Study shows promising benefit of combination therapy in CRPC patients

Multi-peptide vaccination therapy combined with the low-dose steroid drug dexamethasone shows promise in treating chemotherapy-naive castration resistant prostate cancer (CRPC) patients.

The study, which won the third prize for best abstract in oncology at the 28th European Association of Urology Congress held in Milan, Italy from 15 to 19 March, showed the promising benefit of this combination therapy in patients who are chemotherapy-naive or those not yet exposed to specific antigens.

"Results of our randomized prospective study suggest that multi-peptide vaccination therapy in combination with low dose dexamethasone has the therapeutic potential as a safe and efficient option for chemotherapy-na-ve CRPC patients," said lead study author Dr. Takahiro Kimura, of the Jikei University School of Medicine, Dept. of Urology, Tokyo, Japan.

Since immunotherapy does not have a strong ability to decrease tumour burden, it is considerably difficult to evaluate the full extent of a significant therapeutic effect with peptide vaccines, explained Kimura. "Taking this into consideration, the present evidence is promising," he said.

The researchers have previously developed MHC class-I restricted peptide vaccines for prostate cancer and carried out a phase 1 trial to assess safety and immunological evaluation. In the present study, Kimura and his colleagues conducted a randomized phase 2 study to evaluate the efficacy of peptide vaccine therapy for chemotherapy na-ve CRPC patients.

Early stage CRPC (PSA<10ng/ml) patients were randomized to two treatment groups; peptide vaccine with low dose (1mg/day) dexamethasone (Dx), while the other group were given low dose Dx alone. The patients were vaccinated subcutaneously with 3 mg of selected peptides (max. 4 kinds) six times at two weeks interval. Dx 1mg/day p.o. was started on the first day of peptide vaccination. Toxicity assessment, immunological and clinical responses were investigated every three months. The primary endpoint of the study is progression-free survival including serum PSA.

Kimura said that although percentage PSA decline is the same in both vaccination/dexamethasone and dexamethasone alone group, PSA-PFS was significantly longer (p<0.0008) in the vaccination group.

"This means that the anti-tumour immune response may play an important role in suppressing disease progression. This therapeutic strategy using peptide vaccines is likely to be comparable as that from currently developed anti-androgenic agents such as abiraterone acetate, MDV3100," Kimura noted.

Castration resistant prostate cancer is a difficult patient group to manage since although a number of therapeutic modalities have been developed, none have lived up to the full expectations and treatment options remain limited.

Kimura added that although the concept of immunotherapy for cancer is not new, recent technological advances have opened new avenues to explore and optimize peptide-based immunotherapy.

"Since the anti-tumour effects of peptide vaccination are driven by different mechanisms as those from ADT and chemotherapy, we may circumvent many of the pitfalls experienced with the current therapies. We believe that this treatment approach will be key in order to achieve a breakthrough as a new therapeutic option for CRPC," he said.