Axalimogene filolisbac cancer vaccine benefits cervical cancer patients
The experimental cancer vaccine axalimogene filolisbac (Advaxis) has the potential to extend overall survival in cervical cancer patients, according to data from a recent clinical trial. The GOG-0265 study evaluated the treatment in subjects with persistent or recurrent metastatic squamous or non-squamous cell cervical carcinoma. The U.S. Food and Drug Administration (FDA) put the trial on hold following a death of a patient. After the hold was lifted, analysis of the 24 enrolled patients showed overall survival after one year of 37.5%.
Combined with similar earlier results from 26 subjects, it translates into an estimated 50% increase in 1-year survival rate for the vaccine cohort. The treatment had some serious side effects, with two patients experiencing grade-4 adverse events.
Axalimogene filolisbac is a vaccine specific for cancers caused by HPV. It is a live attenuated Listeria monocytogenes engineered to secrete HPV-16 E7 protein. It is being investigated as a treatment of head-and-neck and anal cancers and as an adjuvant in cervical cancer therapy.
Unvaccinated adults cost the American economy >$7 billion in 2015
Americans who do not comply to vaccine recommendations by the Centers for Disease Control and Prevention (CDC) cost the U.S. economy ∼$7.1 billion in 2015, according to an estimate published in Health Affairs.1 About 80% of these costs were associated with influenza, followed by pneumococcal disease and shingles. The study did not take into account the cost of vaccines and immunization programs.
There are 10 vaccines protecting against 14 diseases on the CDC list. The influenza vaccine was administered to less than half of eligible subjects (anyone older than 6 months) during the 2015–6 season.
1.Ozawa S, Portnoy A, Getaneh H, Clark S, Knoll M, Bishai D, Yang HK, Patwardhan PD. Modeling The Economic Burden Of Adult Vaccine-Preventable Diseases In The United States. Health Aff 2016; doi: 10.1377/hlthaff.2016.0462
Checkpoint inhibitors approved for NSCLC, promising in bladder cancer
The immunotherapeutic pembrolizumab (Keytruda, Merck) was approved by the FDA as a first-line treatment in metastatic non-small cell lung cancer (NSCLC) patients with high levels of PD-L1 marker. The MAb works by blocking the PD-1 pathway used by some cancers to inhibit T-cell responses.
Atezolizumab (Tecentriq, Roche) is another checkpoint inhibitor approved by the FDA for the treatment of metastatic NSCLC in patients who have not responded to previous chemotherapy. The PD-L1-targeting MAb extended life prospects by 4.2 months compared to docetaxel in a large-scale Phase 3 OAK trial. This was irrespective of the PD-L1 blood levels. Atezolizumab is also under investigation as a first-line therapy and in combination with other treatment options.
Pembrolizumab also showed promising results in the Phase 2 Keynote-052 trial in cisplatin-ineligible subjects with metastatic or locally advanced bladder cancer. The treatment was well tolerated in the first 100 patients with an objective response rate of 24%.
Another PD-1 inhibitor nivolumab (Opdivo, BMS) brought clinical benefits to 265 chemo-refractory bladder cancer patients in the Phase Check-Mate 275 study, in which the median duration of response had not been reached after seven months.
Women vaccinated against HPV might need less frequent cervical cancer testing
Women vaccinated with the 9-valent HPV vaccine could have as few as four screens for cervical cancer starting at age 30–35. A cost-effectiveness study published in Journal of the National Cancer Institute1 has shown that intensive screening of vaccinated women brings excess costs with little or no health benefits. Screening for cervical cancer is recommended every three years starting at age 21.
Assuming full compliance to the HPV immunization schedule, women vaccinated with the 2-valent or 4-valent vaccines would need a test every five years from age 25–30. These vaccines target two HPV strains responsible for 70% of cervical cancers, 90% for HPV-9.
1.Kim JJ, Burger EA, Sy S, Campos NG. Optimal Cervical Cancer Screening in Women Vaccinated Against Human Papillomavirus. J Natl Cancer Inst 2016; 109(2)
Genital herpes immunotherapy strongly immunogenic in a Phase 2 trial
The GEN-003 genital herpes immunotherapy (Genocea) elicited strong CD4+ as well as antibody production in 310 subjects enrolled in a Phase 2 clinical trial. At the best dose, viral shedding and the rate of genital lesions were reduced by 2/3. 30% of patients remained without lesions after one year.
GEN-003 contains two HSV-2 antigens together with the Matrix-M2 adjuvant. Genital herpes affects >400 million people worldwide and can be transmitted even when asymptomatic. There is no cure available.
CDC now recommends two doses of HPV vaccine for children
Two doses instead of three will be sufficient to complete the recommended HPV immunization schedule in U.S. children aged <15 years. The new CDC recommendation follows clinical trial data suggesting that two doses or three doses in subjects aged 9–14 elicit comparable antibody responses. Adolescents 15–26 years of age are still recommended to get three doses of HPV vaccine.
The CDC hopes to encourage completion, which is estimated at only 40% for boys and 21% for girls in the U.S., short of the government's 2020 target of 80% for both sexes.
Clinical trials start for a combination immunotherapy in head-and-neck cancer patients
HPV-positive head-and-neck cancer patients who failed standard therapy will be enrolled to Phase 1/2 study of a combination immunotherapy planned for 2017. The PD-L1 inhibitor MAb avelumab (Merck) and the HPV antigens-expressing vaccinia-vector-based vaccine TG4001 (Transgene) target different stages of the immune response and thus could improve efficacy by eliminating tumor cells.
“HPV-induced head and neck cancers are currently treated with the same regimen as non-HPV-positive […] tumors. However, their different etiology clearly suggests that differentiated treatment approaches are needed for HPV-positive patients,” study leader Christophe Le Tourneau of Institut Curie said in a statement.
Immunotherapy combination for treatment of prostate cancer enters Phase 2
A Phase 2 trial of ipilimumab (Yervoy, BMS) and Prostvac (Bavarian Nordic) immunotherapies is enrolling 75 prostate cancer patients. They will be divided into 3 groups, ipilimumab, Prostvac or both, and tested for antitumor T-cell responses and immunologic infiltration. The combination provided survival advantage to subjects with metastatic prostate cancer in a previous Phase 1 study.
Ipilimumab is an anti-CTLA-4 MAb designed to block an immune-suppression pathway, and Prostvac is a vaccine containing a prostate-specific antigen.
Cancer vaccine plus immunotherapy are tested in Phase 1/2 in lung cancer patients
The PD-1 inhibitor nivolumab (Opdivo, BMS) is being tested in a Phase 1/2 study in combination with the cancer vaccine CIMAvax-EGF in subjects with advanced NSCLC. Up to 90 patients are being enrolled at the Roswell Park Cancer Institute.
The target of CIMAvax-EGF is epidermal growth factor, which tumors use to boost their growth. The vaccine improved survival of lung cancer patients with minimal side effects in a previous Phase 3 trial.
New quadrivalent influenza vaccine approved in the U.S.
The FDA has approved the Flublok quadrivalent influenza vaccine (Protein Sciences). In a large-scale trial with people aged >50 years, the vaccine had a 40% higher rate of immunological efficacy than another licensed vaccine.
Flublok contains three times as much viral antigen, and is therefore suitable for seniors and immunocompromised subjects. It also is suitable for people allergic to eggs, since it contains hemagglutinin harvested from insect cells without a need for egg-based production.