medwireNews: The addition of the oncolytic virus talimogene laherparepvec (T-VEC) to neoadjuvant chemotherapy may increase responses in women with nonmetastatic triple-negative breast cancer (TNBC), say phase 2 trial investigators.
Just under half of the participants of the single-arm study achieved a residual cancer burden of 0 (RCB0) with the combination of T-VEC and chemotherapy, which the researchers say is “above expected rates with chemotherapy alone in TNBC.”
They continue: “There is evidence of robust immune activation within the tumor and additional investigation of T-VEC in combination with current chemoimmunotherapy for TNBC is warranted.”
In the trial, 40 women with nonmetastatic, clinical stage T2–3, N0–2 disease received five intratumoral injections of T-VEC – the first in week 1 at a dose of 106 plaque-forming units and the rest at weeks 4, 6, 8, and 10 at 108 plaque-forming units – alongside neoadjuvant weekly paclitaxel 80 mg/m2 for 12 weeks. This was followed by four cycles of doxorubicin 60 mg/m2 and cyclophosphamide 600 mg/m2 given every 2 weeks and surgery.
As reported in Nature Medicine, the primary endpoint of RCB0 was achieved by 45.9% of the 37 evaluable participants, while the RCB0–1 rate was 65.0%.
At a median follow-up of 30 months, there were four incidences of distant breast cancer recurrence, with one leading to death from breast cancer. This gave a 2-year disease-free survival rate of 89%, report Hatem Soliman and colleagues from Moffitt Cancer Center in Tampa, Florida, USA.
They highlight that none of the recurrences occurred in patients who had an RCB of 0 or 1 after resection, and they “continue to do well.”
Soliman et al also note that the promising efficacy “was not accompanied by a significant increase in serious adverse events [AEs] or long-term autoimmune sequelae,” and the AE profile “did not differ significantly” from that expected with neoadjuvant chemotherapy.
The most common any-grade toxicities were anemia, fatigue, nausea, neuropathy, chills, and headaches, observed in 87.5%, 85.0%, 72.5%, 62.5%, 52.5%, and 50.0% of patients, respectively, but these were primarily of grade 1 or 2.
Neutropenia was the most common AE of grade 3–4, occurring at a rate of 17.5%, followed by anemia and fatigue, at 7.5% each.
The researchers report that four (10%) patients had venous thromboembolic events of grade 2–3, which was “slightly” higher than the expected rate of 6% with neoadjuvant chemotherapy.
And they conclude: “The intratumoral administration of oncolytic viruses is feasible in patients with neoadjuvant breast cancer and provides an ideal setting to investigate the ability of these agents to enhance the host immune antitumor response both locally and systemically.”
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Nat Med 2023; doi:10.1038/s41591-023-02210-0