Spire Healthcare Group Plc · LSE:SPI
Spire Healthcare — Technical Presentation (May 2012)
24 slides from Spire Healthcare's technical presentation, May 2012
Slide 1: Improving Outcomes for Women with Advanced Ovarian Cancer: The role of anti-VEGF Therapy
Improving Outcomes for Women with Advanced Ovarian Cancer: The role of anti-VEGF Therapy Spire Leeds Hospital May 2012 Dr Timothy Perren Consultant Medical Oncologist St James’s Institute of Oncology Leeds UK 1
Slide 2: Ovarian Cancer – Major advances in treatment
Ovarian Cancer – Major advances in treatment Alkylating agents Platinum-based (melphalan or cyclophosphamide) therapy Platinum/taxane Front-line therapy 20 Mortality per 100,000 women 15 10 I first treated ovarian cancer here 5 0 1975 1985 1995 2005 Year Jemal, et al. CA Cancer J Clin 2009 2
Slide 3: Ovarian Cancer - rationale for development of new treatments
Ovarian Cancer - rationale for development of new treatments Ovarian cancer treatment remains a challenge ‒ Fourth most common cause of cancer-related death in women, 200 000 cases and 125 000 deaths/year worldwide Despite a good response to surgery and platinum-based chemotherapy, >50% of women wil
Slide 4: VEGF plays a key role throughout angiogenesis
Vascular endothelial growth factor (VEGF) plays a key role throughout angiogenesis VEGF VEGF VEGF VEGF VEGF bFGF bFGF bFGF bFGF TGFβ-1 TGFβ-1 TGFβ-1 TGFβ-1 PLGF PLGF PLGF PD-ECGF PD-ECGF Pleiotrophin Angiogenesis is mediated primarily via the interaction of VEGF-A with VEGFR-21–3 Ovarian cancer is h
Slide 5: Bevacizumab in ovarian cancer
Bevacizumab in ovarian cancer Humanised monoclonal antibody that binds to and inhibits the biological activity of Vascular Endothelial Growth Factor (VEGF) VEGF is central to ovarian physiology Single-agent activity of bevacizumab in recurrent ovarian cancer2,3 Activity of bevacizumab in metastatic
Slide 6: Agents Targeting the VEGF Pathway
Agents Targeting the VEGF Pathway Antibodies inhibiting VEGF receptors Soluble VEGF receptors Antibodies inhibiting VEGF (VEGF-TRAP) (e.g. bevacizumab) ↑ Permeability VEGF Cation VEGF channel receptor-2 Small-molecules P– –P –P P– –P P– –P inhibiting VEGF receptors P– P– (TKIs) P– –P –P (e.g. PTK-78
Slide 7: Two front-line trials with similar but not identical designs
Two front-line trials with similar but not identical designs Carboplatin AUC 6 (C) GOG-02181 Paclitaxel 175 mg/m2 (P) Placebo I ● Stage III optimal (macroscopic) ● Stage III suboptimal R II ● Stage IV Bev 15 mg/kg Placebo (Oct 05 – Jun 09) III Bevacizumab 15 mg/kg 15 months ICON72 Carboplatin AUC 5
Slide 8: GOG-0218: Regulatory PFS analysis
GOG-0218: Regulatory PFS analysis (Censored for CA-125 and non-protocol therapy) Arm I Arm II Arm III CP + Pla CP + Bev CP + Bev 1.0 → Pla → Pla → Bev (n=625) (n=625) (n=623) 0.9 Median PFS, months 12.0 12.6 18.0 Stratified analysis HR 0.899 0.645 0.8 (95% CI) (0.775–1.044) (0.551–0.756) 0.7 One-sid
Slide 9: GOG-0218: Overall survival
GOG-0218: Overall survival Feb 2010 at time of final PFS analysis 1.0 0.9 0.8 Overall survival estimate 0.7 0.6 Arm I Arm II Arm III CP + Pla CP + Bev CP + Bev 0.5 → Pla → Pla → Bev (n=625) (n=625) (n=623) 0.4 156 150 138 Events, n (%) 0.3 (25.0) (24.0) (22.2) Median, months 39.3 38.7 39.7 0.2 HR, s
Slide 10: ICON7: Baseline characteristics
ICON7: Baseline characteristics Control Research Characteristic (n=764) (n=764) Median age, years (range) 57 (18–81) 57 (24–82) Origin of cancer, % Ovary (epithelial) 87 88 Histology, % Serous 69 69 Clear cell 8 9 FIGO stage, % I/IIA 10 9 IIB–IIIB 21 20 IIIC/IV 69 71 Debulking surgery/ ≤1 cm 72 73 r
Slide 11: ICON7: Updated PFS
ICON7: Updated PFS 1.00 Control Research Proportion alive without progression Events, n (%) 464 (61) 470 (62) Median, 17.4 19.8 months Log-rank test p=0.039 0.75 HR (95% CI) 0.87 (0.77–0.99) 0.50 0.25 17. 19. 4 8 0 3 6 9 12 15 18 21 24 27 30 33 36 Number at risk Time (months) Control 764 693 474 350
Slide 12: ICON7: Updated progression-free survival by risk groups
ICON7: Updated progression-free survival by risk groups 12
Slide 13: ICON7: Updated Overall survival
ICON7: Updated Overall survival 1.00 0.75 Proportion alive 0.50 Control Research Events, n (%) 200 (26) 178 (23) Median, months Not yet reached Log-rank test p=0.11 0.25 HR (95% CI) 0.85 (0.69–1.04) 0 0 3 6 9 12 15 18 21 24 27 30 33 36 39 Number at risk Time (months) Control 764 741 724 703 672 646
Slide 14: ICON7: Updated overall survival (high-risk subgroup)
ICON7: Updated overall survival (high-risk subgroup) 1.00 0.75 Proportion alive 0.50 High-risk Control Research subgroup (n=234) (n=231) Deaths, n (%) 109 (47) 79 (34) 0.25 Median, months 28.8 36.6 Log-rank test p=0.002 HR (95% CI) 0.64 (0.48–0.85) 1-year OS rate (%) 86 92 0 0 3 6 9 12 15 18 21 24 2
Slide 15: ICON7: Overall survival by risk groups
ICON7: Overall survival by risk groups 1.00 Interaction: p=0.011 0.75 Control, low risk Research, low risk Proportion alive Control high risk 0.50 Research high risk Low-risk Control Research subgroup (n=530) (n=533) 0.25 Deaths, n (%) 91 (17) 99 (19) Median, months Not yet reached Log-rank test p=0
Slide 16: OCEANS: Study schema
OCEANS: Study schema Platinum-sensitive recurrent epithelial CG + Pla C AUC 4 ovarian, primary N=242 peritoneal or fallopian G 1000 mg/m2, d1 & 8 tube cancer • Measurable disease Placebo q3w until progression • ECOG 0/1 • No prior chemo for recurrent ovarian C AUC 4 cancer • No prior Bev G 1000 mg/m
Slide 17: OCEANS: Investigator-assessed PFS (primary analysis)
OCEANS: Investigator-assessed PFS (primary analysis) CG + Pla CG + Bev (n=242) (n=242) 1.0 Events, n (%) 187 (77.3) 151 (62.4) Median PFS, months 8.4 12.4 Proportion progression free 0.8 (95% CI) (8.31–9.66) (11.40–12.71) Stratified analysis HR 0.484 (95% CI) (0.388–0.605) 0.6 Log-rank p-value <0.00
Slide 18: Summary of safety: GOG-0218 and ICON7
Summary of safety: GOG-0218 and ICON7 a GOG-0218 ICON7 CP + Pla CP + Bev 15 → Pla → Bev CP CP + Bev 7.5 Grade ≥3 adverse event, % (N=601) (N=607) (N=763) (N=746) Hypertension 2.0 9.9 0.3 6.2 GI perforation 0.3 1.6 0.4 1.3 Fistula/abscess 0.8 1.3 0.7 0.8 Proteinuria 0.8 1.6 0.1 0.5 Wound-healing comp
Slide 19: Increased risk of high-grade hypertension with Avastin: a meta-analysis
Increased risk of high-grade hypertension with Avastin in cancer patients: a meta-analysis • 12,656 patients with a variety of tumours from 20 studies GOG-0218 Grade ≥2: 22.9% • Incidence: ICON7 – all-grade hypertension: 23.6% (95% CI: 20.5–27.1) All grades: 26% – high-grade (grade 3 or 4): 7.9% (95
Slide 20: How to prevent and detect hypertension?
How to prevent and detect hypertension? • Monitor blood pressure before Baseline treatment screening • Pre-existing hypertension should be adequately controlled before starting Avastin treatment1,2 No Hypertension hypertension • Prophylactic antihypertensive therapy is not recommended2 • Hypertensio
Slide 21: How to manage grade 2 hypertension
How to manage grade 2 hypertension • Hypertension can generally be well controlled with antihypertensive medication that must be initiated in case of persistent and/or symptomatic hypertension • Several options – angiotensin-converting enzyme (ACE) inhibitors – beta-blockers – calcium channel blocke
Slide 22: How to manage grade 3/4 hypertension?
How to manage grade 3/4 hypertension? • In patients with severe (grade 3) hypertension – temporary interruption of Avastin is recommended until adequate control is achieved – if hypertension cannot be controlled, Avastin should be permanently discontinued • Avastin should be discontinued in patients
Slide 23: Thromboembolic events do not appear to be significantly more common with Avastin
Thromboembolic events do not appear to be significantly more common with Avastin in ovarian cancer • Slight increment, but not significant, in the incidence of venous or arterial thromboembolic events in GOG-0218 or ICON7 • How should patients who experience thromboembolic events be managed? – Avast
Slide 24: Bevacizumab conclusions from trials
Bevacizumab conclusions from trials • Primary objective was met in both trials • Bevacizumab (with chemotherapy and continued as a single agent) significantly improved PFS in first line treatment and in platinum sensitive relapse. • Overall survival data (from ICON7) are not yet mature – However, su
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