Oncolytic virus therapy may boost antitumor response in triple-negative breast cancer
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The oncolytic virus talimogene laherparepvec combined with neoadjuvant chemotherapy appeared safe and effective for women with early-stage triple-negative breast cancer, according to phase 2 study results published in Nature Medicine.
The findings support further evaluation of combination therapy with talimogene laherparepvec (Imlygic, Amgen) — a modified herpes simplex virus-1-based oncolytic immunotherapy — in a larger randomized trial, researchers concluded.
Rationale and methodology
“We have researched various ways to render triple-negative breast cancer tumors more susceptible to patients’ immune cells for several years,” Hatem Soliman, MD, medical director of the clinical trials office at H. Lee Moffitt Cancer Center and Research Institute, told Healio. “Data from our research and others have shown that high-grade breast tumors, such as triple-negative breast cancer, may be susceptible to the immune-activating effects of oncolytic viruses attacking cancer cells.”
Moreover, Soliman said it has been suggested that oncolytic viruses given during systemic chemotherapy may have an additive or synergistic effect against tumor cells, thereby eradicating the cancer more effectively.
“We therefore proposed an investigator-initiated trial at Moffitt Cancer Center to study the effects of intertumoral talimogene laherparepvec during neoadjuvant chemotherapy,” he said.
The single-arm phase 2 trial included 37 women (median age, 49 years; 73% white) with stage II to stage III triple-negative breast cancer. Trial participants received five infusions of talimogene laherparepvec, also known as T-VEC, combined with paclitaxel, followed by doxorubicin and cyclophosphamide and surgery.
“The neoadjuvant setting is an ideal one to test an oncolytic virus because we have easy access to the tumor, an immune system that has not been suppressed by extensive prior therapy, and a way to get an early read-out on efficacy by looking at pathologic response rates,” Soliman said.
Residual cancer burden (RCB) index rate of 0 served as the primary outcome. Secondary outcomes included RCB rate of 0 to 1, recurrence rate, toxicity and immune correlates.
Median follow-up was 30 months.
Findings
Results showed the oncolytic virus combination therapy induced RCB 0 pathologic complete responses in 16 of 37 women, for an estimated 45.9% (90% CI, 32-54) pathologic complete response rate.
Eight other women had RCB 1 minimal residual disease, for an RCB 0-to-1 descriptive rate of 65% (95% CI, 50-82).
“We also observed excellent survival with only four patients who experienced disease recurrence, for a DFS rate of 89% with no recurrences among women who achieved a complete or near complete response,” Soliman said.
The most common adverse events with talimogene laherparepvec included fever, chills, headache, fatigue and injection site pain.
One of four women who experienced distant breast cancer recurrence died of her disease, and no DFS events occurred among women with RCB 0-to-1 rates.
Moreover, 14% of women did not complete the entire chemotherapy sequence due to severe neuropathy in one patient and chemotherapy-associated adverse events in three patients.
“Talimogene laherparepvec combined with neoadjuvant chemotherapy led to a significant increase in the immune activation within the tumor microenvironment in ways that are different from what would be expected with chemotherapy alone,” Soliman said. “The therapy was feasible with no significant autoimmunity noted and is an exciting way to boost the antitumor immune response during neoadjuvant therapy without increasing immune-related toxicities among women with triple-negative breast cancer.”
Implications
Based on the findings, the novel oncolytic virus therapy should be added to standard pembrolizumab (Keytruda, Merck) plus chemotherapy and tested in a larger randomized trial to demonstrate that the therapy can boost complete response and cure rates vs. the pembrolizumab regimen alone, Soliman told Healio.
“We should also continue studying biomarkers to learn how we can better select patients for this treatment and overcome resistance,” he said. “The addition of oncolytic virus plus checkpoint therapy may allow for testing de-escalation of chemotherapy while maintaining high cure rates for women with early-stage disease.”
For more information:
Hatem Soliman, MD, can be reached at hatem.soliman@moffitt.org.
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