Imfinzi-Novel Drug Combination Elicits Effective Responses in a Group of Patients With Metastatic Sarcomas

The use of two immune checkpoint inhibitors in combination with each other was associated with effective outcomes in a group of patients with advanced or metastatic soft tissue or bone sarcomas, according to recently published findings in Lancet Oncology.

The patient population enrolled onto the trial included individuals for whom traditional treatments such as chemotherapy have not been effective.

The two drugs examined in this study, Imfinzi (durvalumab) and tremelimumab, are an anti-PD-1 and an anti-CTLA-4 antibody, respectively. This means each medication is designed to increase the patient’s immune system response by specifically blocking proteins that slow down the body’s T cells. Cytotoxic (meaning toxic to living cells) chemotherapy is a common treatment for a metastatic sarcoma, which already mimics the natural immune defense of cytotoxic T cells.

Patients enrolled onto the single-center trial were grouped together based on the type of tumor they had. They first received 75 milligrams (mg) of tremelimumab and 1500 mg of Imfinzi an hour later once a week for four weeks. After the first month of combination therapies, patients were treated exclusively with Imfinzi for up to eight weeks or until their disease progressed or treatment became too harmful to living cells.

At a median follow-up of 37.2 months, 51 of the 57 patients who were treated with the Imfinzi and tremelimumab combination either died or had disease progression.

The 12-week progression-free survival (defined as evidence of treatment response or stable disease at 12 weeks after the beginning of treatment) rate among all enrolled patients was 49%.

Moreover, the median progression-free survival (length of time a patient survives during and after treatment without disease progression) was 2.8 months.

Of note, 10 of the patients included in the study had alveolar soft part sarcoma, which is a cancer that may come from soft tissue such as muscle, fat or nerves. The findings showed that this subgroup of patients achieved a progression-free survival of 80% at 12 weeks, which was the highest among patient subgroups.

“There are certain sarcoma subtypes where (oncologists) run out of options very quickly, we don’t have a lot of options for them, and some (patients) don’t respond to chemotherapies,” Dr. Neeta Somaiah, the deputy department chair of the Department of Sarcoma Medical Oncology at The University of Texas MD Anderson Cancer Center in Houston, said in an interview with CURE®. “One that doesn’t respond to chemotherapies but really responds to immune checkpoint blockades is alveolar soft-part sarcoma, so there’s a great benefit to those that need a standard of care.”

As of April 2020 (the time the data were last collected), the median overall survival (time from either diagnosis or start of treatment that half of the patients in the study are still alive) was 65% after one year and 49% after two years.

Somaiah urged patients with advanced or metastatic sarcoma to speak with their care teams to see if they may be candidates to receive immune checkpoint inhibitors.

“Patients should consult with their oncologist to see if their sarcoma subtype lends itself to a response with immune checkpoint blockade either based on the subtype or based on any molecular characteristics identified in profiling,” she said. “It is not applicable to all patients, but it warrants discussion with a care team.”

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