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The HPV-16/18 AS04-adjuvanted vaccine (Cervarix®, GlaxoSmithKline Biologicals) has been shown to induce a robust immune response in women aged 15–55 years (103514/NCT00196937). This follow-up study is the first report of persistence of immune response and safety profile through 48 months after vaccination in women aged 15–55 years. In this open-label, age-stratified Phase III study in Germany and Poland (105882/NCT00196937), healthy women aged 15–55 years received 3 doses of HPV-16/18 AS04-adjuvanted vaccine at 0, 1 and 6 months. Anti-HPV-16/18 seropositivity rates and geometric mean antibody titers (GMTs) were assessed by enzyme-linked immunosorbent assay (ELISA) in women aged 15–25 (n = 168), 26–45 (n = 186) and 46–55 years (n = 177) from the time of first vaccination through 48 months. At Month 48, all subjects were seropositive for anti-HPV-16 antibodies and 99.4% were seropositive for anti-HPV-18. Antibody kinetics were as previously reported, with peak response at Month 7 followed by a gradual decline tending towards a plateau in all age groups. Anti-HPV-16/18 GMTs were sustained at Month 48 in all age groups, including women aged 46–55 years in whom GMTs were respectively 11-fold and 5-fold higher than natural infection levels. The vaccine exhibited a clinically acceptable safety profile in all age groups. In summary, the HPV-16/18 AS04-adjuvanted vaccine induces high and sustained immune responses in women aged 15–55 years, with antibody levels remaining several-fold higher than natural infection levels for at least 4 years after the first vaccine dose.

Nashat Gabrail,1 Ronald Yanagihara,2 Marek Spaczyński,3 William Cooper,4 Erin O'Boyle,5 Carrie Smith,1 Ralph Boccia6 1Gabrail Cancer Center, Canton, OH, USA; 2St Louise Regional Hospital, Gilroy, CA, USA; 3Department of Gynecology, Obstetrics and Gynecologic Oncology, University of Medical Sciences, Poznan, Poland; 4TFS International, Flemington, NJ, USA; 5FibroGen, Inc., San Francisco, CA, USA; 6Center for Cancer and Blood Disorders, Bethesda, MD, USA Background: Despite advances with new therapies, a significant proportion of patients (>30%) suffer delayed-onset chemotherapy-induced nausea and vomiting (CINV) despite use of antiemetics. APF530 is a sustained-release subcutaneous (SC) formulation of granisetron for preventing CINV. APF530 pharmacokinetics, safety, and efficacy were studied in two open-label, single-dose Phase II trials (C2005-01 and C2007-01, respectively) in patients receiving moderately emetogenic chemotherapy or highly emetogenic chemotherapy. Methods: In C2005-01, 45 patients received APF530 250, 500, or 750 mg SC (granisetron 5, 10, or 15 mg, respectively). In C2007-01, 35 patients were randomized to APF530 250 or 500 mg SC. Injections were given 30 to 60 minutes before single-day moderately emetogenic chemotherapy or highly emetogenic chemotherapy. Plasma granisetron was measured from predose to 168 hours after study drug administration. Safety and efficacy were also evaluated. Results: APF530 pharmacokinetics were dose proportional, with slow absorption and elimination of granisetron after a single SC dose. Median time to maximum plasma concentration and half-life were similar for APF530 250 and 500 mg in both trials, with no differences between the groups receiving moderately and highly emetogenic chemotherapy. Exposure to granisetron was maintained at a therapeutic level over the delayed-onset phase, at least 168 hours. Adverse events in both trials were as expected for granisetron; injection site reactions (eg, erythema and induration) were predominantly mild and seen in ≤20% of patients. Complete responses (no emesis, with no rescue medication) were obtained in the acute, delayed, and overall phases in ≥80% and ≥75% of patients in both trials with the 250 and 500 mg doses, respectively. Conclusion: After a single injection of APF530, there were dose-proportional pharmacokinetics and sustained concentrations of granisetron over 168 hours. The 250 and 500 mg doses were well tolerated and maintained therapeutic granisetron levels for ≥5 days. Keywords: cancer, chemotherapy-induced nausea and vomiting, subcutaneous