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Nab-paclitaxel in Ovarian Cancer

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Presentation on theme: "Nab-paclitaxel in Ovarian Cancer"— Presentation transcript:

1 Nab-paclitaxel in Ovarian Cancer

2 Nab paclitaxel in Gynecologic Malignancy Trials
Study Description Principal Investigator Status Nab paclitaxel in Platinum-Sensitive Ovarian Cancer M. Teneriello 47 pts JCO 2009 Nab paclitaxel + Carboplatin in Platinum-Sensitive Ovarian Cancer B. B. Benigno 38 pts ASCO 2010 Nab paclitaxel in Recurrent or Persistent Platinum-Resistant Ovarian Cancer R. Coleman 51 pts Gyn Oncol 2011 Nab paclitaxel + Avastin in Recurrent Platinum-Resistant Ovarian Cancer T. Tillmanns 48 pts Nab-paclitaxel with GM-CSF as chemoimmunotherapy for Platinum-Resistant epithelial Ovarian Cancer R.E. Swensen 20 pts ASCO 2011

3 Measurable disease by RECIST or elevated CA-125 ( > 70 U/mL)
Key Eligibility Measurable disease by RECIST or elevated CA-125 ( > 70 U/mL) Prior platinum-based chemotherapy Platinum treatment-free interval >6 months n=47 Nab paclitaxel 260 mg/m2 on Day 1 q Q3W x 6 cycles or 8 cycles if patient achieved CR Primary endpoints: Response Rate Secondary endpoints: Progression Free and Overall Survival, Quality of Life, Safety Teneriello

4 Patient Characteristics
Number of Patients Enrolled 47 Age, mean (Range) 66 (42 – 84) n % ECOG Performance Status 1 38 9 81 19 Prior Therapy Prior taxane Prior Chemotherapy > 12 months Prior Chemotherapy < 12 months Surgery 42 43 4 44 90 92 94 Site of Primary Disease Epithelial Ovarian Fallopian Tube Peritoneum 37 79 2 Stage at Baseline IC/IIB/IIC III/IIIA/IIIB IIIC IV 7 25 11 15 52 23 Teneriello

5 Efficacy Data 64% Response Rate with Nab paclitaxel Monotherapy
Total Number of Eligible/Treated Subjects 44 n (%) 95% CI Best Response Complete Response Partial Response Stable Disease SD > 6 months SD < 6 months Progressive Disease Clinical Benefit (CR + PR + SD > 6 months) Non-evaluable* 15 (34%) 13 (30%) 14 (32%) 6 8 2 (5%) 34 (77%) 3 (20.1 – 48.1) (16.1 – 43.0) (18.1 – 45.6) (0 – 10.7) Time to Response, median (months) Range 1.3 (0.5 – 4.8) Duration of Response, median (months) 7.9 (2.7 – 17.6) (6.7 –10.5) Progression-free Survival, median (months) 8.5 Can we follow up with Teneriello to see where we are with PFS and overall survival??? Overall response rates were calculated using either Response Evaluation Criteria in Solid Tumors or CA-125 or both; the overall response rate (CR PR) was 64%. *Three patients were not assessable; two patients were found to be ineligible after start of treatment, and one other patient was never treated. Teneriello

6 Safety Data: Adverse Events
Most Common Grade 3/4 AEs All Grade n (%) Grade 3 Grade 4 Hematological Neutropenia 20 (47%) 6 (13%) 5 (11%) Leukopenia 7 (15%) -- Non-hematological Neuropathy 4 (9%) Fatigue 10 (22%) 1 (2%) Diarrhea 3 (7%) Abdominal pain 2 (4%) Pneumonia Upper respiratory tract infection Generalized weakness Alopecia 40 (87%) Teneriello

7 Conclusions Nab-paclitaxel is active in this group of patients with recurrent ovarian, peritoneal, or fallopian tube cancer. The ORR was 64%. Toxicities were manageable. Further studies of nab-paclitaxel in combination with platinum are warranted. Teneriello

8 Continue Nab paclitaxel until progressive disease or
Phase II Study of Nab paclitaxel® Plus Carboplatin in Patients with Recurrent Platinum-Sensitive Ovarian or Primary Peritoneal Cancer Key Eligibility Recurrent ovarian or primary peritoneal cancer Platinum-sensitive Measurable disease n = 40 Nab paclitaxel® 100 mg/m2 Days 1, 8, 15 q 28 days + Carboplatin AUC 5 or 6 Day 1 q 28 days x 6 cycles Continue Nab paclitaxel until progressive disease or PI-PT discretion Primary endpoints: Antitumor activity and safety Secondary endpoints: Progression-free survival and overall survival Benigno

9 Patient Characteristics
Number of Patients Enrolled 40 (38 evaluable) Age, mean (Range) 62 ( ) n % ECOG Performance Status 1 35 5 87 13 Prior Therapy Prior taxane / platinum Prior chemotherapy > 12 months Prior chemotherapy < 12 months 40 14 25 100 63 Site of Primary Disease Epithelial Ovarian Fallopian Tube 39 98 2 Stage at Baseline IIB / IIC / IIIB IIIC IV 9 28 3 23 70 7 Benigno

10 Dosing Information Carboplatin dose AUC 6 administered to first 9 patients After Grade 4 neutropenia in 3 patients, reduced carboplatin to AUC 5 20 patients discontinued treatment for reasons other than toxicity or disease progression Treatment Cycles Completed >18 cycles n (%) 13-17 cycles 7-12 cycles 6 cycles < 6 cycles Evaluable Patients 38 TOTAL 5 1 pt active 4 10 14 Reason for Discontinuing Phys or Pt discretion Progressive disease Toxicitiy Type/ cycle 2 6 3 1 (G4 neurotoxity cycle 6) (G4 pneumonia cycle 5, G3 hem cycle 4) Benigno

11 Safety Data: Adverse Events
Most Common Grade 3/4 AEs Grade 3 n (%) Grade 4 Hematological Neutropenia 14 (34%) 3 (7%) Anemia 4 (10%) -- Thrombocytopenia 2 (5%) Non-hematological Fatigue 13 (32%) Carboplatin reaction 7 (17%) Nausea Constipation 1 (2%) Fever Shortness of breath Neuropathy Benigno

12 Efficacy Data: Survival Over 50% of patients alive at 1-year
Survival Rates 1-Year 56% 2-Year 39% Survival based on Benigno data (23 alive at 1 year out of 41, 16 alive at 2 year out of 41) * Until 9/18/2009, there are 18 patients alive, 21 are dead and one is UNK due to lost of FU, one still active on cycle 44 Benigno

13 Conclusions With a 97% disease control rate (CR + PR + SD), the combination of nab-paclitaxel plus carboplatin had significant antitumor activity and was reasonably tolerated in patients with platinum-sensitive recurrent ovarian cancer. Benigno

14 Recurrent or persistent ovarian, peritoneal, fallopian tube carcinoma
Key Eligibility Recurrent or persistent ovarian, peritoneal, fallopian tube carcinoma Platinum-resistant or refractory Paclitaxel-resistant or refractory Measurable disease n = 51 Nab paclitaxel 100 mg/m2 on Days 1, 8, 15 q 28 Treatment until disease progression or unacceptable toxicity Primary endpoints: Antitumor activity and safety Secondary endpoints: Progression Free and Overall Survival Coleman

15 Patient Characteristics
Race: White 35 (74.5%) African American 9 (19.1%) Hispanic ( 4.3%) Am Indian ( 2.1%) Site of Disease Ovary 41 (87.2%) Fallopian Tube (2.1%) Other 5 (10.6%) Grade (14.9%) (4.3%) (80.9%) Cell Type: Serous Adeno 34 (72.3%) Age: (36.6%) (2.1%) (34.1%) (17 %) (12.2%) Performance Status: 0 31 (66.0%) 1 15 (31.9%) (2.1%) Prior Therapy 1 Reg. 47 (100%) Immunoth 2 Hormonal 2 Coleman

16 Efficacy Data 23% Response Rate with Nab paclitaxel Monotherapy
Responses reported in 47 of 51 patients: N % Responses CR+PR (1CR&10PR) 11 23 Stable Disease 17 36 Progressive Disease Coleman

17 Efficacy Data: Overall Survival and Progression-free Survival
Progression-free Survival, median: 4.5 months Overall survival, median: months Coleman

18 Safety Data: Adverse Events
No grade 4 toxicities Only 1 patient grade 3 neurosensory toxicity Toxicity / Adverse Events Maximum grade, no. of patients 1 2 3 4 Hematological anemia 19 20 0 (0%) neutropenia 5 6 leukopenia 15 11 thrombocytopenia Non-hematological neurosensory 14 constitutional gastrointestinal 8 metabolic pain 10 AE, adverse event Coleman

19 Conclusion The authors conclude that this data support the contention that weekly nab-paclitaxel is associated with significant clinical efficacy in highhly resistant ovarian cancer patients, and compared to weekly paclitaxel in this setting, may have a more favorable side effect profile. Coleman

20 Phase II Study of Nab paclitaxel® with Bevacizumab in Patients with Recurrent Platinum-Resistant Primary Epithelial Ovarian or Primary Peritoneal Cancer Key Eligibility Recurrent or persistent ovarian, peritoneal cancer Platinum-resistant within 6 months Measurable disease n = 48 Nab paclitaxel 100 mg/m2 on Days 1, 8, 15 + Bevacizumab 10 mg/kg Days 1, 15 Q 28 d Treatment until disease progression or unacceptable toxicity Primary endpoints: Duration of objective response, safety Secondary endpoints: Duration of progression-free survival, overall survival, quality of life Tillmanns

21 Efficacy Data 48% response rate with Nab paclitaxel + Bevacizumab
Stable Disease: 25% Best Overall Response Not Done PD PR SD Treatment Cycle n % 4 16 33.3 19 39.6 13 27.1 7 21 43.8 11 22.9 10 22 45.8 20.8 25 28 EOS All Pts 5 10.4 8 16.7 23 47.9 12 25.0 EOS Pts off study 1 26 20.5 18 46.1 30.8 Tillmanns

22 Efficacy: Progression-free Survival
Median Progression-free Survival: months Tillmanns

23 Safety Data: Grade 3 / 4 Adverse Events*
Most Common Grade 3/4 AEs* All Grade n (%) Grade 3 Grade 4 Hematological Neutropenia 13 (27%) 5 (10%) -- Anemia 11 (23%) 1 (2%) Non-hematological Abdominal pain 17 (35%) 3 (6%) Bowel obstruction 4 (8%) 2 (4%) Cardiac disorder Fatigue 35 (73%) GU / renal 7 (15%) Infections 8 (17%) Metabolism disorders 18 (38%) Other blood / lymphatic system disorders 16 (33%) Other gastrointestinal disorders 29 (60%) 6 (13%) Vascular disorders 12 (25%) Neuropathy 14 (29%) * One Death, NOS Tillmanns

24 Conclusions Nab-Paclitaxel 100 mg/m2 IV on days 1, 8, 15 in combination with bevacizumab 10 mg/kg IV on days 1 and 15 every 28 days appears to be highly active with impressive PFS and OS combined with low G3/G4 toxicity. Further prospective trials should be explored in this population. Tillmanns

25 A phase 2 trial of weekly nanoparticle paclitaxel with GM-CSF as chemoimmunotherapy for platinum-resistant epithelial ovarian cancer Phase II study to evaluate wkly nab-paclitaxel followed by GM-CSF in patients (n=30) with platinum-resistant ovarian cancer, primary peritoneal or fallopian tube cancer and elevated CA-125 Endpoints: ORR TTP on current study TTP on the prior platinum regimen Swensen

26 Treatment Nab-paclitaxel 100 mg/m² d 1,8,15 followed by Leukine 250 mcg/day d of 28 day cycle until progression or 6 cycles. Responding patients received up to 6 more cycles of Leukine d 14-28 Swensen

27 Results 20 patients received at least 1 dose study medication; 16 have completed the study: CR: 13% (2/16); PR: 50% (8/16) TTP (median): 110 days overall; 140 days for responders ; 269 days on prior platinum regimens Toxicities: Gr 3 lymphopenia: 3; Gr 3 neutropenia: 3; Gr 3 fatigue: 1; Gr 3 hypokalemia: 1; Gr 3 anemia: 1; One pt hospitalized for bowel obstruction, another with bowel obstruction, esophagitis and hypoxia due to pleural effusion. 2 pts went off study due to progressive sensory neuropathy. 2 pts died while on study Swensen

28 Conclusions Weekly nab-paclitaxel with GM-CSF induces a high response rate in platinum-resistant ovarian cancer with manageable toxicity. Current regimen did not prolong TTP vs. TTP on prior platinum regimen. Swensen

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