Personalized cell therapy shows promise in metastatic breast cancer
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Three of six women with metastatic breast cancer who received investigational tumor-infiltrating lymphocytes plus pembrolizumab demonstrated tumor reductions greater than 50%, according to phase 2 study results.
One patient achieved a complete response and did not require further treatment or surgical intervention, findings from the ongoing NCI-led study showed.
Background
The study is designed to evaluate use of tumor-infiltrating lymphocytes (TILs) for patients with metastatic epithelial cancers, including breast cancer.
“Nearly all who develop metastatic breast cancer will ultimately die [of] their disease,” researcher Steven A. Rosenberg, MD, PhD, chief of the surgery branch and head of the tumor immunology section of NCI’s Center for Cancer Research, told Healio. “We can prolong survival [for] these patients, but the best of surgery, radiation and chemotherapy cannot cure them.”
Chimeric antigen receptor T-cell therapy targets a unique antigen found on the surface of certain cancers. TILs have been effective where other cell therapies have failed because the highly personalized treatment is based on the neoantigens specific to a patient’s tumor, Rosenberg said.
Every patient in the NCI study had a unique set of cancer mutations, Rosenberg said.
“Regardless of whether it is found in the breast, colon or elsewhere, solid cancer antigens tend to be unique, and they are unique because each of the antigens are the product of mutations that occur within the cancer itself,” he told Healio. “Ironically, it is those very cancer mutations that represent the possible Achilles’ heel of solid cancers when it comes to use of immunotherapy.”
Methodology
The study included 42 patients (median age, 49 years; range, 35-67) with hormone receptor-positive metastatic breast cancer.
More than two-thirds of patients had TILs generated from resected tumors that recognized at least one neoantigen. Researchers identified eight patients clinically eligible for the investigational therapy.
Six patients subsequently received a TIL infusion followed by up to four doses of the anti-PD-1 therapy pembrolizumab (Keytruda, Merck).
Key findings
Three of the six patients achieved an objective response to TIL therapy plus pembrolizumab. One patient who achieved a complete response remained cancer free more than 5.5 years after her infusion.
Another patient had an objective response that lasted 10 months and resulted in 69% tumor regression. The patient had one remaining tumor resected and had no evidence of disease or further metastases at data cutoff.
A third patient had an objective partial response that lasted 6 months and resulted in a 52% reduction in tumors. The patient developed disease in an axillary node but continued experiencing breast tumor regression at 9 months after infusion, at which time she had all remaining tumors surgically resected. She remained disease free 31 months after TIL infusion.
Clinical implications
Despite the small patient population, Rosenberg said the findings demonstrate patients with metastatic breast cancer can achieve considerable reductions in tumor volume despite disease progression while receiving standard-of-care treatments.
“This study shows that certain breast cancers can be susceptible to immunotherapy,” he added.
The NIH expects its new cell manufacturing facility to be fully operational soon, Rosenberg said. This will allow his group to enroll and treat more patients with TILs as part of the phase 2 study.
His group is enrolling patients with metastatic breast cancer, and he encouraged clinicians or patients interested in being evaluated for the study to email their nurse referral system at irc@nih.gov.
"I expect there to be a substantial increase in the number of patients we will be treating over the next several months,” Rosenberg said.
For more information:
Steven A. Rosenberg, MD, PhD, can be reached at Center for Cancer Research, National Cancer Institute, Building 10 — Hatfield CRC, Room 3-3940, Bethesda, MD 20892-1201; email: sar@nih.gov.
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