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Highlights in the medical treatment of advanced ovarian cancer Prof. Silverio Tomao UU

Highlights in the medical treatment of advanced ovarian cancer Prof. Silverio Tomao UU. OVARIAN CANCER MORTALITY RATES 1930-1997. 80. Uterus. Breast. Pancreas. 70. Ovary. Stomach. 60. Lung & Bronchus. Colon & Rectum. 50. Rate per 100,000 Female Population. 40. 30. 20. Ovary.

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Highlights in the medical treatment of advanced ovarian cancer Prof. Silverio Tomao UU

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  1. Highlights in the medical treatment of advanced ovarian cancer Prof. Silverio Tomao UU

  2. OVARIAN CANCER MORTALITY RATES 1930-1997 80 Uterus Breast Pancreas 70 Ovary Stomach 60 Lung & Bronchus Colon & Rectum 50 Rate per 100,000 Female Population 40 30 20 Ovary 10 0 1930 1940 1950 1960 1970 1980 1990 1997 Year Greenlee RT, et al. CA Cancer J Clin 2001;51:15-36.

  3. EXTIMATED DEATHS FOR GYNAECOLOGIC TUMORS 2003 6% 18% 22% 54%

  4. Results in Advanced Ovarian Cancer • Overall response rate 75-80% • Clinical complete response 50-75% • Recurrence rate 6-12 mts 40-50% • Recurrence rate >12 mts 20-30% • Disease-free interval 18-24 mo • Median survival 28-56 mo • % Five-year survival 15-30%

  5. Katsumata N Lancet 2009

  6. Katsumata N Lancet 2009

  7. Rustin G Lancet 2010

  8. Rustin G Lancet 2010

  9. Pujade-Lauraine E JCO 2010

  10. Key findings • In patients with partially platinum-sensitive relapsed ovarian cancer (6-12 months), carboplatin-PLD was not inferior to carboplatin-paclitaxel with respect to PFS and was even found to besignificantly superior • 27% reduction in risk of recurrence (HR=0.73; p=0.004) • Overall survival data immature • Carboplatin-paclitaxel is associated with more severe toxicity including carboplatin hypersensitivity, alopecia, and persistent sensory neuropathy • Moderate, reversible HFS, and nausea/vomiting is more frequent with PLD Vasey et al. ESMO-ECCO 2009; Abstract 18LBA

  11. Key findings and conclusions • Carboplatin-paclitaxel is associated with more significant toxicities including more frequent carboplatin hypersensitivity, greater alopecia, and prolonged sensory neuropathy • Moderate, reversible hand-foot syndrome, mucositis, and nausea/vomiting is more frequent with carboplatin-PLD Conclusion: Carboplatin-PLD demonstrated a superior therapeutic index (risk/benefit ratio) compared with carboplatin-paclitaxel Vasey et al. ESMO-ECCO 2009; Abstract 18LBA

  12. Conclusions • In patients with partially platinum-sensitive recurrent ovarian cancer (6-12 months), CALYPSO is the first trial to show a superior therapeutic index of an experimental arm (carboplatin-PLD) compared to the current standard (carboplatin-paclitaxel) • These results parallel those of the whole intent-to-treat CALYPSO population (6-12 and >6 months) Vasey et al. ESMO-ECCO 2009; Abstract 18LBA

  13. Monk JCO 2010

  14. Poveda A Ann Oncol 2010

  15. Pemetrexed Pemetrexed has demonstrated preclinical activity against ovarian carcinoma cell lines in combination with cisplatin The overexpression of folate receptor alpha, an important folate transporter, has been observed as ovarian epithelial cells undergo malignant transformation Observations such as these indicated that pemetrexed may have clinical activity in ovarian carcinoma Kano Y Oncol Res 2006 Tomassetti A Cancer Res 2003

  16. Pemetrexed In Platinum-resistant In Platinum-resistant epithelial ovarian cancer available salvage therapies such as liposomal doxorubicin and topotecan have response rates of only 10–20% Mutch DG J Clin Oncol 2007 Bhoola S Obstet Gynecol 2006 Response rates of approximately 10% were observed with pemetrexed in Platinum-resistant epithelial ovarian cancer Pemetrexed has activity at parity with other approved agents in this setting Vergote I EJC 2009

  17. Pemetrexed In Platinum-resistant Phase II Evaluation of Pemetrexed in treatment of Recurrent or Persistent Platinum-Resistant Ovarian or Primary Peritoneal Carcinoma Pemetrexedat a dose of 900 mg/m2 One patient (2%) had a complete and nine patients (19%) hadpartial responses, with a median duration response of 8.4 months.Seventeen patients (35%) had stable disease for a median of4.1 months. Eighteen patients (38%) had increasing disease.PFS was 2.9 months and OS 11.4 months Miller DS J Clin Oncol 2009

  18. Pemetrexed In Platinum-sensitive epithelial ovarian cancerresponse rates are comparable to the results of other platinum doublets with the exception of the notable absence of complete responses The PFS time observed in this trial is comparable to the PFS time observed in the AGO study of the carboplatin and gemcitabine doublet Hematologic toxicities were higher than with carboplatin and pemetrexed in the intergroup study, but in ICON43 were similar Ursula A J Clin Oncol 2008 Parmar MK Lancet 2003 Pfisterer J J Clin Oncol 2006 Tomao F Expert Rev Anticancer Ther 2009

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