Immunotherapy Effective in Alveolar Soft Part Sarcoma
January 9, 2019, by NCI Staff
People with advanced alveolar soft part sarcoma (ASPS), a rare cancer, appear to benefit from a type of immunotherapy called an immune checkpoint inhibitor, according to results from a small clinical trial.
Few treatments tested in the past in people with ASPS have shown any effect. The exception has been a class of drugs called tyrosine kinase inhibitors (TKIs), which include sorafenib (Nexavar)and cediranib (Recentin). Although some patients’ tumors shrink following treatment with these drugs, most cancers eventually stop responding to treatment.
In the new NCI-led trial, tumors either shrank or stopped growing following treatment with the checkpoint inhibitor atezolizumab (Tecentriq).
“For patients whose disease has metastasized, it’s exciting that there may now be a whole new class of drugs that have [anticancer] activity,” said Scott Schuetze, M.D., Ph.D., who specializes in treating sarcomas at the University of Michigan but was not involved in the study.
The trial results were presented November 16 at the 2018 annual meeting of the Connective Tissue Oncology Society (CTOS).
Striking People in their Prime
ASPS is extremely rare, with fewer than 100 cases diagnosed each year in the United States. It starts in soft-tissue cells, such as muscle or fat. Unlike most other cancer types, it usually affects younger people: women and men in their 20s, 30s, and 40s, explained Dr. Schuetze.
“It tends to hit people who are in their prime” he said. “That obviously has a big impact not only on health but on people’s ability to advance in their career and plan having a family.”
The mainstay treatment for ASPS is surgery, sometimes combined with radiation therapy. But ASPS usually spreads to other parts of the body early in its course. Metastatic ASPS tumors, most often found in the lung or brain, tend to be slow-growing (indolent) but eventually start to cause symptoms. Metastatic ASPS is always fatal, said the trial’s co-leader, Alice Chen, M.D., head of the Developmental Therapeutics Clinic in NCI’s Division of Cancer Treatment and Diagnosis (DCTD).
Chemotherapy is not effective in patients with metastatic ASPS. Over the last decade, however, small studies have shown that TKIs can sometimes slow the growth of metastatic disease. One TKI, pazopanib (Votrient), has received Food and Drug Administration approval for treating soft-tissue sarcomas.
But given the limited effectiveness of pazopanib and other TKIs in ASPS, researchers have been studying other possible therapies, including immunotherapies.
Recent studies in mice conducted by the NCI-sponsored Pediatric Preclinical Testing Consortium suggested that atezolizumab might suppress the growth of ASPS.
“There have been very few sarcoma subtypes that respond to immunotherapy, but ASPS is one type that appears to be responsive,” said trial co-leader Geraldine O’Sullivan Coyne, M.D., Ph.D., who presented the trial results at the CTOS meeting.
ETCTN Advancing Clinical Trials for Rare Cancers
The ETCTN was created by NCI to speed clinical trials of investigational drugs in rare cancer types in which there is unmet need for new treatments.
The ETCTN has participating investigators at more than 50 hospitals and treatment centers across the United States and Canada. This not only allows for rapid accrual for trials in rare cancers, “it allows patients to stay closer to home when they’re getting treatment,” said Dr. O’Sullivan Coyne.
NCI’s Developmental Therapeutics Clinic (DTC), which led the trial of atezolizumab in alveolar soft part sarcoma, is a member of the ETCTN. The DTC focuses on rationally developing new drugs and drug combinations that target specific abnormalities in tumors.
Better than Expected Responses
Based on this research, Dr. O’Sullivan Coyne and Dr. Chen launched a phase 2 clinical trial of atezolizumab in metastatic ASPS in early 2017. Because of the disease’s rarity, they ran the trial through NCI’s Experimental Therapeutics Clinical Trials Network (ETCTN) (see sidebar).
Overall, 24 patients with metastatic ASPS enrolled in the trial. Early results from the first 22 patients were presented at the CTOS meeting.
Most participants had received prior treatments for metastatic disease, including TKIs. The responses to atezolizumab “were [greater] than we anticipated,” said Dr. O’Sullivan Coyne. Eight out of the 19 participants who had been receiving atezolizumab for long enough to be assessed had their tumors shrink (a partial response). Tumors stopped growing in another nine participants (stable disease).
Several of these responses had lasted for more than a year at the time of data analysis. Participants whose tumors are responding to atezolizumab will be allowed to keep taking it as long as their tumors continue to respond, explained Dr. O’Sullivan Coyne.
No serious side effects related to atezolizumab occurred during the trial. One participant experienced a bone fracture that may have been due to the study drug.
The researchers hope to expand the trial to include more patients with ASPS, as well as patients with two other rare sarcoma subtypes.
Future Research Directions
In the future, “these results may encourage investigators to consider [patients with] ASPS for other immunotherapy trials. And I think it will also lead to more trials [just] in this rare tumor subtype,” said Dr. O’Sullivan Coyne, who received the CTOS Young Investigator Award for her work on the study.
At the CTOS meeting, researchers from several different countries expressed interest in testing atezolizumab to treat ASPS, including in combination with other therapies as well as in different sequences of administration, Dr. Chen noted.
Dr. Schuetze agreed that studies are needed to clarify the best order of treatment—whether giving a TKI or immunotherapy first might provide better outcomes.
“There's a lot to learn about what might be the right sequence,” he added. “But because it is such a rare disease, the challenge will be prioritizing the [research] questions and making sure that trials aren't competing against each other for participants,” Dr. Schuetze concluded.
.png)
No hay comentarios:
Publicar un comentario