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The 2012 Annual Meeting on Women's Cancer
Gynecologic Oncology 126 (2012) 3–4
Contents lists available at SciVerse ScienceDirect
Gynecologic Oncology journal homepage: www.elsevier.com/locate/ygyno
Conference Report The 2012 Annual Meeting on Women's Cancer
Ovarian cancer Investigators from The Cancer Genome Atlas (TCGA) identified elements of a molecular profile for ovarian cancer patients considered cured by standard therapy. Three candidate genes (CYP4B1, CEPT1, CHMP4A) were over-represented in advanced stage women who did not recur within 5 years after primary therapy. A secondary analysis of the optimally cytoreduced patients on GOG 182 concluded that for patients with b1 cm residual tumor, surgical complexity was not associated with improved OS or PFS. However, if high surgical complexity procedures resulted in microscopic residual, these patients had improved outcomes relative to patients with b1 cm residual disease achieved with surgery. The results suggested that tumor biology is an important component of survival despite aggressive surgical efforts. Aggressive surgery cannot completely negate the prognostic implication of extensive disease. A second analysis of GOG 182 found that 18% of optimally cytoreduced patients required upper abdominal procedures, and that 14% of patients with residual disease had diaphragm disease as their only remaining site. Since patients with no residual had improved outcomes, removal of diaphragm disease may afford benefit. Finally, a single institution study of whether patients who undergo complete cytoreduction benefit from lymphadenectomy concluded that although occult metastases were seen in 31%, lymphadenectomy was not associated with improved survival. The Hugh Barber Outstanding Abstract Award entitled “Disparities in epithelial ovarian cancer according to race and socioeconomic status: Adherence to National Comprehensive Cancer Network (NCCN) guidelines and survival outcomes, a study of 47,160 patients from the National Cancer Data Base” was presented by Dr. Robert Bristow. The data highlighted significant disparities in the quality of ovarian cancer care and overall survival along racial and socioeconomic status lines independent of NCCN guidelines. It also underscored the inequalities in healthcare delivery within the current healthcare system in the U.S. Three seminal abstracts with novel findings were presented. The results from a second interim OS analysis from the OCEANS trial revealed that adding bevacizumab did not translate into an overall survival benefit for patients with recurrent platinum sensitive ovarian cancer. A randomized phase II trial of the PARP inhibitor olaparib in patients with platinum-sensitive relapsed serous ovarian cancer revealed that the initial improved median PFS compared with placebo (8.4 vs 4.8 months) did not impart an overall survival benefit. The randomized phase II Precedent Trial of EC145 and pegylated liposomal doxorubicin (PLD) versus PLD alone in subjects with platinumresistant ovarian cancer showed initial benefit. This was the first study to show that EC145 in combination with PLD improved PFS
doi:10.1016/j.ygyno.2012.05.005
and OS over standard therapy in patients with platinum resistant ovarian cancer. Endometrial carcinoma Preliminary results from The Cancer Genome Atlas (TCGA) project showed that both endometrioid and serous uterine cancers had more genomic instability than initially suspected. A cost-effectiveness analysis of selective versus routine lymphadenectomy in presumed early endometrial cancer showed routine removal to be more costeffective. A second analysis concluded that lymphadenectomy could be omitted in low risk patients (preoperative grade 1 or 2, size ≤ 2 cm), even in the setting of unavailable or unreliable frozen section, as no patients in this subgroup had nodal recurrences. New phase II data in advanced or recurrent endometrial cancer included the results from the GOG 229G combination of bevacizumab and temsirolimus. The response rate in this pretreated population was acceptable (25%), but toxicity was moderate including rectovaginal fistula, bowel perforation and three associated deaths. Cervical carcinoma A phase II trial combining the biological agent erolitinib with chemo-radiation for stage IIB-IIIB cervical cancer was superior to historical controls, with 94% complete responses. A phase II trial of neoadjuvant chemotherapy with cisplatin and paclitaxel for locally advanced disease, followed by radical surgery and an additional six chemotherapy cycles showed promising results in both nodenegative and node-positive patients, with five year OS of 78%. Oncofertility Treatment with high-dose MPA for atypical hyperplasia or low grade endometrial cancer allowed 42 pregnancies in 155 women in a retrospective cohort. Post-pregnancy surveillance was essential in patients with cancer not undergoing subsequent hysterectomy, as the relapse rate within 5 years was 73%. In women with serous borderline tumors who received fertility-sparing treatment, a retrospective review showed an increased risk for recurrence (35% versus 15%), but no difference in overall survival. Nodal involvement was not associated with increased recurrence risk. Morbidity issues A prospective evaluation of aggressive control of hyperglycemia with continuous insulin infusion at one institution decreased surgical site infections by 40%. A SEER data review demonstrated that cardiac
4
Conference Report
death is the most significant mortality determinant for endometrial cancer patients, and that management of cardiac risk factors was likely the most crucial post-treatment intervention. Cutting edge science Preliminary results from the GOG 209 randomized phase III non-inferiority trial of first line chemotherapy for metastatic or recurrent endometrial showed that the combination of paclitaxel and carboplatin (TC) was not inferior to the combination of doxorubicin, cisplatin and paclitaxel (TAP). The phase II results of GOG 251 showed bevacizumab to be an active regimen for recurrent sex cord stromal tumors, with partial response in 17% and stable disease in 78%. Drug development in ovarian cancer Clinical outcomes of 122 patients with gynecologic malignancies enrolled on 30 phase I trials at one institution over a 12 year period
dispelled the myths of a high rate of toxicity and low rate of clinical benefits. Phase I outcomes for the novel topoisomerase inhibitor belotecan and oral etoposide in seven patients with platinumresistant ovarian cancer include four objectives and two complete responses. Early activity was also shown for the combination of the PARP inhibitor veliparib and liposomal doxorubicin in recurrent ovarian cancer. Finally, a modified intraperitoneal regimen for primary treatment with day one intravenous paclitaxel and bevacizumab followed by day two intraperitoneal cisplatin appears active, with 42 month PFS and mild cumulative neuropathy as the primary toxicity.
Eric L. Eisenhauer The Ohio State University Medical Center, USA Jean A. Hurteau University of Chicago Pritzker School of Medicine, USA
Contents lists available at SciVerse ScienceDirect
Gynecologic Oncology journal homepage: www.elsevier.com/locate/ygyno
Conference Report The 2012 Annual Meeting on Women's Cancer
Ovarian cancer Investigators from The Cancer Genome Atlas (TCGA) identified elements of a molecular profile for ovarian cancer patients considered cured by standard therapy. Three candidate genes (CYP4B1, CEPT1, CHMP4A) were over-represented in advanced stage women who did not recur within 5 years after primary therapy. A secondary analysis of the optimally cytoreduced patients on GOG 182 concluded that for patients with b1 cm residual tumor, surgical complexity was not associated with improved OS or PFS. However, if high surgical complexity procedures resulted in microscopic residual, these patients had improved outcomes relative to patients with b1 cm residual disease achieved with surgery. The results suggested that tumor biology is an important component of survival despite aggressive surgical efforts. Aggressive surgery cannot completely negate the prognostic implication of extensive disease. A second analysis of GOG 182 found that 18% of optimally cytoreduced patients required upper abdominal procedures, and that 14% of patients with residual disease had diaphragm disease as their only remaining site. Since patients with no residual had improved outcomes, removal of diaphragm disease may afford benefit. Finally, a single institution study of whether patients who undergo complete cytoreduction benefit from lymphadenectomy concluded that although occult metastases were seen in 31%, lymphadenectomy was not associated with improved survival. The Hugh Barber Outstanding Abstract Award entitled “Disparities in epithelial ovarian cancer according to race and socioeconomic status: Adherence to National Comprehensive Cancer Network (NCCN) guidelines and survival outcomes, a study of 47,160 patients from the National Cancer Data Base” was presented by Dr. Robert Bristow. The data highlighted significant disparities in the quality of ovarian cancer care and overall survival along racial and socioeconomic status lines independent of NCCN guidelines. It also underscored the inequalities in healthcare delivery within the current healthcare system in the U.S. Three seminal abstracts with novel findings were presented. The results from a second interim OS analysis from the OCEANS trial revealed that adding bevacizumab did not translate into an overall survival benefit for patients with recurrent platinum sensitive ovarian cancer. A randomized phase II trial of the PARP inhibitor olaparib in patients with platinum-sensitive relapsed serous ovarian cancer revealed that the initial improved median PFS compared with placebo (8.4 vs 4.8 months) did not impart an overall survival benefit. The randomized phase II Precedent Trial of EC145 and pegylated liposomal doxorubicin (PLD) versus PLD alone in subjects with platinumresistant ovarian cancer showed initial benefit. This was the first study to show that EC145 in combination with PLD improved PFS
doi:10.1016/j.ygyno.2012.05.005
and OS over standard therapy in patients with platinum resistant ovarian cancer. Endometrial carcinoma Preliminary results from The Cancer Genome Atlas (TCGA) project showed that both endometrioid and serous uterine cancers had more genomic instability than initially suspected. A cost-effectiveness analysis of selective versus routine lymphadenectomy in presumed early endometrial cancer showed routine removal to be more costeffective. A second analysis concluded that lymphadenectomy could be omitted in low risk patients (preoperative grade 1 or 2, size ≤ 2 cm), even in the setting of unavailable or unreliable frozen section, as no patients in this subgroup had nodal recurrences. New phase II data in advanced or recurrent endometrial cancer included the results from the GOG 229G combination of bevacizumab and temsirolimus. The response rate in this pretreated population was acceptable (25%), but toxicity was moderate including rectovaginal fistula, bowel perforation and three associated deaths. Cervical carcinoma A phase II trial combining the biological agent erolitinib with chemo-radiation for stage IIB-IIIB cervical cancer was superior to historical controls, with 94% complete responses. A phase II trial of neoadjuvant chemotherapy with cisplatin and paclitaxel for locally advanced disease, followed by radical surgery and an additional six chemotherapy cycles showed promising results in both nodenegative and node-positive patients, with five year OS of 78%. Oncofertility Treatment with high-dose MPA for atypical hyperplasia or low grade endometrial cancer allowed 42 pregnancies in 155 women in a retrospective cohort. Post-pregnancy surveillance was essential in patients with cancer not undergoing subsequent hysterectomy, as the relapse rate within 5 years was 73%. In women with serous borderline tumors who received fertility-sparing treatment, a retrospective review showed an increased risk for recurrence (35% versus 15%), but no difference in overall survival. Nodal involvement was not associated with increased recurrence risk. Morbidity issues A prospective evaluation of aggressive control of hyperglycemia with continuous insulin infusion at one institution decreased surgical site infections by 40%. A SEER data review demonstrated that cardiac
4
Conference Report
death is the most significant mortality determinant for endometrial cancer patients, and that management of cardiac risk factors was likely the most crucial post-treatment intervention. Cutting edge science Preliminary results from the GOG 209 randomized phase III non-inferiority trial of first line chemotherapy for metastatic or recurrent endometrial showed that the combination of paclitaxel and carboplatin (TC) was not inferior to the combination of doxorubicin, cisplatin and paclitaxel (TAP). The phase II results of GOG 251 showed bevacizumab to be an active regimen for recurrent sex cord stromal tumors, with partial response in 17% and stable disease in 78%. Drug development in ovarian cancer Clinical outcomes of 122 patients with gynecologic malignancies enrolled on 30 phase I trials at one institution over a 12 year period
dispelled the myths of a high rate of toxicity and low rate of clinical benefits. Phase I outcomes for the novel topoisomerase inhibitor belotecan and oral etoposide in seven patients with platinumresistant ovarian cancer include four objectives and two complete responses. Early activity was also shown for the combination of the PARP inhibitor veliparib and liposomal doxorubicin in recurrent ovarian cancer. Finally, a modified intraperitoneal regimen for primary treatment with day one intravenous paclitaxel and bevacizumab followed by day two intraperitoneal cisplatin appears active, with 42 month PFS and mild cumulative neuropathy as the primary toxicity.
Eric L. Eisenhauer The Ohio State University Medical Center, USA Jean A. Hurteau University of Chicago Pritzker School of Medicine, USA