An AS04-containing human papillomavirus (HPV) 16/18 vaccine for prevention of cervical cancer is immunogenic and well-tolerated in women 15–55 years old

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 1008-1008 ◽  
Author(s):  
T. F. Schwarz
Keyword(s):  
Sexual Debut ◽  
Geometric Mean ◽  
Phase Iii ◽  
Cervical Lesions ◽  
Hpv 16 ◽  
Long Term Follow Up ◽  
Antibody Titers ◽  
Antibody Levels

1008 Background: Genital HPV infections can be acquired shortly after sexual debut, and the risk remains throughout a sexually active woman’s lifetime. In women 15–25 years of age, the AS04-containing HPV vaccine was highly immunogenic and conferred 100% protection against HPV-16/18 persistent infection and associated cervical lesions up to 27 months. In the long-term follow-up of this study, sustained vaccine efficacy has been observed up to 48 months. The present phase III study (580299/014) assessed immune responses to the AS04-containing HPV-16/18 vaccine in women 26–55 years old compared with women 15–25 years old. Methods: Healthy women in Germany and Poland between 15 and 55 years of age received 3 doses of HPV-16/18 AS04-containing vaccine at months 0, 1, and 6. The groups were age stratified: 15–25 (n=229), 26–45 (n=226), and 46–55 (n=211). Anti-HPV-16/18 antibody titers were assessed at months 0, 2, 7, and 12 by ELISA (EU/mL). Seropositivity rates and geometric mean antibody titers (GMTs) were calculated for all groups. Safety was assessed after each dose in all participants. Results: All initially seronegative women became seropositive for both HPV 16 and 18 at Month 2. At Month 7, HPV-16 GMTs (95% CI) were 7908.4 (6874.0–9098.5) in 15–25 year olds, 4029.2 (3402.7–4771.0) in 26–45 year olds, and 2566.8 (2181.2–3020.6) in 46–55 year olds. For HPV-18, GMTs were 3499.3 (3098.7–3951.6) in 15–25 year olds, 1837.3 (1602.1–2107.0) in 26–45 year olds, and 1313.0 (1145.6–1504.9) in 46–55 year olds. Overall the vaccine was well-tolerated, and the incidence of local symptoms (within 30 days) tended to be lower in the 46–55 year-old group (69.2% versus 81.6% [26–45] and 85.7% [15–25]). Conclusions: An AS04-containing HPV-16/18 vaccine was immunogenic and generally safe in 15–55 year-old females. As observed with other vaccines, GMTs decreased with age, however, the Month 7 postvaccination antibody levels in the oldest age group (46–55) were still 3–4 times higher than those observed during a separate long-term follow-up study where sustained efficacy has been observed up to 48 months. [Table: see text]

scholarly journals Efficacy of the bivalent HPV vaccine against HPV 16/18-associated precancer: long-term follow-up results from the Costa Rica Vaccine Trial

2020 ◽  
Vol 21 (12) ◽  
pp. 1643-1652
Author(s):  
Carolina Porras ◽  
Sabrina H Tsang ◽  
Rolando Herrero ◽  
Diego Guillén ◽  
Teresa M Darragh ◽  
...  
Keyword(s):  
Costa Rica ◽  
Hpv Vaccine ◽  
Vaccine Trial ◽  
Hpv 16 ◽  
Long Term Follow Up

Long-term follow-up of a phase III intergroup study of cisplatin alone or in combination with methotrexate, vinblastine, and doxorubicin in patients with metastatic urothelial carcinoma: a cooperative group study.

1997 ◽  
Vol 15 (7) ◽  
pp. 2564-2569 ◽  
Author(s):  
S B Saxman ◽  
K J Propert ◽  
L H Einhorn ◽  
E D Crawford ◽  
I Tannock ◽  
...  
Keyword(s):  
Urothelial Carcinoma ◽  
Combination Chemotherapy ◽  
Performance Status ◽  
Single Agent ◽  
Phase Iii ◽  
Long Term Follow Up ◽  
Intergroup Trial ◽  
Advanced Urothelial Carcinoma

PURPOSE A previously reported randomized intergroup trial demonstrated that combination chemotherapy with methotrexate, vinblastine, doxorubicin, and cisplatin (M-VAC) was superior to single-agent cisplatin in patients with advanced urothelial carcinoma. We conducted a long-term analysis of patients included in the intergroup trial to examine factors associated with long-term survival. PATIENTS AND METHODS Two-hundred fifty-five assessable patients with urothelial carcinoma were randomized to receive either single-agent cisplatin (70 mg/m2 on day 1) or combination chemotherapy with methotrexate (30 mg/m2 on days 1, 15, and 22), vinblastine (3 mg/m2 on days 2, 15, and 22), doxorubicin (30 mg/m2 on day 2), and cisplatin (70 mg/m2 on day 2). Courses were repeated every 28 days. The association between patient characteristics and survival was assessed using Cox proportional hazards models. RESULTS With long-term follow-up evaluation, survival in the M-VAC arm continues to be superior to cisplatin (P = .00015, log-rank test). Predictors of survival include performance status, histology, and the presence of liver or bone metastasis. Only 3.7% of the patients randomized to M-VAC are alive and continuously disease-free at 6 years. CONCLUSION Long-term follow-up evaluation of the intergroup trial confirms that M-VAC is superior to single-agent cisplatin in patients with advanced urothelial carcinoma; however, durable progression-free survival is rare. Patients with non-transitional-cell histology, poor performance status, and/or bone or visceral involvement fare poorly and are unlikely to benefit significantly from M-VAC chemotherapy.

scholarly journals Evaluation of Durability of a Single Dose of the Bivalent HPV Vaccine: The CVT Trial

2020 ◽  
Vol 112 (10) ◽  
pp. 1038-1046 ◽  
Author(s):  
Aimée R Kreimer ◽  
Joshua N Sampson ◽  
Carolina Porras ◽  
John T Schiller ◽  
Troy Kemp ◽  
...  
Keyword(s):  
Single Dose ◽  
Hpv Vaccine ◽  
Hpv Vaccination ◽  
Vaccine Trial ◽  
Enzyme Linked Immunosorbent Assay ◽  
Virus Like Particle ◽  
Long Term Follow Up ◽  
Antibody Levels

Abstract Background The authors investigated the durability of vaccine efficacy (VE) against human papillomavirus (HPV)16 or 18 infections and antibody response among nonrandomly assigned women who received a single dose of the bivalent HPV vaccine compared with women who received multiple doses and unvaccinated women. Methods HPV infections were compared between HPV16 or 18-vaccinated women aged 18 to 25 years who received one (N = 112), two (N = 62), or three (N = 1365) doses, and age- and geography-matched unvaccinated women (N = 1783) in the long-term follow-up of the Costa Rica HPV Vaccine Trial. Cervical HPV infections were measured at two study visits, approximately 9 and 11 years after initial HPV vaccination, using National Cancer Institute next-generation sequencing TypeSeq1 assay. VE and 95% confidence intervals (CIs) were estimated. HPV16 or 18 antibody levels were measured in all one- and two-dose women, and a subset of three-dose women, using a virus-like particle-based enzyme-linked immunosorbent assay (n = 448). Results Median follow-up for the HPV-vaccinated group was 11.3 years (interquartile range = 10.9–11.7 years) and did not vary by dose group. VE against prevalent HPV16 or 18 infection was 80.2% (95% CI = 70.7% to 87.0%) among three-dose, 83.8% (95% CI = 19.5% to 99.2%) among two-dose, and 82.1% (95% CI = 40.2% to 97.0%) among single-dose women. HPV16 or 18 antibody levels did not qualitatively decline between years four and 11 regardless of the number of doses given, although one-dose titers continue to be statistically significantly lower compared with two- and three-dose titers. Conclusion More than a decade after HPV vaccination, single-dose VE against HPV16 or 18 infection remained high and HPV16 or 18 antibodies remained stable. A single dose of bivalent HPV vaccine may induce sufficiently durable protection that obviates the need for more doses.

T1 Top Line Results of the DETECT Enzymatic Debridement Multicenter Randomized Controlled Trial

2020 ◽  
Vol 41 (Supplement_1) ◽  
pp. S1-S1
Author(s):  
William L Hickerson ◽  
Jeremy Goverman ◽  
Sigrid A Blome-Eberwein ◽  
Adam Singer ◽  
Lucy Wibbenmeyer
Keyword(s):  
Median Time ◽  
Wound Closure ◽  
The United States ◽  
Acute Stage ◽  
Phase Iii ◽  
Randomized Controlled ◽  
Multicenter Randomized Controlled Trial ◽  
Long Term Follow Up

Abstract Introduction Bromelain Based Debridement (BBD) of deep burns is approved for use in Europe, Argentina, Russia, South Korea, Peru and Israel. In the United States it is an investigational product and currently there are 2 multicenter RCTs (DETECT – adults, CIDS – children). Patient enrollment in the DETECT adult trial has been completed. The aim of this abstract is to present the acute stage top line results of the DETECT trial. Methods 175 adult patients suffering from deep burns were included in a phase III multicenter, multinational, randomized, controlled, assessor blinded trial. Patients were randomized to 3 arms – BBD, Standard of Care (SOC), or Gel vehicle (Placebo control) in a 3:3:1 ratio (75 BBD, 75 SOC, 25 Gel). The primary endpoint was the incidence of complete eschar removal (BBD vs Gel). Additional acute stage endpoints included the time to complete eschar removal, incidence of surgical eschar removal and eschar removal associated blood loss.Time to complete wound closure (BBD vs SOC) was assessed as a safety endpoint. Following the acute stage, a long-term follow up period of 2 years is being conducted. Results Patient demographics and wound baseline characteristics were comparable across study arms.The incidence of complete eschar removal was significantly higher for BBD vs Gel patients (93.3% vs 4%, p< 0.0001). The incidence of surgical eschar removal was significantly lower for BBD vs SOC patients (4% vs 72%, p< 0.0001). The median time to complete eschar removal was significantly shorter for BBD vs SOC patients (1 day vs 3.8 days, p< 0.0001). Calculated eschar removal associated blood loss was significantly lower for BBD vs SOC patients (14ml vs 815ml, p< 0.0001). The median time to complete wound closure was similar for BBD and SOC patients (27 and 28 days). The overall safety profile of BBD treated patients was good and consistent with the safety data known from previous studies.The results of the long term follow up period are not yet available. Conclusions The acute stage results of this robust phase III RCT demonstrate the safety and efficacy of BBD and are in line with previous trial results. Applicability of Research to Practice The results of this trial may help pave the way for US approval of BBD.

scholarly journals Continued Excellent Outcomes in Previously Untreated Patients With Follicular Lymphoma After Treatment With CHOP Plus Rituximab or CHOP Plus 131I-Tositumomab: Long-Term Follow-Up of Phase III Randomized Study SWOG-S0016

2018 ◽  
Vol 36 (7) ◽  
pp. 697-703 ◽  
Author(s):  
Mazyar Shadman ◽  
Hongli Li ◽  
Lisa Rimsza ◽  
John P. Leonard ◽  
Mark S. Kaminski ◽  
...  
Keyword(s):  
Overall Survival ◽  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Randomized Study ◽  
Phase Iii ◽  
Second Malignancies ◽  
Long Term Follow Up ◽  
Acute Myeloid

Purpose SWOG S0016 was a phase III randomized study that compared the safety and efficacy of R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone) with CHOP-RIT (CHOP followed by consolidation with iodine-133–tositumomab radioimmunotherapy) for previously untreated patients with follicular lymphoma. Understanding the long-term outcome of patients provides a benchmark for novel treatment regimens for FL. Patients and Methods Between 2001 and 2008, 531 previously untreated patients with FL were randomly assigned to receive either six cycles of R-CHOP or six cycles of CHOP-RIT. Patients with advanced-stage disease (bulky stage II, III, or IV) of any pathologic grade (1, 2, or 3) were eligible. Results After a median follow-up of 10.3 years, 10-year estimates of progression-free and overall survival were 49% and 78% among all patients, respectively. Patients in the CHOP-RIT arm had significantly better 10-year progression-free survival compared with patients in the R-CHOP arm (56% v 42%; P = .01), but 10-year overall survival was not different between the two arms (75% v 81%; P = .13). There was no significant difference between the CHOP-RIT and R-CHOP arms in regard to incidence of second malignancies (15.1% v 16.1%; P = .81) or myelodysplastic syndrome or acute myeloid leukemia (4.9% v 1.8%; P = .058). The estimated 10-year cumulative incidences of death resulting from second malignancies were not different (7.1% v 3.2%; P = .16), but cumulative incidence of death resulting from myelodysplastic syndrome or acute myeloid leukemia was higher in the CHOP-RIT arm compared with the R-CHOP arm (4% v 0.9%; P = .02). Conclusion Given these outstanding outcomes, immunochemotherapy should remain the standard induction approach for patients with high-risk FL until long-term follow-up of alternative approaches demonstrates superiority.

scholarly journals LTBK-12. EORTC 26951, RANDOMIZED STUDY OF ADJUVANT PCV AFTER 59.4 GY RADIOTHERAPY: VERY LONG TERM FOLLOW-UP

2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi285-vi285
Author(s):  
Martin van den Bent ◽  
Khe Hoang-Xuan ◽  
Alba Brandes ◽  
Johan Kros ◽  
M C M Kouwenhoven ◽  
...  
Keyword(s):  
Randomized Study ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Term Survival ◽  
Long Term Survival ◽  
Kaplan Meier ◽  
Tumor Group ◽  
Long Term Follow Up

Abstract BACKGROUND Between 1995 and 2002 the EORTC Brain Tumor Group conducted a prospective phase III study on adjuvant procarbazine, CCNU and vincristine (PCV) chemotherapy in anaplastic oligodendroglioma (AOD). A mature follow-up presented in 2012 showed survival benefit of the addition of PCV, in particular in 1p/19q co-deleted tumors and tumors with MGMT promoter methylation. We now present very long term follow-up. MATERIALS AND METHODS Patients were eligible if locally diagnosed with a newly diagnosed AOD. They were randomized between radiotherapy (RT, 33 x 1.8 Gy) and the same RT followed by 6 cycles PCV (RT/PCV). Primary endpoints were overall survival (OS) and progression free survival (PFS). 1p/19q status (FISH) was determined in 300 patient. Kaplan- Meier technique and Cox modeling were used for long term survival analysis. Primary analyses were adjusted for known prognostic factors. For other analyses no adjustment was performed. RESULTS With 368 patients included, a median follow-up of 18.4 years and 307 (83%) survival events, median and 20-year survival after RT/PCV versus RT alone were 42.3 mo and 16.8% vs 30.6 months and 10.1% (HR 0.78; 95% CI (0.63, 0.98), adjusted p=0.06). Eighty patients were 1p/19q codel of which 26 (33%) were still alive, in this subgroup median and 20-year survival after RT/PCV versus RT alone were 14 years and 37.1% versus 9.3 years and 13.6% (HR 0.60, 95% CI (0.35, 1.03), unadjusted p=0.06). Twenty year PFS in 1p/19q codel was 31.3% in RT/PCV treated patients and 10.8% in RT only treated patients (HR 0.49, 95% CI (0.29, 0.83), unadjusted p=0.007). In the 1p/19q codel subgroup age, WHO PS and necrosis at pathology were identified to be of independent prognostic value for OS. CONCLUSION This long term analysis confirms the earlier conclusions and provides data on long term survival in this patient group. In 1p/19q codel patients treated with RT/PCV, the 20-year PFS and OS rates are 31% and 37% respectively.

Long-term follow-up of autotransplant (AT)-supported high-dose melphalan (hdm) for multiple myeloma (MM): Update of Intergroup Francophone du Myelome (IFM), Southwest Oncology Group (SWOG), and Arkansas (ARK) Total Therapy (TT) trials

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 8519-8519
Author(s):  
B. Barlogie ◽  
M. Attal ◽  
J. Crowley ◽  
J. Harousseau
Keyword(s):  
Phase Iii ◽  
Long Term Results ◽  
High Dose ◽  
Long Term Follow Up ◽  
Phase Iii Trials ◽  
Trial Outcomes ◽  
Total Therapy ◽  
High Dose Melphalan

8519 Background: Clinical trial outcomes are usually published when statistical protocol objectives have been met, with short median follow-up not exceeding 5 years. Due to treatment innovations, MM survival beyond 10 years has become more common but formal long-term results are seldom reported. Methods: IFM, SWOG and ARK provide an update of their major trials. IFM-90: 1 AT v standard therapy (STD), IFM-94: 2 v 1 AT, IFM-9902: 2AT ± THAL, IFM-9904: 2AT for high-risk MM; SWOG-9321: 1 AT v STD; TT1: 2 AT with interferon, TT2: 2AT ± THAL, TT3: 2AT + THAL + bortezomib. Results: OS clustered in 3 groups with superior outcomes for TT3/TT2/IFM-99 v TT1 v IFM-94/ IFM-90/SWOG-9321 with 5/10/15-yr estimates of 70%/50%/TE v 57%/35%/20% v 43%/25%/15% (p<0.0001). EFS also clustered in 3 groups with superior outcomes for TT3 v TT2 v remainder with estimates of 71%/TE/TE v 50%/35%/TE v 27%/ 15%/10% (p<0.0001). Among phase III trials, added THAL in TT2 increased 10-yr OS/EFS from 40%/25% to 60%/40% (p=0.04/p=0.0005); 10-yr OS was 30% v 8% with 1 v 0 AT in IFM-90 (p=0.005), 31% v 21% with 2 AT v 1 AT in IFM-94 (p=0.08), and 20% for both arms of S9321. On multivariate analysis involving 2962 patients, OS was adversely affected by B2M >=3.5mg/L (p<0.001), LDH >=ULN (p<0.001), hemoglobin <10g/dL (p=0.001) and albumin <3.5g/dL (p=0.02). 2AT (65%) and THAL (21%) both contributed independently to superior OS (p<0.001, p=0.002); among individual trials, IFM-9902 (19%) and TT2/TT3 (33%) both improved OS significantly (both p<0.001). For each of the 3 major OS clusters, 228 patients could be matched on B2M, LDH, hemoglobin and albumin, with 10-yr OS/EFS estimates of 65%/30% for the TT3/TT2/IFM-9902 group significantly exceeding 30%/15% each for the other 2 groups (p=0.001/p=0.001). Conclusions: A 15-yr EFS plateau of 10% with older trials and superior 10-yr EFS/OS estimates of 50%/35% with recent studies emphasize that cure should be a realistic trial objective in contemporary MM therapy, requiring however very long-term follow-up beyond 15 years. [Table: see text]

scholarly journals Evaluation of the Long-Term Anti-Human Papillomavirus 6 (HPV6), 11, 16, and 18 Immune Responses Generated by the Quadrivalent HPV Vaccine

2015 ◽  
Vol 22 (8) ◽  
pp. 943-948 ◽  
Author(s):  
Mari Nygård ◽  
Alfred Saah ◽  
Christian Munk ◽  
Laufey Tryggvadottir ◽  
Espen Enerly ◽  
...  
Keyword(s):  
Human Papillomavirus ◽  
Geometric Mean ◽  
Strongly Correlated ◽  
Serum Samples ◽  
Base Study ◽  
Long Term Follow Up ◽  
Hpv Types ◽  
Current Report

ABSTRACTThis quadrivalent human papillomavirus (qHPV) (HPV6, -11, -16, and -18) vaccine long-term follow-up (LTFU) study is an ongoing extension of a pivotal clinical study (FUTURE II) taking place in the Nordic region. The LTFU study was designed to evaluate the effectiveness, immunogenicity, and safety of the qHPV vaccine (Gardasil) for at least 10 years following completion of the base study. The current report presents immunogenicity data from testing samples of the year 5 LTFU visit (approximately 9 years after vaccination). FUTURE II vaccination arm subjects, who consented to being followed in the LTFU, donated serum at regular intervals and in 2012. Anti-HPV6, -11, -16, and -18 antibodies were detected by the competitive Luminex immunoassay (cLIA), and in addition, serum samples from 2012 were analyzed by the total IgG Luminex immunoassay (LIA) (n= 1,598). cLIA geometric mean titers (GMTs) remained between 70% and 93% of their month 48 value depending on HPV type. For all HPV types, the lower bound of the 95% confidence interval (CI) for the year 9 GMTs remained above the serostatus cutoff value. The proportion of subjects who remained seropositive based on the IgG LIA was higher than the proportion based on cLIA, especially for anti-HPV18. As expected, the anti-HPV serum IgG and cLIA responses were strongly correlated for all HPV types. Anti-HPV GMTs and the proportion of vaccinated individuals who are seropositive remain high for up to 9 years of follow-up after vaccination.

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