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).
Cornelis “Kees” Melief, MD, chief scientific officer of ISA Pharmaceuticals in Leiden, the Netherlands, and colleagues reported these findings in Science Translational Medicine.
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 (NCT02128126) 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. Sci Transl Med. 2020;12:eaaz8235.