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June 2016 ASCO in Review #CRCWebinar
The webinar discusses advancements in colorectal cancer treatment, particularly focusing on immunotherapy, chemotherapy, and clinical trial results. Key studies highlighted include Checkmate-142, demonstrating promising results for nivolumab and ipilimumab, and other studies exploring combinations of cobimetinib and atezolizumab. The session emphasizes ongoing research and the importance of patient-specific treatment strategies in managing colorectal cancer.
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June 2016 ASCO in Review #CRCWebinar
- 1. 2016 ASCO InReview Our webinar will begin shortly. WELCOME!
- 2. • Speaker: Dr.Emily Chan • Archived Webinars: FightColorectalCancer.org/Webinars • AFTER THE WEBINAR: Expect an email with links to the material & a survey. If you fill it out, we’ll send you an “I booty” bracelet. • Ask a question in the panel on the RIGHT SIDE of your screen • Follow along via Twitter – use the hashtag #CRCWebinar Today’s Webinar:
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- 4. Disclaimer : The information andservices provided by Fight Colorectal Cancer are for general informational purposes only. The information and services are not intended to be substitutes for professional medical advice, diagnoses or treatment. If you are ill, or suspect that you are ill, see a doctor immediately. In an emergency, call 911 or go to the nearest emergency room. Fight Colorectal Cancer never recommends or endorses any specific physicians, products or treatments for any condition.
- 5. Speaker: Emily Chan, MD,PhD, Associate Professor of Medicine (Hematology/Oncology) Vanderbilt University Dr. Chan joined the faculty of the Vanderbilt-Ingram Cancer Center after finishing her Medical Oncology/Hematology fellowship training at Memorial Sloan-Kettering Cancer Center. At Vanderbilt, her clinical interest is in gastrointestinal malignancies, including cancers of the colon, rectum, anal canal, esophagus, stomach, small intestine, gallbladder, pancreas, liver, and bile duct. Her research interests reside in the development of more effective treatment regimens for these diseases, particularly colorectal cancer, and the identification of markers that may predict response to specific therapies.
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- 7. ASCO Colorectal Highlights Immunotherapy: Abstract 3501:CheckMate-142 Abstract 3502: Cobimetinib and Atezolizumab in CRC Chemotherapy: Abstract 3512: PRODIGE 14-ACCORD 21 Abstract 3521: STAR-01
- 8. Abstract 3501: CheckMate- 142:Nivolumab +/- ipilimumab in mCRC interim results • MSI-H is found in 4% of mCRC • High mutation burden • Increased neoantigen load • Nivolumab: Fully human IgG4 immune checkpoint inhibitor antibody. – Binds PD-1 receptors on T cells – Disrupts PD-L1/PD-L2 signaling to restore antitumor immunity • Ipilimumab: Anti CTLA-4 antibody • Nivolumab and ipilimumab enhance T cell antitumor activity through distinct but complementary mechanisms.
- 9. Abstract 3501: CheckMate- 142:Nivolumab +/- ipilimumab in mCRC interim results • Inclusion: – ECOG PS 0-1 – Disease progression after > 1 prior tx (MSI-H) or latest tx (all), or intolerance or refusal to take chemotherapy) – MSI status determined locally • Exclusion: – CNS involvement – Prior malignancy within 3 years – Active or history of autoimmune disease – Need for immunosuppressive medications – Prior tx targeting T cell costimulation or immune checkpoint pathways
- 10. Abstract 3501: CheckMate- 142:Nivolumab +/- ipilimumab in mCRC interim results • Independent safety cohort: MSS • Third line or later non MSI-H mCRC • Nivo 1 mg/kg + Ipi 1 mg/kg q3w x 4 then nivo 3 mg/kg q2 wk. N > 3 • If tolerable, 1:1 randomization to two different doses of nivo/ipi combination N=10 per arm
- 11. Abstract 3501: CheckMate- 142:Nivolumab +/- ipilimumab in mCRC interim results • MSI-H • Nivo 3 mg/kg q2w >7/19 =>stage 2 • Nivo 3 mg/kg + Ipi 1 mg/kg q3 weeks x 4 then nivo 3 mg/kg q2 weeks >7/19 =>stage 2
- 12. Abstract 3501: CheckMate-142: Nivolumab+/- ipilimumab in mCRC interim results • Primary endpoint was investigator assessed ORR • Secondary endpoint was independent radiology review committee assessed ORR • Exploratory endpoints: – Safety and tolerability – PFS – OS – Investigator assessed ORR in MSS – Biomarkers
- 13. Abstract 3501: CheckMate- 142:Nivolumab +/- ipilimumab in mCRC interim results Nivolumab 3 mg/kg (n=70) Nivolumab 3 mg/kg + ipilimumab 1 mg/kg (n=30) Continuing treatment, n (%) 47 (67.1) 18 (60.0) Not continuing treatment, n (%) 23 (32.9) 12 (40.0) Reasons for not continuing, n (%) Disease progression Study drug toxicity Withdrew consent/other Not reported 19 (27.1) 2 (2.9) 1 (1.4) 1 (1.4) 6 (20.0) 4 (13.3) 1 (3.3) 1 (3.3) MSI-H subjects:
- 14. Abstract 3501: CheckMate- 142:Nivolumab +/- ipilimumab in mCRC interim results Nivolumab 3 mg/kg (n = 47) Nivolumab 3 mg/kg + Ipilimumab 1 mg/kg (n = 27) ORR, n (%) (95% exact CI) 12 (25.5) (15.4, 38.1) 9(33.3) (18.6, 50.9) Complete response 0 0 Partial response 12 (25.5) 9 (33.3) Stable disease 14 (29.8) 14 (51.9) Progressive disease 17 (36.2) 3 (11.1) Unable to determine 4 (8.5) 0 Median time to response, mo (range) 2.12 (1.3-13.6) 2.73 (1.2-6.9) Median duration of response, mo (range) NE (0.0-15.2) NE (NE-NE) Investigator assessed best ORR in MSI-H patients
- 15. Abstract 3501: CheckMate-142: Nivolumab +/-ipilimumab in mCRC interim results Nivolumab 3 mg/kg (n = 70) Nivolumab 3 mg/kg + Ipilimumab 1 mg/kg (n = 30) PFS rate, % (95% CI) 6 mo 9 mo 12 mo 45.9 (29.8, 60.7) 45.9 (29.8, 60.7) 45.9 (29.8, 60.7) 66.6 (45.5, 81.1) NE NE Median PFS, mo (95% CI) 5.3 (1.5, NE) NE (3.4, NE) Investigator assessed PFS in MSI-H
- 16. Abstract 3501: CheckMate-142: Nivolumab +/-ipilimumab in mCRC interim results Nivolumab 3 mg/kg (n = 70) Nivolumab 3 mg/kg + Ipilimumab 1 mg/kg (n = 30) OS rate, % (95% CI) 6 mo 9 mo 12 mo 75.0 (58.5, 85.7) 65.6 (48.0, 78.6) 65.6 (48.0, 78.6) 85.1 (65.0, 94.2) 85.1 (65.0, 94.2) NE Median OS, mo (95% CI) 17.1 (8.6, NE) NE (NE, NE) OS in patients with MSI-H
- 17. Abstract 3501: CheckMate-142: Nivolumab +/-ipilimumab in mCRC interim results Nivolumab 1 mg/kg + Impilimumab 3 mg/kg (n = 10) Nivolumab 3 mg/kg + Ipilimumab 1 mg/kg (n = 10) ORR, n (%) 1 (10) 0 Median PFS, mo (95% CI) 2.28 (0.62, 4.40) 1.31 (0.89, 1.71) Median OS, mo (95% CI) 11.53 (0.62, NE) 3.73 (1.22, 5.62) Efficacy in patients with MSS
- 18. Abstract 3501: CheckMate- 142:Nivolumab +/- ipilimumab in mCRC interim results Event, n (%) Nivolumab 3 mg/kg (n = 70) Nivolumab 3 mg/kg + Ipilimumab 1 mg/kg (n = 30) Any grade Grade 3-4 Any grade Grade 3-4 Any event 41 (58.6)* 10 (14.3) 25 (83.3) 8 (26.7) Fatigue 13 (18.6) 1 (1.4) 6 (20.0) 0 Diarrhea 10 (14.3) 1 (1.4) 13 (43.3) 0 Pruritus 8 (11.4) 0 5 (16.7) 1 (3.3) Nausea 5 (7.1) 0 6 (20.0) 0 Pyrexia 3 (4.3) 0 7 (23.3) 0 Any event leading to discontinuation 4 (5.7) 2 (2.9) 4 (13.3) 4 (13.3) Treatment related AE’s in > 15% of patients with MSI-H * One grade 5 event of sudden death
- 19. Abstract 3501: CheckMate-142: Nivolumab+/- ipilimumab in mCRC interim results Event, n (%) Nivolumab 1 mg/kg + Ipilimumab 3 mg/kg (n = 10) Nivolumab 3 mg/kg + Ipilimumab 1 mg/kg (n = 10) Any grade Grade 3-4 Any grade Grade 3-4 Any event 8 (80.0) 7 (70.0) 8 (80.0) 3 (30.0) Diarrhea 4 (40.0) 1 (10.0) 2 (20.0) 0 Asthenia 3 (30.0) 2 (20.0) 1 (10.0) 0 Nausea 3 (30.0) 1 (10.0) 2 (20.0) 0 Pyrexia 3 (30.0) 0 2 (20.0) 0 Vomiting 3 (30.0) 1 (10.0) 1 (10.0) 0 Fatigue 2 (20.0) 0 2 (20.0) 1 (10.0) Dry skin 1 (20.0) 0 0 0 Cough 0 0 2 (20.0) 0 Any event leading to discontinuation 5 (50.0) 5 (50.0) 2 (20.0) 2 (20.0) Treatment related AE’s in > 15% of patients with MSS
- 20. Abstract 3502: Cobimetinib and Atezolizumabin CRC • Cobimetinib: Highly selective MEK1/2 inhibitor • Atezolizumab: Anti-PDL1 antibody MEK inhibition can result in intratumoral T cell accumulation and upregulation of MHC1 in cell lines MEK inhibitor + PDL1 inhibitor results in increased tumor regression in preclinical studies
- 21. Abstract 3502: Cobimetinib and Atezolizumabin CRC • Study design: 3 + 3 dose escalation in solid tumors • Predefined expansion cohort of KRAS mutated mCRC • mRCRC n = 23 • MSI-H: 0% • MSI-low or stable: 30% • Unknown: 70% • PD-L1 expression – IC2/3 17% – IC0/1 70% – Unknown 13%
- 22. Abstract 3502: Cobimetinib andAtezolizumab in CRC Patients with CRC (n = 23) Treatment related N (%) All grade 23 (100%) Grade 3 8 (35%) Grade 4 0 (0%) Grade 5 0 (0%) Serious 2 (9%) AEs leading to withdrawal from cobimetinib 4 (17%) AEs leading to withdrawal from atezolizumab 0 (0%) Treatment related SAEs included nausea, vomiting, CVA (n = 1 each)
- 23. Abstract 3502: Cobimetinib andAtezolizumab in CRC Treatment related Aes (>15% incidence) All grade Grade 3 Diarrhea 70% 9% Fatigue 52% 4% Dermatitis acneiform 44% 0% Rash 35% 4% Nausea 26% 4% Maculopapular rash 26% 4% Pruritus 26% 0% AST increased 22% 0% Blood creatine phosphokinase increased 22% 0% Edema peripheral 17% 0% Stomatitis 17% 0% Vomiting 17% 4% Total of 21 patients collectively reported rash, maculopapular rash and dermatitis acneiform. 9% were grade 3.
- 24. Abstract 3502: Cobimetiniband Atezolizumab in CRC: Efficacy Confirmed Response per RECIST v1.1 KRAS mutant CRC cohort (n = 20) All CRC patients (n = 23) ORR (95% CI) 20% (5.7, 43.7) 17% (5.0, 38.8) PR 20% 17% SD 20% 17% PD 50% 52% NE 10% 9% Response did not correlate with PD-L1 status: IC0 (n=2), IC1 (n=1) and IC3 (n=1)
- 25. Abstract 3502: Cobimetiniband Atezolizumab in CRC: Efficacy KRAS mutant CRC cohort (n = 20) All CRC patients (n = 23) Median PFS (95% CI) 2.3 mo (1.8, 9.5) 2.3 mo (1.8, 9.5) 6 mo PFS (95% CI) 39% (0.16, 0.61) 35% (0.14, 0.56) Median OS (95% CI) NE (6.5, NE) NE (6.5, NE) 6 mo OS (95% CI) 77% (0.57, 0.97) 72% (0.52, 0.93)
- 26. Abstract 3512: PRODIGE14-ACCORD 21 •Randomized phase II study in mCRC with initially unresectable liver mets • Stratified by: RAS status, metastatic sites (lung mets y/n), causes of unresectability (surgical vs oncological) • Arm A: – A1: FOLFIRI + targeted therapy (n=56) – A2: FOLFOX4 + targeted therapy (n = 70) • Arm B: FOLFIRINOX + targeted therapy (n = 130) • Primary endpoint: Increase rate of R0-R1 resection from 50% to 70% with Arm B
- 27. Abstract 3512: PRODIGE 14-ACCORD21 • R0/R1 resection rate: 45.2% in Arm A; 56.9% in Arm B. P = 0.062 • OS: Improved in Arm B (median NR vs 36 m, p = 0.048)
- 28. Abstract 3521: STAR- 01Final Results • STAR 01: • Locally advanced rectal cancer: Chemoradiation with 5- FU vs FOLFOX • FOLFOX: more toxicity but no improved pCR • 5 yr OS: No statistically significant improvement in 5 yr OS
- 29. Summary • Immunotherapy showspromise in MSI-H tumors • Challenge is to sensitize MSS patients. MEK inhibition in combination with PD-L1 inhibition looks promising. • Chemotherapy: More is sometimes better but not always.
- 30. Want More onASCO Research?! Read more about the research presented at ASCO 2016 here . In this blog, the Currently Incurable Scientist dives into his top 5 abstract picks from ASCO 2016: http://fightcolorectalcancer.org/research- treatment/currently-incurable-scientist/asco-2016-pre-conference- insights/ Also, check out the Fight CRC immunotherapy blog and immunotherapy video to learn more about this exciting new treatment and developing research: http://fightcolorectalcancer.org/research-treatment/crc- immunotherapy-blueprint-presented-at-aacr-2016/ https://www.youtube.com/watch?v=RhdnYdghPd4
- 31. Question & Answer: SNAPA #STRONGARMSELFIE Bayer HealthCare will donate $1 for every photo posted (up to $25,000). Flex a “strong arm” & post it to Twitter or Instagram! (Use the hashtag!)
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