Study: No survival benefit seen in combination chemoimmunotherapy for aggressive melanoma

September 1, 2007

The combination of chemotherapy and immunotherapy has gained some attention as a potential means for improving treatment results in patients with metastatic melanoma, but a recent review of literature indicates that the combination therapy only increases toxicity in patients while offering no improvement in survival rates The review of 18 randomized studies involving 2,625 patients did show an increase in increase in objective response rates in patients treated with chemoimmunotherapy, compared to those treated with chemotherapy, but there was no difference in survival benefit, whereas the combination treatment resulted in increased hematological and non-hematological toxicities.

Key Points

Sao Paulo, Brazil - In the ongoing search for an effective systemic treatment for metastatic melanoma, the combination of chemotherapy and immunotherapy has gained some attention as a potential means for improving treatment results.

But a recent review of literature suggests that the combination therapy only increases toxicity in patients while offering no improvement in survival rates.

Researchers with the oncology department with Cidade Universitaria of State University of Campinas in Sao Paulo, Brazil, reviewed 18 randomized studies involving 2,625 patients that compared the use of chemotherapy versus chemotherapy and immunotherapy with interferon-alpha or interleukin-2 in patients of any age who were diagnosed with metastatic melanoma [Database Syst Rev. 2007 Jan 24;(1):CD005413].

While the findings did show an increase in objective response rates in patients treated with chemoimmunotherapy, compared with those treated with chemotherapy, there was no difference in survival benefit.

No statistical significance

"There was no statistically significant difference in survival between chemoimmunotherapy and chemotherapy, with a hazard ratio of improved survival of 0.89 (95 percent CI 0.72 to 1.11, p =0.31) in favor of chemoimmunotherapy," according to the study.

"In other words, overall survival was slightly lower in the chemoimmunotherapy group, but this was not statistically significant."

Furthermore, increased hematological and nonhematological toxicities were seen among patients treated with the chemoimmunotherapy.

"We found evidence of an increase of objective response rates in people treated with chemoimmunotherapy, in comparison with people treated with chemotherapy," the authors write.

Specifically, the combined analysis of available studies on chemoimmunotherapy use showed an increase of tumor shrinkage from 18 percent to 27 percent, Andre Sasse, M.D., Ph.D., a lead author on the study, tells Dermatology Times.

"Nevertheless, the impact of this increased response rate was not translated into a survival benefit," the authors write. "We found no difference in survival to support the addition of immunotherapy to chemotherapy in the systemic treatment of metastatic melanoma, with a hazard ratio of 0.89 (95 percent CI 0.72 to 1.11, p=0.31)."

Adverse effects reported from the therapy include flu-like syndrome, fever, headache and myalgia and, less commonly, nausea and vomiting, hypotension, skin rash and diarrhea.

The chemoimmunotherapy approach stems from some reports suggesting that chemotherapeutic agents administered in combination with IL-2 or IFN could improve response rates, with complete response rates in 10 percent to 20 percent of people (Legha, 1998; Richards, 1992), as well as help to increase median survival (Falkson, 1991).

Based on these results, chemoimmunotherapy is currently practiced in some facilities as a first-line treatment for advanced (stage IV) melanoma (Kadison, 2003; Keilholz, 2002); however, it is still considered an experimental therapy by others.

Some melanoma doctors, in particular, have turned to the therapy as a possible treatment option, despite weak evidence of its efficacy.

"The adoption of this kind of treatment depends mainly on the doctor's beliefs, and melanoma specialists tend to prescribe more often than community doctors," Dr. Sasse says.

Grasping at straws

In addition, since metastatic melanoma has such a poor prognosis, with median survival at approximately eight months and less than 5 percent of such patients surviving for more than five years, that doctors will often go out on a limb to try to find an effective treatment, he adds.

"Some doctors use their experience and anecdotal reports in addition to scientific information with low quality to inform patients and perform their prescriptions," he says. "Sometimes they minimize the risks and toxicities but overestimate the benefits."

But with no strong evidence of improvement in survival rates, there is little justification in subjecting patients to the therapy's adverse effects, Dr. Sasse adds.

"The adverse effects from chemoimmunotherapy are very common, reaching more than 50 percent of the patients," he says. "But the high incidence of adverse effects is the main reason for not prescribing this kind of treatment."

For more information:
Cochrane Database Syst Rev.
2007 Jan 24;(1):CD005413