In the Journals

CTLA-4 therapy yields durable responses in some patients with advanced melanoma

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October 7, 2015

Tremelimumab conferred durable objective responses that lasted 12 years or more in patients with advanced melanoma, according to results of a retrospective, multi-institutional study.

Tremelimumab (AstraZeneca) — an anti-cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) antibody that binds to a T-cell receptor to block stimulatory B7 ligands — activates the immune system and drives T-cell activity against cancer.

Zeynep Eroglu

Zeynep Eroglu

Although newer checkpoint inhibitors — such as PD-1 and PD-L1 antibodies — appear to have greater response rates, long-term follow-up is not yet available for these therapies. Anti-CTLA-4 agents like tremelimumab are currently being evaluated in combination with other checkpoint inhibitors.

Before those data mature, Zeynep Eroglu, MD, a medical oncologist at the H. Lee Moffitt Cancer Center in Tampa, and colleagues sought to evaluate long-term survival in patients with advanced melanoma treated with tremelimumab.

“It was gratifying to observe that a subset of patients with advanced melanoma, enrolled in the first tremelimumab trials as far back as 2002, could still be alive and doing well so many years later,” Eroglu told HemOnc Today. “These patients who are alive and disease free over a decade could essentially be considered cured from their melanoma.

“Not surprisingly, this was much more likely to happen for the patients whose tumors had objective responses to tremelimumab; in the unlikely instances these patients had eventual tumor progression, they were likely to became disease free again after surgical resection and/or repeat tremelimumab therapy.”

Eroglu and colleagues retrospectively reviewed the records of 143 patients who were enrolled in one of four phase 1 or phase 2 tremelimumab trials between January 2002 and May 2008.

In these trials, tremelimumab dosage ranged from 0.01 mg/kg to 15 mg/kg every 3 months. The median OS was 13 months (95% CI, 10-16.6 months), but ranged from less than 1 month to more than 12 years.

An objective response rate was identified in 15.6% (95% CI, 10-22.7) of the patients and the median duration of response of 6.5 years (range, 3 to 136+ months). Only two of 28 patients (7.1%) who received 0.01-mg/kg to 6-mg/kg doses achieved a response compared with 20 of 114 patients (18%) who received 10-mg/kg or 15-mg/kg doses, although this difference did not reach statistical significance.

Of the patients who had an objective response, 31.8% had stage IIIC disease. These patients appeared more likely to have a response compared with patients with stage IV melanoma (P = .004).

The estimated 5-year survival rate was 20% (95% CI, 13-26), and the estimated 10- and 12.5-year survival rates were 16% (95% CI, 9-23).

Of the 22 patients who achieved objective responses, 15 had responses lasting for 5 years. Only one patient who achieved a complete response relapsed but remains alive 11 years later after undergoing surgical resection and reinduction with tremelimumab.

“Similar results have also been observed with much larger groups of patients treated with ipilimumab [Yervoy, Bristol-Myers Squibb], and the hope is that even better long-term outcomes will be seen with anti–PD-1/PD-L1 antibodies, given their much higher tumor response rates compared to anti–CTLA-4 antibodies,” Eroglu said. “Similar to ipilimumab, tremelimumab is currently being tested in trials combined with other immunotherapeutics in metastatic melanoma and other cancer types, and may become a treatment option as part of a combination therapy for these patients.”   – by Anthony SanFilippo

Disclosure: Please see the full study for a list of all the researchers’ relevant financial disclosures.

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