC Keeps Shrinking Melanomas

An experimental vaccine that is injected into melanomas can shrink them for an average of 8 months, according to findings presented at the American Society of Clinical Oncology’s 2013 meeting. Called talimogene laherparepvec (T-VEC), this immunotherapy consists of a virus engineered to carry human genes for granulocyte macrophage colony-stimulating growth factor (GM-CSF). Once inside a tumor, T-VEC kills tumor cells both by bursting them and by boosting the immune response against them. In a phase III clinical trial, melanomas shrank in 16% of those injected with T-VEC (48 out of 295) compared to just 2% of those treated directly with GM-CSF (30 out of 141). Moreover, melanomas disappeared completely in more than 10% of those treated with T-VEC. Doctors caution that because T-VEC is injected into melanomas, this treatment is only practical for people with accessible tumors.


Anti-Melanoma Vaccine May Extend Life

Results of a late-stage clinical trial suggest that an experimental immunotherapy may boost survival in people with melanoma. Called talimogene laherparepvec (T-VEC), the vaccine includes a gene called granulocyte-macrophage colony-stimulating factor (GM-CSF) that stimulates the immune system. The researchers found that people injected with T-VEC lived an average of 4 months longer than those treated with GM-CSF on its own (23 vs 19 mo). In addition, T-VEC made more tumors disappear or shrink by at least half.