Successfully reported this slideshow.
We use your LinkedIn profile and activity data to personalize ads and to show you more relevant ads. You can change your ad preferences anytime.
The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Ins...
Outline
§ Primary tumor sidedness in colorectal cancer
§  CALGB/SWOG 80405
§ Immunotherapy in colorectal and anal cancer
§...
Primary Tumor
Sidedness in
Colorectal
Cancer (CRC)
3
Impact of primary tumor location on
Overall Survival and Progression Free Survival
in patients with metastatic colorectal ...
CALGB/SWOG 80405
Chemo + Cetuximab
Chemo + Bevacizumab
1ST LINE
MET / ADVANCED
COLORECTAL
KRAS wt
FOLFIRI
or
FOLFOX
MD cho...
CALGB 80405: Side of primary tumor
Methods
•  Population
–  KRAS wt pts in main analysis
–  Pre-amendment KRAS mut pts
•  ...
Presented by:
80405: Side of Primary Tumors
LEFT
N = 732
(68%)
RIGHT
N = 293
(27%)
TRANSVERSE N = 66
COULD NOT
DETERMINE
N...
Bettington, et al. Histopathology. 2013.
Embryology: The origin of the colon
RIGHT COLON
LEFT COLON
80405: Overall Survival by Sidedness
Presented by:
Side N (Events)
Median
(95% CI)
HR
(95% CI)
p
Left 732 (550)
33.3
(31.4...
80405: OS by Sidedness (Bevacizumab)
Presented by:
Side N (Events)
Median
(95% CI)
HR(95% CI) p
Left 356 (280)
31.4
(28.3-...
80405: OS by Sidedness (Cetuximab)
Presented by:
Side N (Events)
Median
(95% CI)
HR
(95% CI)
p
Left 376 (270)
36.0
(32.6-4...
80405: Sidedness is Prognostic
Overall Survival (OS)
Presented by:
KRAS wt
N = 1025
Right 1°
Median OS
(mos)
Left 1°
Media...
80405: Overall Survival by Sidedness and Biologic
Presented by:
31.4 (28.3-33.6)
36.0 (32.6-40.3)
24.2 (17.9-30.3)
16.7 (1...
Summary of Primary Tumor Sidedness in mCRC
§ Patients with R-sided primaries had much worse
outcomes than pts with L-sided...
Immunoscore in
Early Stage
Colon Cancer
15
Slide 1
Presented By Jerome Galon at 2016 ASCO Annual Meeting
Slide 6
Presented By Jerome Galon at 2016 ASCO Annual Meeting
Slide 11
Presented By Jerome Galon at 2016 ASCO Annual Meeting
Slide 14
Presented By Jerome Galon at 2016 ASCO Annual Meeting
Slide 18
Presented By Jerome Galon at 2016 ASCO Annual Meeting
Slide 22
Presented By Jerome Galon at 2016 ASCO Annual Meeting
Summary of Immunoscore in Early Stage Colon CA
§ Time to recurrence was significantly longer in patients
with stage I/II/I...
Pembrolizumab
in MSI-H mCRC
23
Slide 1
Presented By Dung Le at 2016 ASCO Annual Meeting
Slide 2
Presented By Dung Le at 2016 ASCO Annual Meeting
Slide 5
Presented By Dung Le at 2016 ASCO Annual Meeting
Slide 8
Presented By Dung Le at 2016 ASCO Annual Meeting
Slide 11
Presented By Dung Le at 2016 ASCO Annual Meeting
Slide 15
Presented By Dung Le at 2016 ASCO Annual Meeting
Slide 18
Presented By Dung Le at 2016 ASCO Annual Meeting
Slide 19
Presented By Dung Le at 2016 ASCO Annual Meeting
Summary of Pembrolizumab in MSI-H mCRC
§ PD-1 blockade with pembrolizumab is highly active
in dMMR mCRC
§ Complete and dur...
Nivolumab +/-
Ipilimumab in
mCRC
33
Nivolumab ± Ipilimumab in Treatment of Patients With Metastatic Colorectal Cancer With and Without High Microsatellite Ins...
Ipilimumab and Nivolumab <br />Mechanisms of Action
Presented By Michael Overman at 2016 ASCO Annual Meeting
Phase 2 CheckMate 142 Study Design: Microsatellite Stable (MSS) Cohort
Presented By Michael Overman at 2016 ASCO Annual Me...
Phase 2 CheckMate 142 Study Design: <br />MSI-H Cohort
Presented By Michael Overman at 2016 ASCO Annual Meeting
Investigator-Assessed Best Overall Response in <br />Patients With MSI-H Receiving Nivolumab Monotherapy
Presented By Mich...
Investigator-Assessed Best Overall Response in <br />Patients With MSI-H Receiving Nivolumab + Ipilimumab
Presented By Mic...
Best Reduction in Target Lesion Size <br />in Patients With MSI-H
Presented By Michael Overman at 2016 ASCO Annual Meeting
OS in Patients With MSI-H<br />Nivolumab ± Ipilimumab in Metastatic CRC
Presented By Michael Overman at 2016 ASCO Annual M...
Treatment-Related Adverse Events <br />in ≥ 15% of Patients With MSI-H
Presented By Michael Overman at 2016 ASCO Annual Me...
<br />Summary of Efficacy in Patients With MSS<br />Nivolumab ± Ipilimumab in Metastatic CRC
Presented By Michael Overman ...
Summary of Nivo +/- Ipi in mCRC
§ Nivolumab monotherapy and nivo + ipi showed
encouraging activity in MSI-H mCRC (interim ...
Cobimetinib +
Atezolizumab in
MSS mCRC
45
Clinical activity and safety of cobimetinib and atezolizumab in colorectal cancer
Presented By Johanna Bendell at 2016 ASC...
Slide 3
Presented By Johanna Bendell at 2016 ASCO Annual Meeting
Atezolizumab: An Anti-PDL1 Antibody
Presented By Johanna Bendell at 2016 ASCO Annual Meeting
PD-L1 and MEK Inhibition: A Rational Combination
Presented By Johanna Bendell at 2016 ASCO Annual Meeting
Phase Ib Dose Escalation and Cohort Expansion Study (NCT01988896)
Presented By Johanna Bendell at 2016 ASCO Annual Meeting
Safety Summary
Presented By Johanna Bendell at 2016 ASCO Annual Meeting
Safety: Treatment-related AEs
Presented By Johanna Bendell at 2016 ASCO Annual Meeting
Efficacy: Confirmed Objective Response
Presented By Johanna Bendell at 2016 ASCO Annual Meeting
Efficacy: Change in Tumor Burden
Presented By Johanna Bendell at 2016 ASCO Annual Meeting
Efficacy: Duration of Treatment and Response
Presented By Johanna Bendell at 2016 ASCO Annual Meeting
Summary of Cobi + Atezo in MSS mCRC
§ Cobimetinib + atezolizumab was fairly tolerated in
pts with refractory MSS mCRC
§ Co...
Nivolumab in
Metastatic Anal
Cancer
57
NCI9673: A Multi-Institutional ETCTN
Phase II Study of Nivolumab in Refractory
Metastatic Squamous Cell Carcinoma of
the A...
•  Approximately 80-95% of cases
are linked to infection with human
papillomavirus (HPV).
•  The role of HPV in the
tumori...
NCI#9673: Phase II Design of Nivolumab in Metastatic SCCA
Presented by: Cathy Eng, MD
Patients with metastatic squamous ce...
Primary Endpoint: Response Rate
Presented by: Cathy Eng, MD
Response Rate N (%)
CR 2 (5.4%)
PR 7 (18.9%)
SD 17 (45.9%)
PD ...
-1 0 0
-9 0
-8 0
-7 0
-6 0
-5 0
-4 0
-3 0
-2 0
-1 0
0
1 0
2 0
3 0
4 0
5 0
6 0
7 0
8 0
9 0
1 0 0
P a tie n t
%targetlesionr...
NCI#9673 Toxicities of Therapy
Toxicity (N=37) Grade (%)
1 2 3 4
Fatigue 17 (46) 7 (19) 1 (3) -
Anemia 13 (35) 11 (30) 2 (...
Summary of Nivolumab in Anal Cancer
§ First prospective phase II trial completed in refractory
mSCC of anal canal; <6 mont...
Thank You
To learn more about Ohio State’s cancer
program, please visit cancer.osu.edu or
follow us in social media:
65
Upcoming SlideShare
Loading in …5
×

ASCO Review 2016 Colorectal Cancer

By Kristen K. Ciombor, MD, MSCI

Related Books

Free with a 30 day trial from Scribd

See all

Related Audiobooks

Free with a 30 day trial from Scribd

See all

ASCO Review 2016 Colorectal Cancer

  1. 1. The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute Updates in Colorectal Cancer 2016 Kristen K. Ciombor, MD, MSCI Assistant Professor Division of Medical Oncology
  2. 2. Outline § Primary tumor sidedness in colorectal cancer §  CALGB/SWOG 80405 § Immunotherapy in colorectal and anal cancer §  Immunoscore in early stage colon cancer §  Pembrolizumab in MSI-H mCRC §  Nivolumab +/- ipilimumab in mCRC §  Cobimetinib + atezolizumab in MSS mCRC §  Nivolumab in metastatic anal cancer 2
  3. 3. Primary Tumor Sidedness in Colorectal Cancer (CRC) 3
  4. 4. Impact of primary tumor location on Overall Survival and Progression Free Survival in patients with metastatic colorectal cancer: Analysis of CALGB/SWOG 80405 (Alliance) A Venook, D Niedzwiecki, F Innocenti, B Fruth, C Greene, BH O’Neil, J Shaw, J Atkins, LE Horvath, B Polite, JA Meyerhardt, EM O’Reilly, R Goldberg, HS Hochster, CD Blanke, R Schilsky, RJ Mayer, M Bertagnolli, HJ Lenz for SWOG and the ALLIANCE
  5. 5. CALGB/SWOG 80405 Chemo + Cetuximab Chemo + Bevacizumab 1ST LINE MET / ADVANCED COLORECTAL KRAS wt FOLFIRI or FOLFOX MD choice ASCO, JUNE, 2014 Chemo + Cetuximab OS = 32.0 mos PFS = 11.4 mos Chemo + Bevacizumab OS = 31.2 mos PFS = 11.3 mosN = 1137 CONCLUSION: NO DIFFERENCE OS better than anticipated in both arms: Treatment effect and/or Patient selection All RAS wt ESMO, SEP, 2014 N = 526
  6. 6. CALGB 80405: Side of primary tumor Methods •  Population –  KRAS wt pts in main analysis –  Pre-amendment KRAS mut pts •  Data extraction –  Study chart, other supporting information if available •  Side of 1° determination –  Definitive information: •  Colonoscopy, surgical or imaging report Presented by:
  7. 7. Presented by: 80405: Side of Primary Tumors LEFT N = 732 (68%) RIGHT N = 293 (27%) TRANSVERSE N = 66 COULD NOT DETERMINE N = 46
  8. 8. Bettington, et al. Histopathology. 2013. Embryology: The origin of the colon RIGHT COLON LEFT COLON
  9. 9. 80405: Overall Survival by Sidedness Presented by: Side N (Events) Median (95% CI) HR (95% CI) p Left 732 (550) 33.3 (31.4-35.7) 1.55 (1.32-1.82)  < 0.0001 Right 293 (242) 19.4 (16.7-23.6) Right Left
  10. 10. 80405: OS by Sidedness (Bevacizumab) Presented by: Side N (Events) Median (95% CI) HR(95% CI) p Left 356 (280) 31.4 (28.3-33.6) 1.32 (1.05-1.65)   0.01   Right 150 (121) 24.2 (17.9-30.3) LeftRight
  11. 11. 80405: OS by Sidedness (Cetuximab) Presented by: Side N (Events) Median (95% CI) HR (95% CI) p Left 376 (270) 36.0 (32.6-40.3) 1.87 (1.48-2.32)   <0.0001   Right 143 (121) 16.7 (13.1-19.4) Left Right
  12. 12. 80405: Sidedness is Prognostic Overall Survival (OS) Presented by: KRAS wt N = 1025 Right 1° Median OS (mos) Left 1° Median OS (mos) Hazard Ratio 95% CI (adjusted*) P (adjusted*) All pts 19.4 33.3 1.55 (1.32,1.82) P < 0.0001 Cet 16.7 36.0 1.87 (1.48, 2.32) P < 0.0001 Bev 24.2 31.4 1.32 (1.05, 1.65) P = 0.01 *Adjusted for biologic, protocol chemotherapy, prior adjuvant therapy, prior RT, age, sex, synchronous disease, in place primary, liver metastases 19.3 MONTHS IS A BIG DIFFERENCE !!
  13. 13. 80405: Overall Survival by Sidedness and Biologic Presented by: 31.4 (28.3-33.6) 36.0 (32.6-40.3) 24.2 (17.9-30.3) 16.7 (13.1-19.4)
  14. 14. Summary of Primary Tumor Sidedness in mCRC § Patients with R-sided primaries had much worse outcomes than pts with L-sided primaries, independent of biologic arm (prognostic) § 1st line cetuximab and bevacizumab have different treatment effects in sidedness subgroups § Sidedness is likely a surrogate for tumor biology § Future trials to stratify patients by primary sidedness § Remember: this is a retrospective ad hoc analysis; these results will factor in when making tx decisions but this is not the whole story 14
  15. 15. Immunoscore in Early Stage Colon Cancer 15
  16. 16. Slide 1 Presented By Jerome Galon at 2016 ASCO Annual Meeting
  17. 17. Slide 6 Presented By Jerome Galon at 2016 ASCO Annual Meeting
  18. 18. Slide 11 Presented By Jerome Galon at 2016 ASCO Annual Meeting
  19. 19. Slide 14 Presented By Jerome Galon at 2016 ASCO Annual Meeting
  20. 20. Slide 18 Presented By Jerome Galon at 2016 ASCO Annual Meeting
  21. 21. Slide 22 Presented By Jerome Galon at 2016 ASCO Annual Meeting
  22. 22. Summary of Immunoscore in Early Stage Colon CA § Time to recurrence was significantly longer in patients with stage I/II/III colon cancer and high immunoscore § Immunoscore is significant in multivariate analyses in all cohorts (TS, IVS, EVS) § Potential identification of a high-risk stage II group § Immunoscore predicts TTR, DFS and OS § How much is microsatellite instability contributing? § Future immune-based assay for cancer: TNM-Immune? 22
  23. 23. Pembrolizumab in MSI-H mCRC 23
  24. 24. Slide 1 Presented By Dung Le at 2016 ASCO Annual Meeting
  25. 25. Slide 2 Presented By Dung Le at 2016 ASCO Annual Meeting
  26. 26. Slide 5 Presented By Dung Le at 2016 ASCO Annual Meeting
  27. 27. Slide 8 Presented By Dung Le at 2016 ASCO Annual Meeting
  28. 28. Slide 11 Presented By Dung Le at 2016 ASCO Annual Meeting
  29. 29. Slide 15 Presented By Dung Le at 2016 ASCO Annual Meeting
  30. 30. Slide 18 Presented By Dung Le at 2016 ASCO Annual Meeting
  31. 31. Slide 19 Presented By Dung Le at 2016 ASCO Annual Meeting
  32. 32. Summary of Pembrolizumab in MSI-H mCRC § PD-1 blockade with pembrolizumab is highly active in dMMR mCRC § Complete and durable responses are seen in >50% of patients § 18% have reached the two year mark on tx and patients are under surveillance § Next/current trials: single agent pembrolizumab in 1st line MSI-H mCRC, adjuvant trial, pembro + FOLFOX 32
  33. 33. Nivolumab +/- Ipilimumab in mCRC 33
  34. 34. Nivolumab ± Ipilimumab in Treatment of Patients With Metastatic Colorectal Cancer With and Without High Microsatellite Instability: <br />CheckMate 142 Interim Results Presented By Michael Overman at 2016 ASCO Annual Meeting
  35. 35. Ipilimumab and Nivolumab <br />Mechanisms of Action Presented By Michael Overman at 2016 ASCO Annual Meeting
  36. 36. Phase 2 CheckMate 142 Study Design: Microsatellite Stable (MSS) Cohort Presented By Michael Overman at 2016 ASCO Annual Meeting
  37. 37. Phase 2 CheckMate 142 Study Design: <br />MSI-H Cohort Presented By Michael Overman at 2016 ASCO Annual Meeting
  38. 38. Investigator-Assessed Best Overall Response in <br />Patients With MSI-H Receiving Nivolumab Monotherapy Presented By Michael Overman at 2016 ASCO Annual Meeting
  39. 39. Investigator-Assessed Best Overall Response in <br />Patients With MSI-H Receiving Nivolumab + Ipilimumab Presented By Michael Overman at 2016 ASCO Annual Meeting
  40. 40. Best Reduction in Target Lesion Size <br />in Patients With MSI-H Presented By Michael Overman at 2016 ASCO Annual Meeting
  41. 41. OS in Patients With MSI-H<br />Nivolumab ± Ipilimumab in Metastatic CRC Presented By Michael Overman at 2016 ASCO Annual Meeting
  42. 42. Treatment-Related Adverse Events <br />in ≥ 15% of Patients With MSI-H Presented By Michael Overman at 2016 ASCO Annual Meeting
  43. 43. <br />Summary of Efficacy in Patients With MSS<br />Nivolumab ± Ipilimumab in Metastatic CRC Presented By Michael Overman at 2016 ASCO Annual Meeting
  44. 44. Summary of Nivo +/- Ipi in mCRC § Nivolumab monotherapy and nivo + ipi showed encouraging activity in MSI-H mCRC (interim analysis) § Responses were durable in MSI-H patients § Tolerable safety profiles but increasing toxicities with combination therapy, consistent w/ observations in other solid tumors § Need final analysis prior to next trials 44
  45. 45. Cobimetinib + Atezolizumab in MSS mCRC 45
  46. 46. Clinical activity and safety of cobimetinib and atezolizumab in colorectal cancer Presented By Johanna Bendell at 2016 ASCO Annual Meeting
  47. 47. Slide 3 Presented By Johanna Bendell at 2016 ASCO Annual Meeting
  48. 48. Atezolizumab: An Anti-PDL1 Antibody Presented By Johanna Bendell at 2016 ASCO Annual Meeting
  49. 49. PD-L1 and MEK Inhibition: A Rational Combination Presented By Johanna Bendell at 2016 ASCO Annual Meeting
  50. 50. Phase Ib Dose Escalation and Cohort Expansion Study (NCT01988896) Presented By Johanna Bendell at 2016 ASCO Annual Meeting
  51. 51. Safety Summary Presented By Johanna Bendell at 2016 ASCO Annual Meeting
  52. 52. Safety: Treatment-related AEs Presented By Johanna Bendell at 2016 ASCO Annual Meeting
  53. 53. Efficacy: Confirmed Objective Response Presented By Johanna Bendell at 2016 ASCO Annual Meeting
  54. 54. Efficacy: Change in Tumor Burden Presented By Johanna Bendell at 2016 ASCO Annual Meeting
  55. 55. Efficacy: Duration of Treatment and Response Presented By Johanna Bendell at 2016 ASCO Annual Meeting
  56. 56. Summary of Cobi + Atezo in MSS mCRC § Cobimetinib + atezolizumab was fairly tolerated in pts with refractory MSS mCRC § Combination therapy resulted in higher clinical response rate (17%) and 6-month OS (72%) than expected with either agent alone § Cobi may sensitize tumors to atezo by increasing MHC I expression on tumor cells, promoting intratumoral CD8 T cell accumulation § Next/current trial: Phase Ib expansion and phase III trial both ongoing 56
  57. 57. Nivolumab in Metastatic Anal Cancer 57
  58. 58. NCI9673: A Multi-Institutional ETCTN Phase II Study of Nivolumab in Refractory Metastatic Squamous Cell Carcinoma of the Anal Canal (SCCA) V. Morris1, K. Ciombor2, M.E. Salem3, H. Nimeiri4, S. Iqbal5, P. Singh6, B. Polite7, D. Deming8, E. Chan9, J.L. Wade10, T.S. Bekaii-Saab2, H.E. Uronis11, M.G. Pasia1, G. Bland1, R.A. Wolff1, A. Ohinata1, C. Ohaji1, J.E. Rogers1, P. Sharma1, C. Eng1 1The University of Texas MD Anderson Cancer Center, Houston, TX; 2The Ohio State University Comprehensive Cancer Center, Arthur G. James Cancer Hospital, Columbus, OH; 3Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC; 4Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago, IL; 5University of Southern California/ Norris Comprehensive Cancer Center, Los Angeles, CA; 6Washington University, Siteman Cancer Center, St. Louis, MO; 7The University of Chicago, Chicago, IL; 8University of Wisconsin Hospitals and Clinics, Madison, WI; 9Vanderbilt University Medical Center, Nashville, TN; 10Cancer Care Center of Decatur, Decatur, IL; 11Duke University Medical Center, Durham, NC
  59. 59. •  Approximately 80-95% of cases are linked to infection with human papillomavirus (HPV). •  The role of HPV in the tumorigenesis of SCCA provides rationale for the use of immune checkpoint blockade agents as a novel therapy for treatment of patients with a virally driven disease. Presented by: Cathy Eng, MD Rationale for Nivolumab in Metastatic SCCA: Morris VK et al. The Oncologist, 2015, Sarup-Hansen E et al. J Clin Oncol ,2014
  60. 60. NCI#9673: Phase II Design of Nivolumab in Metastatic SCCA Presented by: Cathy Eng, MD Patients with metastatic squamous cell carcinoma of the anal canal - Treated with at least one prior therapy for metastatic disease - No prior immune therapies received as part of cancer treatment 12 patients treated initially with nivolumab 3mg/kg IV every 2 weeks Patients will be followed for best response using RECIST criteria 1.1 0 responses ≥1 response Stop trial Expand trial to include 25 additional patients with metastatic SCCA * HIV+ patients allowed •  Rapid enrollment in < 6 months •  Closed to enrollment as of 11/01/15 •  Simon Optimal, two- stage phase II study, Ho: p ≤ 0.05 and an alternative hypothesis Ha: p ≥ 0.20, •  α = 0.10 and a β = 0.10
  61. 61. Primary Endpoint: Response Rate Presented by: Cathy Eng, MD Response Rate N (%) CR 2 (5.4%) PR 7 (18.9%) SD 17 (45.9%) PD 8 (21.6%) Unevaluable 3 (8.1%) ORR (ITT, N=37) 9 (24.3%) ORR (Evaluable, N=34) 9 (26.5%) Data cutoff date: 5/15/16
  62. 62. -1 0 0 -9 0 -8 0 -7 0 -6 0 -5 0 -4 0 -3 0 -2 0 -1 0 0 1 0 2 0 3 0 4 0 5 0 6 0 7 0 8 0 9 0 1 0 0 P a tie n t %targetlesionreduction frombaselinebyRECIST1.1 P ro g re s s iv e D is e a s e S ta b le D is e a s e P a rtia l R e s p o n s e P R P D NCI#9673: Response Rate N=37 (ITT) N=34 (evaluable for RR) 2 CR’s 7 PR’s Presented by: Cathy Eng, MD Patients CR
  63. 63. NCI#9673 Toxicities of Therapy Toxicity (N=37) Grade (%) 1 2 3 4 Fatigue 17 (46) 7 (19) 1 (3) - Anemia 13 (35) 11 (30) 2 (5) - Rash 8 (22) 2 (5) 1 (3) - Constipation 8 (22) 2 (5) - - Diarrhea 8 (22) - - - Anorexia 5 (14) 4 (11) - - Weight loss 5 (14) 1 (3) - - Arthralgia 3 (8) 3 (8) - - Hyperglycemia 3 (8) 1 (3) - - Lymphedema 1 (3) 1 (3) - - Pneumonitis - 1 (3) - - Nausea 2 (5) - - - Hypothyroidism 1 (3) 1 (3) 1 (3) - Presented by: Cathy Eng, MD
  64. 64. Summary of Nivolumab in Anal Cancer § First prospective phase II trial completed in refractory mSCC of anal canal; <6 month accrual § Encouraging response rates in a “rare” cancer with few treatment options for metastatic disease § Nivolumab was well tolerated, even in HIV+ patients § Future trial: amendment of NCI 9673—pilot of nivolumab + ipilimumab 64
  65. 65. Thank You To learn more about Ohio State’s cancer program, please visit cancer.osu.edu or follow us in social media: 65

×