Briefer Biochemotherapy Yields Better Relapse-Free Survival but Greater Toxicity vs 1-Year High-Dose Interferon in High-Risk Melanoma

The gist: Compared to a standard treatment, an alternative, shorter treatment for stage III melanoma may lengthen the amount of time patients go without their cancer returning. However, it has more toxic side effects. And compared to the standard, it doesn’t lengthen life. The alternative treatment uses the drugs cisplatin, vinblastine, dacarbazine, interleukin-2, and interferon alfa-2b. In a clinical trial with volunteer patients, it was compared to longer (1-year), high-dose treatment with the drug interferon alfa-2b. The trial involved people aged 10 years and older with stage IIIA-N2a through IIIC-N3 melanoma.

“In a phase III trial (Southwest Oncology Group Intergroup S0008) reported in the Journal of Clinical Oncology, Flaherty et al found that a shorter course of biochemotherapy consisting of cisplatin, vinblastine, dacarbazine, interleukin-2, and interferon alfa-2b produced better relapse-free survival, but not overall survival, and was associated with greater toxicity compared with a 1-year high-dose interferon alfa-2b regimen in patients with high-risk melanoma. The trial is a Cancer and Leukemia Group B, Children’s Oncology Group, Eastern Cooperative Oncology Group, and Southwest Oncology Group Intergroup study…

“In the trial, 402 patients aged ≥ 10 years with stage IIIA-N2a through IIIC-N3 melanoma were randomly assigned between September 2000 and November 2007 to receive biochemotherapy plus granulocyte colony-stimulating factor given every 21 days for three cycles (n = 199) or high-dose interferon alfa-2b intravenously 5 days per week for 4 weeks and subcutaneously three times per week for 48 weeks (n = 203). The coprimary endpoints were relapse-free survival and overall survival.

“The high-dose interferon and biochemotherapy groups were generally balanced for age (median, 48 and 46 years), sex (69% and 71% male), race/ethnicity (96% and 95% white), number of involved nodes (1–3 or satellite/in-transit only in 76% in both), nodal involvement (micrometasteses only in 43% and 44%), and ulceration (41% in both)…

“The investigators concluded: ‘Biochemotherapy is a shorter, alternative adjuvant treatment for patients with high-risk melanoma that provides statistically significant improvement in [relapse-free survival] but no difference in [overall survival] and more toxicity compared with [high-dose interferon].’ ”


Ipilimumab 'Greased the Wheel' for Newer Agents in Melanoma

The gist: In recent years, drugs that boost the immune system to fight cancer have taken center stage in melanoma treatment. These drugs are called immunotherapies. This article describes how the drug ipilimumab paved the way for more immunotherapy drugs for melanoma.

“There has been a paradigm shift in the treatment of melanoma, and immunotherapy now has center stage. There was a steep learning curve with the development of the first of these agents, ipilimumab (Yervoy, Bristol-Myers Squibb), but it has paved the way for a wave of new products.

“Ipilimumab was the first immune checkpoint inhibitor to be tested in patients, and the initial results showed responses were ‘quite remarkable,’ but the drug had unusual kinetics and unusual adverse events, commented Steven Bernstein, MD, from Bristol-Myers Squibb.

“Speaking at a company-sponsored satellite symposium here at the Society for Melanoma Research meeting, he emphasized that it was investigator experience with the drug that guided the protocols in clinical trials. Later, investigators also developed a new way of assessing immune responses as a better way of capturing the results that were being seen than the RECIST criteria that are used with chemotherapy.

“Recalling some of the lessons learned was Steven O’Day, MD, director of the Los Angeles Skin Cancer Institute, who was involved in the pivotal trial (N Engl J Med. 2010;363:711-723) that led to ipilimumab approval. This was the first time that a drug had been shown to improve overall survival in metastatic melanoma. That achievement was all the more remarkable considering that the response rate was only around 10%, he said.”


Immune System-Activating Drugs in Combination Treatments May Be Next Big Thing for Melanoma


Among solid tumors, the curative potential of immunotherapies has been explored most in melanoma. One reason for this is that melanoma tumors often contain so-called immune infiltrates—patches of T cells, the killer cells of the immune system. It seems that these fighter cells arrive at the ‘battlefield’ to target tumor cells for killing, but instead become ‘frozen,’ unable to attack.  How to activate the tumor-killing potential of T cells has been an area of intense and fruitful research, leading to the development of several immunotherapy drugs. Continue reading…


Old Cancer Drug Gets Fresh Look

“When Dave deBronkart was diagnosed with advanced kidney cancer in 2007, he learned about a treatment called high-dose interleukin-2 (IL-2) that fires up the body’s immune system to fight the disease. The response rate was not great — tumours shrank in only about 15% of patients. And as many as 4% of people died from the treatment. But some of those who responded survived for years or even decades.”

Editor’s note: IL-2 is an immunotherapy drug, meaning that it boosts a patient’s own immune system to fight cancer. It and other new immunotherapies are showing promise for patients across many different cancer types.


Old Cancer Drug Gets Fresh Look

“When Dave deBronkart was diagnosed with advanced kidney cancer in 2007, he learned about a treatment called high-dose interleukin-2 (IL-2) that fires up the body’s immune system to fight the disease. The response rate was not great — tumours shrank in only about 15% of patients. And as many as 4% of people died from the treatment. But some of those who responded survived for years or even decades.”

Editor’s note: IL-2 is an immunotherapy drug, meaning that it boosts a patient’s own immune system to fight cancer. It and other new immunotherapies are showing promise for patients across many different cancer types.


Old Cancer Drug Gets Fresh Look

“When Dave deBronkart was diagnosed with advanced kidney cancer in 2007, he learned about a treatment called high-dose interleukin-2 (IL-2) that fires up the body’s immune system to fight the disease. The response rate was not great — tumours shrank in only about 15% of patients. And as many as 4% of people died from the treatment. But some of those who responded survived for years or even decades.”

Editor’s note: IL-2 is an immunotherapy drug, meaning that it boosts a patient’s own immune system to fight cancer. It and other new immunotherapies are showing promise for patients across many different cancer types.


Immunotherapy, BRAF Inhibitor Sequence Affected Outcomes in Metastatic Melanoma

“Prior treatment with immunotherapy did not limit response to BRAF inhibitors among patients with metastatic melanoma, according to results of a retrospective study.

“However, patients who underwent initial treatment with BRAF inhibitors and subsequently received immunotherapy with ipilimumab (Yervoy, Bristol-Myers Squibb) demonstrated poorer outcomes, results showed.

“Patients with BRAF-positive metastatic melanoma have several treatment options, including BRAF inhibitors vemurafenib (Zelboraf, Hoffmann-La Roche) and dabrafenib  (Taflinar, GlaxoSmithKline), the MEK inhibitor trametinib (Mekinist, GlaxoSmithKline), and the immunotherapy agents ipilimumab and interleukin-2. Yet, there are limited data with regard to optimal sequencing, according to researchers.”


Personalized Vaccines May Boost Survival After Interleukin Treatment

High doses of interleukin-2 (IL-2) can shrink melanomas but only 15% of people are still alive five years after this treatment. Now, new research shows that giving people vaccines against their own tumors could boost survival after IL-2 treatment. In a study of 149 people with melanomas that had spread, those treated with both IL-2 and a personalized vaccine lived far longer than those treated with IL-2 alone (nearly 40 vs. 12 months, respectively). In addition, people were far more likely to be alive at five years when given the vaccine before IL-2 treatment than when the order was reversed (46% vs. 14%, respectively).


New Test May Predict Whether IL-2 Will Shrink Melanomas

While high-dose interleukin-2 (IL-2) shrinks about 15% of melanomas, this U.S. Food and Drug Administration (FDA)-approved immunotherapy comes at the high cost of seizures and other major side effects. Now, a new study suggests there may be a way to tell when people with melanoma are benefiting from IL-2, sparing those who are not from unnecessarily enduring the downside of this treatment. The researchers found that when people with melanoma were treated with high-dose IL-2, those who did not benefit also had high levels of a particular type of white blood cell. These cells are regulatory T cells that produce a protein called ICOS (inducible T cell costimulator), which is linked to suppression of the immune system.