Longer survival was observed in women who had a stronger immune response to an investigational human papillomavirus (HPV) vaccine while treated with standard chemotherapy for advanced, metastatic, or recurrent cervical cancer.
The results, from a phase 1/2 study, showed that women with a vaccine-induced immune response higher than the median had a median overall survival of 16.8 months, compared with a median overall survival of 11.2 months for women with an immune response lower than the median (hazard ratio, 0.491; P = .012).
, chief scientific officer of ISA Pharmaceuticals in Leiden, the Netherlands, and colleagues reported these findings in .
The researchers previously evaluated the HPV16 vaccine, ISA101, in combination with carboplatin and paclitaxel in a pilot study. Results showed that carboplatin and paclitaxel reduced abnormally high numbers of immunosuppressive myeloid cells, which allowed for “much stronger” ISA101-induced tumor immunity.
To investigate further, the researchers tested the chemotherapy-ISA101 combination in a phase 1/2 study () of 79 women with advanced, metastatic, or recurrent HPV16-positive cervical cancer.
The patients received the vaccine 2 weeks after starting the second, third, and fourth cycles of chemotherapy. They received various doses of the vaccine (20, 40, 100, or 300 mcg) with or without pegylated type 1 interferon (1 mcg/kg body weight).
“ISA101 was generally safe and well tolerated in that its safety profile was not different from chemotherapy alone,” Dr. Melief and colleagues wrote.
Chemotherapy-associated adverse events occurred in 98.9% of patients, with more than 80% of patients reporting adverse events possibly related to the vaccine or interferon-alpha. However, less than 16% of patients withdrew from the study because of an adverse event.
Of the 72 patients evaluable for efficacy, 43% experienced tumor regression, and 43% had stable disease. The researchers observed regression of the target lesion in 29 of 59 patients with a measurable target lesion.
The team noted that, since all patients received chemotherapy, it is “difficult to interpret short-term clinical outcomes as being due to chemotherapy alone or to the combination,” although they noted that the use of interferon-alpha did not seem to provide any additional benefit.
“Eleven of 14 patients still alive at the end of the study displayed a strong vaccine-induced response and included 9 patients with FIGO stage IVa/IVb cancer who had a mean OS [overall survival] of 3 years,” the researchers noted.
Considering that patients with higher vaccine-induced immune responses lived longer, the researchers concluded that “chemoimmunotherapy can be exploited to the benefit of patients with advanced cancer based on a defined mode of action.”
This trial was funded by ISA Pharmaceuticals and a Dutch Cancer Society grant. Investigators disclosed relationships with ISA Pharmaceuticals and other companies.
SOURCE: Melief CJM et al. .