Nivolumab beneficial for cancer patients in two late-stage trials
The PD-1 monoclonal antibody (MAb) checkpoint inhibitor nivolumab (Opdivo, BMS) improved prospects of patients with kidney cancer and non-small cell lung cancer (NSCLC), according to two Phase 3 studies published in The New England Journal of Medicine.
In >800 subjects with advanced renal-cell carcinoma, half received nivolumab and half received standard-of-care everolimus.1 The response rate was 25% for the nivolumab cohort and 5% for the control group, and median overall survival was 25 and <20 months, respectively. Nivolumab also was safer with 19% of patients reporting adverse events compared to 37% in everolimus group.
“It is exciting to see the outcome of this study, as the results are significant and clinically meaningful to patients and healthcare professionals alike,” principal investigator Padmanee Sharma of the MD Anderson Cancer Center in Houston said in a press release. “They are likely to change the treatment of patients with advanced kidney cancer, whose disease has progressed on prior treatment.”
In the second study, nivolumab was compared with the chemotherapy drug docetaxel in nearly 600 advanced NSCLC patients.2 The immunotherapeutic MAb extended median overall survival by almost 3 months to 12.2 months. The overall survival rate at one year was 51% for nivolumab-treated subjects vs. 39% for the control group, while at 18 months it was 39% and 23%, respectively. Again, adverse events were less frequent in the nivolumab group: 10% versus 54%.
1. Motzer RJ, Escudier B, McDermott DF, George S, Hammers HJ, Srinivas S, Tykodi SS, Sosman JA, Procopio G, Plimack ER, Castellano D, Choueiri TK, Gurney H, Donskov F, Bono P, Wagstaff J, Gauler TC, Ueda T, Tomita Y, Schutz FA, Kollmannsberger C, Larkin J, Ravaud A, Simon JS, Xu LA, Waxman IM, Sharma P; CheckMate 025 Investigators. Nivolumab versus Everolimus in Advanced Renal-Cell Carcinoma. N Engl J Med 2015; doi: 10.1056/NEJMoa1510665
2. Borghaei H, Paz-Ares L, Horn L, Spigel DR, Steins M, Ready NE, Chow LQ, Vokes EE, Felip E, Holgado E, Barlesi F, Kohlhäuf M, Arrieta O, Burgio MA, Fayette J, Lena H, Poddubskaya E, Gerber DE, Gettinger SN, Rudin CM, Rizvi N, Crinò L, Blumenschein GR Jr, Antonia SJ, Dorange C, Harbison CT, Graf Finckenstein F, Brahmer JR. Nivolumab versus Docetaxel in Advanced Nonsquamous Non-Small-Cell Lung Cancer. N Engl J Med 2015; doi: 10.1056/NEJMoa1507643
High-dose influenza vaccination is cost-effective in the elderly
High-dose formulation of the trivalent Fluzone influenza vaccine (Sanofi Pasteur) is more cost-effective for older adults than the standard-dose formulation. The analysis, published in The Lancet Infectious Diseases,1 used data from a large 2014 Phase 3/4 trial involving >30,000 subjects aged ≥65 years as well as U.S. healthcare cost data to look for any medical encounters of the participants, including hospitalizations, emergency room visits and use of medicines.
The mean medical costs were lower in subjects vaccinated with high-dose Fluzone compared to recipients of the standard-dose vaccine. These results add to the previous conclusion of the trial that the high-dose formulation is almost 25% more efficacious in older adults.
1. Chit A, Becker DL, DiazGranados CA, Maschio M, Yau E, Drummond M. Cost-effectiveness of high-dose versus standard-dose inactivated influenza vaccine in adults aged 65 years and older: an economic evaluation of data from a randomised controlled trial. Lancet Infect Dis 2015; doi: 10.1016/S1473-3099(15)00249-2
Atezolizumab successful in treating advanced lung cancer
Investigational immunotherapeutic PD-L1 MAb atezolizumab (MPDL3280A, Roche) brought clinical benefits to patients with NSCLC in two Phase‑2 trials. In an open-label study comparing the efficacy of atezolizumab to chemotherapeutic docetaxel in subjects with recurrent locally advanced or metastatic NSCLC, atezolizumab extended survival by 7.7 months.
In a separate single-arm study, atezolizumab was able to shrink tumors in 27% of almost 700 patients, while median survival was not reached.
In both trials, subjects with high levels of PD-L1 expression were pre-selected for treatment. “Results from both of our studies in non-small cell lung cancer showed that measuring PD-L1 may help identify people most likely to respond to atezolizumab, and the majority of responses continued when these data were assessed,” Roche's CMO Sandra Horning said in a statement.
Atezolizumab was granted Breakthrough Therapy Designation from the U.S. FDA earlier in 2015. Like other PD-L1 inhibitors, it prevents the tumor from exploiting one of the pathways that inhibit the immune response.
MMR vaccination coverage decreased in the UK
A year after the peak coverage, the rate of MMR vaccination has decreased in British children, according to an NHS report. In 2014-5, 92.3% of children aged 2 years were vaccinated. The figure was the highest-ever at 92.7% the previous year. Public health officials aim for 95% coverage, which is sufficient to prevent the spread of the infections.
After false allegations of a link between MMR vaccine and autism, the immunization rate dropped to ∼80% in 2004, then started to increase again after 2007. The current overall coverage hides large variations: the rate surpassed 95% in Scotland, Wales and Northern Ireland, but was below 80% in parts of London.
A Phase 2 trial tests a universal influenza vaccine candidate for priming pandemic immunization
A universal influenza vaccine candidate Multimeric-001 (M-001, BiondVax) is entering a Phase 2 trial as a primer for H7N9 immunization. The U.S. NIAID-led study will administer M‑001 several weeks before the pandemic avian influenza vaccine. M‑001 was previously shown to enhance immunogenicity as a primer for the swine flu strain H1N1 in the elderly.
Strain-specific pandemic influenza vaccines take up to 6 months to produce, whereas M‑001 can be produced more rapidly hence stockpiled.
The study will be complemented by an upcoming European trial, in which M‑001 will be tested as a primer for the H5N1 avian influenza vaccine.
ACIP changes recommendation on pneumococcal vaccination in older adults
The U.S. Advisory Committee on Immunization Practices has revised its guidelines for pneumococcal vaccination in immunocompetent adults aged ≥65 years. Specifically, the interval between receiving a dose of PCV13 and of PPSV23 has been set to one year, compared to the previously recommended 6-12 months. This change reflects guidelines for the other sequence of immunization, in which PPSV23 is administered prior to PCV13.
The revised recommendations are based on 16 immunogenicity and safety studies, which indicated that shorter intervals might lead to greater local reactogenicity, while longer intervals might induce stronger immune response. Guidelines for pneumococcal vaccination remain unchanged for other age groups.
Aspirin might improve cancer-immunotherapy outcomes, a preclinical study suggests
Cyclooxigenase (COX) inhibitors, such as aspirin, successfully adjuvanted PD-L1 immunotherapy in mouse models, according to a study published in Cell.1 Certain cancers produce large amounts of prostaglandin E2 (PGE2), which is required for immune suppression and tumor-promoting inflammation. This production is hampered by COX inhibitors.
In the study, genetic ablation of COX or PGE synthases rendered mouse cell line-based models of skin, breast and colorectal cancers susceptible to immune control. Moreover, COX inhibition was able to improve the outcome of anti-PD-L1 treatment in mice, suggesting its potential as an adjuvant for immunotherapy.
“Giving patients COX inhibitors like aspirin at the same time as immunotherapy could potentially make a huge difference to the benefit they get from treatment,” senior author Caetano Reis e Sousa of the Francis Crick Institute said in a statement. “It's still early work, but this could help make cancer immunotherapy even more effective, delivering life-changing results for patients.”
1. Zelenay S, van der Veen AG, Böttcher JP, Snelgrove KJ, Rogers N, Acton SE, Chakravarty P, Girotti MR, Marais R, Quezada SA, Sahai E, Reis E Sousa C. Cyclooxygenase-Dependent Tumor Growth through Evasion of Immunity. Cell 2015; 162:1257-70
IDRI advances its tuberculosis vaccine candidate to Phase 2
The Infectious Disease Research Institute (IDRI) is bringing its tuberculosis (TB) vaccine to a Phase 2a clinical trial to be held in South Africa. The candidate potentially can be used both as a prophylactic and therapeutic vaccine. It has been shown in Phase 1 studies to elicit immune responses in both naïve and BCG-vaccinated healthy adults.
TB can return after successful treatment, and individuals have no symptoms while the disease is dormant, which makes it difficult to contain TB spread. “The Phase IIa trial will be the first dose-escalating TB vaccine trial conducted in persons who have previously had active TB and been successfully treated with a full course of antibiotic therapy,” Rhea Coler of IDRI told the media. “This is an important study population as the incidence of TB can be higher in people recently cured of the disease.”
TB is one of the most serious infectious threats in the developing world. Although the number of cases is declining, according to WHO, there is a growing problem of the emergence of difficult-to-treat multidrug-resistant TB.
Group A Streptococcus vaccine candidate enters clinical trials
StreptAnova (Vaxent) vaccine against Group A Streptococci (GAS) is starting a Phase 1 trial in Halifax, Canada. 45 healthy adults will receive 3 doses in the course of 6 months, and immunogenicity will be assessed one year later.
“The safety and immunogenicity results from these studies will add to the growing body of clinical data from previous human studies of similar vaccines developed in our laboratories. With positive results, clinical development will move to examine the safety and immune response in adolescents and pre-school children, the ultimate target age for the vaccine,” James Dale of University of Tennessee said in a press release.
With >600 million cases each year, GAS is usually associated with mild symptoms, but it can lead to toxic shock syndrome, necrotizing fasciitis and death. There is no available vaccine against GAS.
Shingles vaccine Zostavax is not cost effective for adults 50-60 years old
Zostavax (Merck) protects 2.5% of adults vaccinated in their 50s from shingles, which is not cost-effective, according to a study published in Annals of Internal Medicine.1 Additionally, one case of persistent disease-associated pain is prevented for every 1,000 immunized people.
The U.S. Advisory Committee on Immunization Practices currently does not recommend Zostavax for adults aged 50-60 years, and this might remain the policy despite FDA approval and the fact that the vaccine has shown a 70% efficacy in this age cohort.
Zostavax-induced protection is more persistent in older age, says the senior author Michael Rothberg of Cleveland Clinic. “If you get vaccinated when you’re 50, you’re pretty much unprotected by 60.”
1. Le P, Rothberg MB. Cost-Effectiveness of Herpes Zoster Vaccine for Persons Aged 50 Years. Ann Intern Med 2015; doi: 10.7326/M15-0093