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Late-breaking abstracts presented for the Thirty-Ninth Annual Meeting of the Society of Gynecologic Oncologists
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Gynecologic Oncology 109 (2008) 158 – 159 www.elsevier.com/locate/ygyno
Abstracts Late-breaking abstracts presented for the Thirty-Ninth Annual Meeting of the Society of Gynecologic Oncologists 1 Sustained immunogenicity and high efficacy against HPV16/18 related cervical neoplasia: Long-term follow up through 6.4 years in women vaccinated with Cervarix™ (GSK's HPV 16/18 AS04 candidate vaccine) D. Harper1, S. Gall2, P. Naud3, W. Quint4, G. Dubin5, D. Jenkins6, A. Schuind.5 1Dartmouth Medical School, Lebanon, NH, 2University of Louisville, Louisville, KY, 3Federal University of RS-UFRGS/HCPA, Porto Alegre, Brazil, 4 DDL Diagnostics Laboratory, Voorburg, The Netherlands, 5 GlaxoSmithKline, King of Prussia, PA, 6GlaxoSmithKline Biologicals, Rixensart, Belgium. Objectives: Long-lasting protection against oncogenic HPV infection and associated cervical neoplasia is a key consideration in the prevention of cervical cancer with prophylactic vaccination. We have previously shown in an extended follow-up (EFU) phase [580299/007] of an initial efficacy study [580299/001] that Cervarix™ is highly immunogenic and sustains protection up to 5.5 years against HPV 16/18 infections and related cytohistological outcomes, and crossprotection against incident infections with oncogenic HPV types 31 and 45, which are not included in the vaccine [Gall AACR 2007]. Our objective was to evaluate in the final analysis of the EFU, long-term immunogenicity, vaccine efficacy and safety. Methods: In the initial efficacy study, 1113 women 15– 25 years old in North America and Brazil received 3 doses of HPV 16/18 ASO4 vaccine or Al(OH)3 at months 0, 1 and 6. The EFU phase enrolled 776 participants who were HPV 16- and 18-seronegative and DNA-negative for 14 high-risk HPV types at entry into the initial study. HPV 16/18 antibody titers were assessed. Cervical samples were collected at 6-month intervals and DNA was detected using PCR. Results: During the EFU phase, ≥ 98% of women evaluated remained seropositive for both HPV 16 and 18 with sustained HPV 16 and 18 antibody levels several fold higher than natural infection levels for both total IgG and neutralizing antibodies. Substantial vaccine efficacy (VE, 95% CI) was observed against HPV 16 and/or 18 endpoints: incident infection (97%, 87–100), 6-month persistent infection (100%, 86–100) and 12-month persistent infection (100%, 75–100). Over a total of 6.4 years of follow-up (combined initial efficacy and EFU), VE was 100% (73–100) against HPV 16/18 associated CIN1+ (0 vs. 15 cases) 0090-8258/$ - see front matter © 2008 Published by Elsevier Inc. doi:10.1016/j.ygyno.2008.02.017
and 100% (51–100) against CIN2+ (0 vs. 9 cases). VE was 72% (21–92) against CIN2+ lesions independent of HPV status (5 vs. 17 cases). Furthermore, substantial cross protection against incident infection with non-vaccine oncogenic types HPV 45 and 31 was maintained. Safety data were comparable in both vaccine and placebo groups. Conclusions: Our findings provide evidence that Cervarix™ is highly efficacious against HPV 16/18-related cervical lesions as well as CIN2+ lesions regardless of associated HPV type and induced antibody levels that remain high for HPV 16 and 18 up to 6.4 years. Observed additional protection against other oncogenic types may provide further benefit to the reduction of HPV-related cervical disease. 2 Baseline vaccine type seropositivity and DNA positivity of women aged 24–45 participating in a phase III clinical trial of quadrivalent HPV (type 6/11/16/18) L1 VLP vaccine S. Makhija 1 , FUTURE III Investigators. 1 University of Alabama at Birmingham, Birmingham, AL. Objectives: Prophylactic administration of quadrivalent HPV (types 6/11/16/18) L1 virus-like-particle (VLP) vaccine is highly effective in preventing HPV 6/11/16/18-related cervical and genital disease in adolescent and young adult women naïve to vaccine HPV types. In the combined international clinical program for the quadrivalent vaccine, 73% of young women aged 16–26 were naïve via serology and PCR to all 4 vaccine HPV types. Although the incidence of HPV disease peaks within 10 years of sexual debut, women remain susceptible to HPV infection and its related diseases throughout their lives. We sought to evaluate the baseline level of HPV exposure among women aged 24–45 enrolled in a phase III clinical trial of quadrivalent HPV vaccine. Methods: An international, placebo-controlled study of quadrivalent HPV vaccine was conducted. This study enrolled 3819 24- to 45-year-old women with no history of cervical disease in the past 5 years, LEEP, hysterectomy, or genital warts. Subjects underwent genital inspection, Pap testing, and collection of cervical, vulvar, perineal and perianal specimens for HPV PCR at enrollment. Serology data were also gathered at enrollment for detection of HPV antibody titers via competitive Luminex immunoassay (cLIA). Results: Among women aged 24–45, 67% of subjects were naïve to HPV 6/11/16/18 at enrollment by both serology and PCR testing. 23% of subjects had evidence of current or past infection at enrollment with exactly 1 vaccine HPV type; 0.4%
ABSTRACTS / Gynecologic Oncology 109 (2008) 158–159
had evidence of current or past infection with all 4 vaccine HPV types. Eight percent of subjects were positive for HPV 6, 11, 16 or 18 DNA at enrollment; 30% were positive by serology. Among women infected with HPV 6, 11, 16, or 18 DNA at enrollment, only 0.7% was infected with more than 1 vaccine HPV type. Conclusions: Women aged 24–45 remain at risk for HPV infection and disease. A large proportion of these women remains naïve to all 4 vaccine HPV types. Therefore, the majority of these women would likely benefit from prophylactic vaccination with quadrivalent HPV vaccine. 3 A novel multiple marker bioassay utilizing HE4 and CA125II for the prediction of ovarian cancer in patients with a pelvic mass R. Moore1, S. McMeeken2, A. Brown3, P. DiSilvestro1, C. Miller4, J. Allard4, W. Gajewski5, R. Kurman6, R. Bast Jr.7, S. Skates8. 1Women and Infants' Hospital, Brown University, Providence, RI, 2Oklahoma University, Oklahoma City, OK, 3 Hartford Hospital, Hartford, CT, 4Fujirebio Diagnostics Inc., Malvern, PA, 5 New Hanover Regional Medical Center, Wilmington, NC, 6Johns Hopkins Medical School, Baltimore, MD, 7 University of Texas MD Anderson Cancer Center, Houston, TX, 8Harvard Medical School, Massachusetts General Hospital, Boston, MA. Objectives: Patients who are diagnosed with epithelial ovarian cancer (EOC) have decreased morbidity and increased survival when cared for by surgeons and at centers experienced in the management of EOC. It is critical that these patients be referred to appropriate centers prior to their surgery. The objective of this trial was to validate a predictive model to assess the risk for EOC in women with a pelvic mass and the use of the model as a tool to triage patients to specialized centers prior to surgery.
159
Methods: This was an IRB-approved multicenter doubleblinded prospective trial. All women enrolled gave full informed consent, had a pelvic mass and were to have surgical intervention. All blood samples were collected preoperatively and serum levels for HE4 and CA125II were determined. Separate logistic regression algorithms for pre- and postmenopausal women stratified patients into low- and high-risk groups. All pathology was confirmed by a central pathology review with gynecologic pathologists. Results: Twelve sites enrolled 566 women with 523 evaluable patients. There were 127 EOC (17 stage I, 17 stage II, 83 stage III, 6 stage IV, and 4 unstaged), 22 LMP tumors, 6 non-EOC and 21 non-ovarian cancers. Of the EOC, 82 were serous, 15 endometrioid, 6 mucinous, 6 clear cell, 8 mixed, 3 MMMT, 1 adenosquamous, 1 transitional cell, and 5 undifferentiated. In the postmenopausal group there were; 184 benign cases, 8 LMP tumors and 112 EOC. Of the benign cases, 138 (75%) were classified as low risk and 46 (25%) as high risk. Of the EOC and LMP cases, 7 (6%) were classified as low risk (2 LMP tumors, 3 stage II, 1 stage III, and 1 unstaged EOC) and 113 (94%) as high risk, giving a sensitivity of 94.2% (95% CI = 88.4–97.6), a specificity of 75.0% (95% CI = 68.1–88.1) and a NPV of 95.2% (95% CI = 90.3–98.0). In the premenopausal group, there were 163 benign cases, 14 LMP tumors, and 15 EOC. Of the benign cases, 122 (75%) were classified as low risk and 41 (25%) as high risk. Of the EOC and LMP cases, 7 (24%) were classified as low risk (5 LMP tumors, 1 stage I, and 1 unstaged EOC) and 22 (76%) as high risk, giving a sensitivity of 75.9% (95% CI = 56.5–89.7), a specificity of 74.8% (95% CI = 67.5–81.3) and a NPV of 94.6% (95% CI = 89.1–97.8). Conclusions: A multiple marker algorithm utilizing serum levels of HE4 and CA125II permits effective stratification of patients with 95% of all EOC being correctly placed in the highrisk group and 75% of benign cases in the low-risk group. This model can be used to triage patients with a pelvic mass to centers of excellence.
Gynecologic Oncology 109 (2008) 158 – 159 www.elsevier.com/locate/ygyno
Abstracts Late-breaking abstracts presented for the Thirty-Ninth Annual Meeting of the Society of Gynecologic Oncologists 1 Sustained immunogenicity and high efficacy against HPV16/18 related cervical neoplasia: Long-term follow up through 6.4 years in women vaccinated with Cervarix™ (GSK's HPV 16/18 AS04 candidate vaccine) D. Harper1, S. Gall2, P. Naud3, W. Quint4, G. Dubin5, D. Jenkins6, A. Schuind.5 1Dartmouth Medical School, Lebanon, NH, 2University of Louisville, Louisville, KY, 3Federal University of RS-UFRGS/HCPA, Porto Alegre, Brazil, 4 DDL Diagnostics Laboratory, Voorburg, The Netherlands, 5 GlaxoSmithKline, King of Prussia, PA, 6GlaxoSmithKline Biologicals, Rixensart, Belgium. Objectives: Long-lasting protection against oncogenic HPV infection and associated cervical neoplasia is a key consideration in the prevention of cervical cancer with prophylactic vaccination. We have previously shown in an extended follow-up (EFU) phase [580299/007] of an initial efficacy study [580299/001] that Cervarix™ is highly immunogenic and sustains protection up to 5.5 years against HPV 16/18 infections and related cytohistological outcomes, and crossprotection against incident infections with oncogenic HPV types 31 and 45, which are not included in the vaccine [Gall AACR 2007]. Our objective was to evaluate in the final analysis of the EFU, long-term immunogenicity, vaccine efficacy and safety. Methods: In the initial efficacy study, 1113 women 15– 25 years old in North America and Brazil received 3 doses of HPV 16/18 ASO4 vaccine or Al(OH)3 at months 0, 1 and 6. The EFU phase enrolled 776 participants who were HPV 16- and 18-seronegative and DNA-negative for 14 high-risk HPV types at entry into the initial study. HPV 16/18 antibody titers were assessed. Cervical samples were collected at 6-month intervals and DNA was detected using PCR. Results: During the EFU phase, ≥ 98% of women evaluated remained seropositive for both HPV 16 and 18 with sustained HPV 16 and 18 antibody levels several fold higher than natural infection levels for both total IgG and neutralizing antibodies. Substantial vaccine efficacy (VE, 95% CI) was observed against HPV 16 and/or 18 endpoints: incident infection (97%, 87–100), 6-month persistent infection (100%, 86–100) and 12-month persistent infection (100%, 75–100). Over a total of 6.4 years of follow-up (combined initial efficacy and EFU), VE was 100% (73–100) against HPV 16/18 associated CIN1+ (0 vs. 15 cases) 0090-8258/$ - see front matter © 2008 Published by Elsevier Inc. doi:10.1016/j.ygyno.2008.02.017
and 100% (51–100) against CIN2+ (0 vs. 9 cases). VE was 72% (21–92) against CIN2+ lesions independent of HPV status (5 vs. 17 cases). Furthermore, substantial cross protection against incident infection with non-vaccine oncogenic types HPV 45 and 31 was maintained. Safety data were comparable in both vaccine and placebo groups. Conclusions: Our findings provide evidence that Cervarix™ is highly efficacious against HPV 16/18-related cervical lesions as well as CIN2+ lesions regardless of associated HPV type and induced antibody levels that remain high for HPV 16 and 18 up to 6.4 years. Observed additional protection against other oncogenic types may provide further benefit to the reduction of HPV-related cervical disease. 2 Baseline vaccine type seropositivity and DNA positivity of women aged 24–45 participating in a phase III clinical trial of quadrivalent HPV (type 6/11/16/18) L1 VLP vaccine S. Makhija 1 , FUTURE III Investigators. 1 University of Alabama at Birmingham, Birmingham, AL. Objectives: Prophylactic administration of quadrivalent HPV (types 6/11/16/18) L1 virus-like-particle (VLP) vaccine is highly effective in preventing HPV 6/11/16/18-related cervical and genital disease in adolescent and young adult women naïve to vaccine HPV types. In the combined international clinical program for the quadrivalent vaccine, 73% of young women aged 16–26 were naïve via serology and PCR to all 4 vaccine HPV types. Although the incidence of HPV disease peaks within 10 years of sexual debut, women remain susceptible to HPV infection and its related diseases throughout their lives. We sought to evaluate the baseline level of HPV exposure among women aged 24–45 enrolled in a phase III clinical trial of quadrivalent HPV vaccine. Methods: An international, placebo-controlled study of quadrivalent HPV vaccine was conducted. This study enrolled 3819 24- to 45-year-old women with no history of cervical disease in the past 5 years, LEEP, hysterectomy, or genital warts. Subjects underwent genital inspection, Pap testing, and collection of cervical, vulvar, perineal and perianal specimens for HPV PCR at enrollment. Serology data were also gathered at enrollment for detection of HPV antibody titers via competitive Luminex immunoassay (cLIA). Results: Among women aged 24–45, 67% of subjects were naïve to HPV 6/11/16/18 at enrollment by both serology and PCR testing. 23% of subjects had evidence of current or past infection at enrollment with exactly 1 vaccine HPV type; 0.4%
ABSTRACTS / Gynecologic Oncology 109 (2008) 158–159
had evidence of current or past infection with all 4 vaccine HPV types. Eight percent of subjects were positive for HPV 6, 11, 16 or 18 DNA at enrollment; 30% were positive by serology. Among women infected with HPV 6, 11, 16, or 18 DNA at enrollment, only 0.7% was infected with more than 1 vaccine HPV type. Conclusions: Women aged 24–45 remain at risk for HPV infection and disease. A large proportion of these women remains naïve to all 4 vaccine HPV types. Therefore, the majority of these women would likely benefit from prophylactic vaccination with quadrivalent HPV vaccine. 3 A novel multiple marker bioassay utilizing HE4 and CA125II for the prediction of ovarian cancer in patients with a pelvic mass R. Moore1, S. McMeeken2, A. Brown3, P. DiSilvestro1, C. Miller4, J. Allard4, W. Gajewski5, R. Kurman6, R. Bast Jr.7, S. Skates8. 1Women and Infants' Hospital, Brown University, Providence, RI, 2Oklahoma University, Oklahoma City, OK, 3 Hartford Hospital, Hartford, CT, 4Fujirebio Diagnostics Inc., Malvern, PA, 5 New Hanover Regional Medical Center, Wilmington, NC, 6Johns Hopkins Medical School, Baltimore, MD, 7 University of Texas MD Anderson Cancer Center, Houston, TX, 8Harvard Medical School, Massachusetts General Hospital, Boston, MA. Objectives: Patients who are diagnosed with epithelial ovarian cancer (EOC) have decreased morbidity and increased survival when cared for by surgeons and at centers experienced in the management of EOC. It is critical that these patients be referred to appropriate centers prior to their surgery. The objective of this trial was to validate a predictive model to assess the risk for EOC in women with a pelvic mass and the use of the model as a tool to triage patients to specialized centers prior to surgery.
159
Methods: This was an IRB-approved multicenter doubleblinded prospective trial. All women enrolled gave full informed consent, had a pelvic mass and were to have surgical intervention. All blood samples were collected preoperatively and serum levels for HE4 and CA125II were determined. Separate logistic regression algorithms for pre- and postmenopausal women stratified patients into low- and high-risk groups. All pathology was confirmed by a central pathology review with gynecologic pathologists. Results: Twelve sites enrolled 566 women with 523 evaluable patients. There were 127 EOC (17 stage I, 17 stage II, 83 stage III, 6 stage IV, and 4 unstaged), 22 LMP tumors, 6 non-EOC and 21 non-ovarian cancers. Of the EOC, 82 were serous, 15 endometrioid, 6 mucinous, 6 clear cell, 8 mixed, 3 MMMT, 1 adenosquamous, 1 transitional cell, and 5 undifferentiated. In the postmenopausal group there were; 184 benign cases, 8 LMP tumors and 112 EOC. Of the benign cases, 138 (75%) were classified as low risk and 46 (25%) as high risk. Of the EOC and LMP cases, 7 (6%) were classified as low risk (2 LMP tumors, 3 stage II, 1 stage III, and 1 unstaged EOC) and 113 (94%) as high risk, giving a sensitivity of 94.2% (95% CI = 88.4–97.6), a specificity of 75.0% (95% CI = 68.1–88.1) and a NPV of 95.2% (95% CI = 90.3–98.0). In the premenopausal group, there were 163 benign cases, 14 LMP tumors, and 15 EOC. Of the benign cases, 122 (75%) were classified as low risk and 41 (25%) as high risk. Of the EOC and LMP cases, 7 (24%) were classified as low risk (5 LMP tumors, 1 stage I, and 1 unstaged EOC) and 22 (76%) as high risk, giving a sensitivity of 75.9% (95% CI = 56.5–89.7), a specificity of 74.8% (95% CI = 67.5–81.3) and a NPV of 94.6% (95% CI = 89.1–97.8). Conclusions: A multiple marker algorithm utilizing serum levels of HE4 and CA125II permits effective stratification of patients with 95% of all EOC being correctly placed in the highrisk group and 75% of benign cases in the low-risk group. This model can be used to triage patients with a pelvic mass to centers of excellence.