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GI ASCO single slide per page 1-17-15

Wafik El-Deiry, MD PhD FACP
Wafik El-Deiry, MD PhD FACP

This document summarizes a presentation on new anti-angiogenic therapies for metastatic colorectal cancer (mCRC). It discusses results from the phase III RAISE study of FOLFIRI +/- Ramucirumab in second-line treatment after FOLFOX + Bevacizumab, and a phase II randomized trial of single agent Famitinib in third-line treatment. The RAISE study found that adding Ramucirumab to FOLFIRI improved overall survival compared to FOLFIRI alone. The Famitinib trial did not find a difference in overall survival compared to placebo, though progression-free survival was prolonged. Biomarkers were identified that could help determine which patients are

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New anti-angiogenic therapy in mCRC: FOLFIRI +/- Ramucirumab in 2nd line after FOLFOX + Bevacizumab (phase III: RAISE study) or single agent Famitinib in 3rd line (phase II randomized with placebo) Wafik El-Deiry, MD, PhD, FACP Deputy Director for Translational Research Co-Leader, Molecular Therapeutics Program Fox Chase Cancer Center January 17, 2015 Oral Abstract Session: Cancers of the Colon, Rectum, and Anus
Learning Objectives ≒ Understand current use of anti-angiogenic therapy in mCRC ≒ Understand different anti-angiogenic therapeutic targets and agents in mCRC ≒ Explain and critique the RAISE phase III trial of Ramicirumab + FOLFIRI used in second line for mCRC ≒ Explain and critique the randomized phase II single agent Famitinib trial in 3rd line therapy of mCRC Presented by: Wafik El-Deiry, MD, PhD, FACP
Outline of Presentation ≒ Review angiogenesis as a therapeutic target ≒ Describe approved agents and agents under investigation ≒ Critically assess the Ramicirumab and Famitinib clinical trials in mCRC Presented by: Wafik El-Deiry, MD, PhD, FACP
Angiogenesis Presented by: Wafik El-Deiry, MD, PhD, FACP Clinical Observations in 1960s 2004 2001- 2015 Effectively translated in last two decades 1980s: VEGF
By 2010, many inhibitors tried in mCRC, most failed Presented by: Wafik El-Deiry, MD, PhD, FACP By 2010, there was no progress in angiogenesis inhibition beyond bevacizumab Regorafenib, VEGF-trap, Tie2, bFGF, angiopoietin inhibitors were being tested
Angiogenesis beyond VEGF in mCRC Presented by: Wafik El-Deiry, MD, PhD, FACP Phase III CORRECT Trial in mCRC Phase III VELOUR Trial in mCRC Regorafenib & Aflibercept approved in 2012 Targets include VEGFRs, Ang-2, PDGFR-硫, FGFR
Current NCCN Guidelines for mCRC Presented by: Wafik El-Deiry, MD, PhD, FACP NCCN Guidelines now include Ziv-aflibercept in 2nd line and regorafenib in 3rd line regimens
Presented by: Wafik El-Deiry, MD, PhD, FACP
Ramicurimab Presented by: Wafik El-Deiry, MD, PhD, FACP ≒ Ramicurimab is a fully humanized angiogenesis inhibitory antibody that targets VEGFR2 and prevents binding of VEGF ≒ Approved by FDA in April 2014 to treat gastric or GE junction cancer after it improved OS ≒ Known side-effects include diarrhea and hypertension VEGFR2
Presented by: Wafik El-Deiry, MD, PhD, FACP Ramicirumab was approved by the FDA in combination with docetaxel for NSCLC following progression on platinum- based therapy on December 12, 2014
Phase II study of Ramicurimab plus FOLFOX as frontline therapy in mCRC Presented by: Wafik El-Deiry, MD, PhD, FACP
RAISE Study of Ramicurimab Presented by: Wafik El-Deiry, MD, PhD, FACP ≒ A randomized, double- blind, multicenter phase III of FOLFIRI + Ramicurimab or placebo in patients with mCRC progression during or following FOLFOX + Bevacizumab N= 536 N= 536 1072 patients
RAISE: Ramicurimab + FOLFIRI in 2nd line mCRC after FOLFOX + Bevacizumab improved OS Presented by: Wafik El-Deiry, MD, PhD, FACP ≒ Lots of patients with WT KRAS (~50%) were eligible in both arms ≒ The two arms were well-matched at baseline ≒ Addition of Ramicurimab to FOLFIRI prolonged median overall survival by 13.3 months versus 11.7 months for FOLFIRI alone P = 0.0219 ≒ The most common grade 3/4 adverse events with ramicurimab were neutropenia, fatigue, hypertension and diarrhea Time (months) 0 3 6 9 12 15 18 21 24 27 30 33 36 39 42 OverallSurvival 0.0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1.0 Ramicurimab increased OS when added to FOLFIRI in 2nd line therapy of mCRC to 13.3 mo vs 11.7 mo for FOLFIRI alone Ramicurimab also increased PFS when added to FOLFIRI in 2nd line therapy of mCRC to 5.7 mo vs 4.5 mo for FOLFIRI alone (P = 0.0005) P = 0.0219 536 patients in each arm
3 Studies RAISE, TML, & VELOUR looked at anti-angiogenic therapy in the second line after first line CT + Bev Presented by: Wafik El-Deiry, MD, PhD, FACP FOLFOX + Bev ! FOLFIRI -/+ Ramicurimab FOLFOX or + Bev ! FOLFOX or -/+ Bev FOLFIRI FOLFIRI FOLFOX -/+ Bev ! FOLFIRI -/+ ziv-Aflibercept RAISE: TML: VELOUR: First Line Second Line
TML: Bevacizumab + FOLFIRI in 2nd line mCRC after FOLFOX or FOLFIRI + Bevacizumab improved OS Presented by: Wafik El-Deiry, MD, PhD, FACP ≒ Similar design as RAISE ≒ Similar outcomes for PFS/OS extension FOLFIRI FOLFIRI + Ramicurimab FOLFIRI/ FOLFOX FOLFIRI + bevacizumab PFS 4.5 5.7 4.1 5.7 OS 11.7 13.3 9.8 11.2 RAISE arms TML arms PFS and OS: median survival in months Not exactly the same: In TML patients had either FOLFOX or FOLFIRI in first line + bevacizumab and randomized to FOLFOX or FOLFIRI -/+ bevacizumab beyond progression TML TML PFSTML OS
VELOUR: Aflibercept + FOLFIRI in 2nd line mCRC after FOLFOX + Bevacizumab improved OS Presented by: Wafik El-Deiry, MD, PhD, FACP ≒ Similar design as RAISE ≒ Similar outcomes for OS extension FOLFIRI FOLFIRI + Ramicurimab FOLFIRI FOLFIRI + Aflibercept PFS 4.5 5.7 4.67 6.90 OS 11.7 13.3 12.06 13.5 RAISE arms VELOUR arms PFS and OS: median survival in months Not exactly the same: In VELOUR most patients had no prior Bevacizumab which may explain slightly lower PFS numbers in RAISE although it didnt seem to impact the OS data
VELOUR: Aflibercept + FOLFIRI in 2nd line mCRC after FOLFOX + Bevacizumab improved OS Presented by: Wafik El-Deiry, MD, PhD, FACP In VELOUR less than 1/3 of patients received prior Bevacizumab whereas in RAISE all patients received at least 2 doses of Bevacizumab
RAISE vs TML vs VELOUR summary of outcomes Presented by: Wafik El-Deiry, MD, PhD, FACP RAISE: TML: VELOUR: PFS -/+ OS -/+ 4.5/ 5.7 m 11.7/ 13.3 m 4.1/ 5.7 m 9.8/ 11.2 m 4.7/ 6.9 m 12.1/ 13.5 m ≒ Outcomes appear similar although designs not exactly the same ≒ Need randomized comparisons ≒ ? If there may be benefit from ziv or Ram beyond Bev & Ram or ziv (3rd line) ≒ ? If it may be worth trying to combine anti-angiogenics ≒ Was too toxic in RCC but is this universally true with all agent combinations? FOLFOX + Bev ! FOLFIRI -/+ Ramicurimab FOLFOX or + Bev ! FOLFOX or -/+ Bev FOLFIRI FOLFIRI FOLFOX -/+ Bev ! FOLFIRI -/+ ziv-Aflibercept First Line Second Line
RAISE Comments: Ramicurimab + FOLFIRI in 2nd line mCRC after FOLFOX + Bevacizumab Presented by: Wafik El-Deiry, MD, PhD, FACP ≒ Ramicurimab is effective to prolong OS in the second line therapy when combined with FOLFIRI after progression on FOLFOX plus Bevacizumab ≒ The combination was well-tolerated (with some added toxicities in the combo) ≒ Recap of some possible future directions: ≒ Ramicurimab + FOLFIRI vs Bev + FOLFIRI in 2nd line after FOLFOX + Bev ≒ Ramicurimab + FOLFIRI in patients with prior FOLFOX without Bev ≒ Ramicurimab + FOLFIRI vs anti-EGFR + FOLFIRI in 2nd line in WT KRAS population ≒ Single agent Ram in patients who cant tolerate chemo ≒ Ram or Ram + cape maintenance ≒ Ram + FOLFIRI vs Aflibercept + FOLFIRI in 2nd line with prior FOLFOX or FOLFOX + Bev ≒ Need biomarkers to predict best responders vs those less likely to benefit ≒ In 2015 need to assess and compare financial toxicities
Ramicurimab in gastric cancerposter at 2015 GI ASCO Presented by: Wafik El-Deiry, MD, PhD, FACP Potential to push dose of Ramicirumab to improve outcomes
A randomized, double-blind, parallel-group, placebo controlled, multi-center, phase II clinical study of Famitinib in the treatment of advanced metastatic colorectal cancer Rui-hua Xu*, Lin Shen*, Ke-ming Wang, Gang Wu, Chun-mei Shi, Ke-feng Ding, Li-zhu Lin, Jin-wan Wang, Jian-ping Xiong, Chang-ping Wu, Jin Li, Yun-peng Liu, Dong Wang, Yi Ba, Jue-ping Feng, Yu-xian Bai, Jing-Wang Bi, Li-wen MA, Jian Lei and Hao Yu *Co-Leading Principle Investigator Abstract No.513 Presented by: Rui-hua Xu
Famitinib targets Presented by: Wafik El-Deiry, MD, PhD, FACP KDR/VEGFR2 cKit PDGFR Anti-angiogenesis
Famitinib targets Presented by: Wafik El-Deiry, MD, PhD, FACP
Famitinib had efficacy in NPC phase II trial Presented by: Wafik El-Deiry, MD, PhD, FACP
Famitinib in mCRC Presented by: Wafik El-Deiry, MD, PhD, FACP ≒ 154 patients 2:1 randomization; groups well matched ≒ 1.3 mo prolongation of FPS (P = 0.0053) & 59.8% DCR ≒ Breakdown of prior therapies unclear; FOLFOX, FOLFIRI, cetuximab and bevacizumab are available in China ≒ No difference in OS noted ≒ AEs included proteinuria, neutropenia, HTN, thrombocytopenia, H/F syndrome and diarrhea PFS Data:
Regorafenib in mCRC Presented by: Wafik El-Deiry, MD, PhD, FACP ≒ 1052 patients 2:1 randomization; groups well matched ≒ 1.9 mo prolongation of FPS and 6.4 mo (Regoraf) vs 5.0 mo (placebo) OS OS/PFS Data: ≒ Subgroup analyses supported impact of Regorafenib on OS including KRAS mutant mCRC ≒ Lack of demonstrated effect on OS by Famitinib may be aided if biomarkers are developed or if combined with other agents
Summary: phase III Ramicirumab and phase II Famitinib trials in mCRC ≒ Ramicirumab added to FOLFIRI improves OS in second line for mCRC after progression on FOLFOX plus bevacizumab ≒ Famitinib does not improve OS in mCRC vs placebo after 2 failed prior regimens but does prolong PFS ≒ Need to incorporate biomarkers in trial designs to make more sense of outcomes; are drugs hitting targets/are targets present? ≒ Ramicirumab is comparable in 2nd line to other approved options ≒ Famitinib is not better in 3rd line than approved regimens ≒ Randomized comparisons or combination regimens may or may not in the future show improved or better outcomes; ? Pushing doses Presented by: Wafik El-Deiry, MD, PhD, FACP
Presented by: Wafik El-Deiry, MD, PhD, FACP From Wehland et al., Int J Mol Sci, 2013 Possible biomarkers in CRC include Serum LDH, IL-8, Angiopoietin-2, CECs Others include VEGF plasma levels, sVEGFR2, VCAM-1 & E-selectin, sKIT, HTN, tumor expression of sensitivity or resistance markers There are prognostic biomarkers to consider evaluating:
Presented by: Wafik El-Deiry, MD, PhD, FACP Clarke & Hurwitz, Exp Opin Biol Ther, 2013 The landscape of anti- angiogenic targets would appear to have more opportunities for target exploitation as well as testing of novel sequences and combinations Comment

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GI ASCO single slide per page 1-17-15

  • 1. New anti-angiogenic therapy in mCRC: FOLFIRI +/- Ramucirumab in 2nd line after FOLFOX + Bevacizumab (phase III: RAISE study) or single agent Famitinib in 3rd line (phase II randomized with placebo) Wafik El-Deiry, MD, PhD, FACP Deputy Director for Translational Research Co-Leader, Molecular Therapeutics Program Fox Chase Cancer Center January 17, 2015 Oral Abstract Session: Cancers of the Colon, Rectum, and Anus
  • 2. Learning Objectives ≒ Understand current use of anti-angiogenic therapy in mCRC ≒ Understand different anti-angiogenic therapeutic targets and agents in mCRC ≒ Explain and critique the RAISE phase III trial of Ramicirumab + FOLFIRI used in second line for mCRC ≒ Explain and critique the randomized phase II single agent Famitinib trial in 3rd line therapy of mCRC Presented by: Wafik El-Deiry, MD, PhD, FACP
  • 3. Outline of Presentation ≒ Review angiogenesis as a therapeutic target ≒ Describe approved agents and agents under investigation ≒ Critically assess the Ramicirumab and Famitinib clinical trials in mCRC Presented by: Wafik El-Deiry, MD, PhD, FACP
  • 4. Angiogenesis Presented by: Wafik El-Deiry, MD, PhD, FACP Clinical Observations in 1960s 2004 2001- 2015 Effectively translated in last two decades 1980s: VEGF
  • 5. By 2010, many inhibitors tried in mCRC, most failed Presented by: Wafik El-Deiry, MD, PhD, FACP By 2010, there was no progress in angiogenesis inhibition beyond bevacizumab Regorafenib, VEGF-trap, Tie2, bFGF, angiopoietin inhibitors were being tested
  • 6. Angiogenesis beyond VEGF in mCRC Presented by: Wafik El-Deiry, MD, PhD, FACP Phase III CORRECT Trial in mCRC Phase III VELOUR Trial in mCRC Regorafenib & Aflibercept approved in 2012 Targets include VEGFRs, Ang-2, PDGFR-硫, FGFR
  • 7. Current NCCN Guidelines for mCRC Presented by: Wafik El-Deiry, MD, PhD, FACP NCCN Guidelines now include Ziv-aflibercept in 2nd line and regorafenib in 3rd line regimens
  • 8. Presented by: Wafik El-Deiry, MD, PhD, FACP
  • 9. Ramicurimab Presented by: Wafik El-Deiry, MD, PhD, FACP ≒ Ramicurimab is a fully humanized angiogenesis inhibitory antibody that targets VEGFR2 and prevents binding of VEGF ≒ Approved by FDA in April 2014 to treat gastric or GE junction cancer after it improved OS ≒ Known side-effects include diarrhea and hypertension VEGFR2
  • 10. Presented by: Wafik El-Deiry, MD, PhD, FACP Ramicirumab was approved by the FDA in combination with docetaxel for NSCLC following progression on platinum- based therapy on December 12, 2014
  • 11. Phase II study of Ramicurimab plus FOLFOX as frontline therapy in mCRC Presented by: Wafik El-Deiry, MD, PhD, FACP
  • 12. RAISE Study of Ramicurimab Presented by: Wafik El-Deiry, MD, PhD, FACP ≒ A randomized, double- blind, multicenter phase III of FOLFIRI + Ramicurimab or placebo in patients with mCRC progression during or following FOLFOX + Bevacizumab N= 536 N= 536 1072 patients
  • 13. RAISE: Ramicurimab + FOLFIRI in 2nd line mCRC after FOLFOX + Bevacizumab improved OS Presented by: Wafik El-Deiry, MD, PhD, FACP ≒ Lots of patients with WT KRAS (~50%) were eligible in both arms ≒ The two arms were well-matched at baseline ≒ Addition of Ramicurimab to FOLFIRI prolonged median overall survival by 13.3 months versus 11.7 months for FOLFIRI alone P = 0.0219 ≒ The most common grade 3/4 adverse events with ramicurimab were neutropenia, fatigue, hypertension and diarrhea Time (months) 0 3 6 9 12 15 18 21 24 27 30 33 36 39 42 OverallSurvival 0.0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1.0 Ramicurimab increased OS when added to FOLFIRI in 2nd line therapy of mCRC to 13.3 mo vs 11.7 mo for FOLFIRI alone Ramicurimab also increased PFS when added to FOLFIRI in 2nd line therapy of mCRC to 5.7 mo vs 4.5 mo for FOLFIRI alone (P = 0.0005) P = 0.0219 536 patients in each arm
  • 14. 3 Studies RAISE, TML, & VELOUR looked at anti-angiogenic therapy in the second line after first line CT + Bev Presented by: Wafik El-Deiry, MD, PhD, FACP FOLFOX + Bev ! FOLFIRI -/+ Ramicurimab FOLFOX or + Bev ! FOLFOX or -/+ Bev FOLFIRI FOLFIRI FOLFOX -/+ Bev ! FOLFIRI -/+ ziv-Aflibercept RAISE: TML: VELOUR: First Line Second Line
  • 15. TML: Bevacizumab + FOLFIRI in 2nd line mCRC after FOLFOX or FOLFIRI + Bevacizumab improved OS Presented by: Wafik El-Deiry, MD, PhD, FACP ≒ Similar design as RAISE ≒ Similar outcomes for PFS/OS extension FOLFIRI FOLFIRI + Ramicurimab FOLFIRI/ FOLFOX FOLFIRI + bevacizumab PFS 4.5 5.7 4.1 5.7 OS 11.7 13.3 9.8 11.2 RAISE arms TML arms PFS and OS: median survival in months Not exactly the same: In TML patients had either FOLFOX or FOLFIRI in first line + bevacizumab and randomized to FOLFOX or FOLFIRI -/+ bevacizumab beyond progression TML TML PFSTML OS
  • 16. VELOUR: Aflibercept + FOLFIRI in 2nd line mCRC after FOLFOX + Bevacizumab improved OS Presented by: Wafik El-Deiry, MD, PhD, FACP ≒ Similar design as RAISE ≒ Similar outcomes for OS extension FOLFIRI FOLFIRI + Ramicurimab FOLFIRI FOLFIRI + Aflibercept PFS 4.5 5.7 4.67 6.90 OS 11.7 13.3 12.06 13.5 RAISE arms VELOUR arms PFS and OS: median survival in months Not exactly the same: In VELOUR most patients had no prior Bevacizumab which may explain slightly lower PFS numbers in RAISE although it didnt seem to impact the OS data
  • 17. VELOUR: Aflibercept + FOLFIRI in 2nd line mCRC after FOLFOX + Bevacizumab improved OS Presented by: Wafik El-Deiry, MD, PhD, FACP In VELOUR less than 1/3 of patients received prior Bevacizumab whereas in RAISE all patients received at least 2 doses of Bevacizumab
  • 18. RAISE vs TML vs VELOUR summary of outcomes Presented by: Wafik El-Deiry, MD, PhD, FACP RAISE: TML: VELOUR: PFS -/+ OS -/+ 4.5/ 5.7 m 11.7/ 13.3 m 4.1/ 5.7 m 9.8/ 11.2 m 4.7/ 6.9 m 12.1/ 13.5 m ≒ Outcomes appear similar although designs not exactly the same ≒ Need randomized comparisons ≒ ? If there may be benefit from ziv or Ram beyond Bev & Ram or ziv (3rd line) ≒ ? If it may be worth trying to combine anti-angiogenics ≒ Was too toxic in RCC but is this universally true with all agent combinations? FOLFOX + Bev ! FOLFIRI -/+ Ramicurimab FOLFOX or + Bev ! FOLFOX or -/+ Bev FOLFIRI FOLFIRI FOLFOX -/+ Bev ! FOLFIRI -/+ ziv-Aflibercept First Line Second Line
  • 19. RAISE Comments: Ramicurimab + FOLFIRI in 2nd line mCRC after FOLFOX + Bevacizumab Presented by: Wafik El-Deiry, MD, PhD, FACP ≒ Ramicurimab is effective to prolong OS in the second line therapy when combined with FOLFIRI after progression on FOLFOX plus Bevacizumab ≒ The combination was well-tolerated (with some added toxicities in the combo) ≒ Recap of some possible future directions: ≒ Ramicurimab + FOLFIRI vs Bev + FOLFIRI in 2nd line after FOLFOX + Bev ≒ Ramicurimab + FOLFIRI in patients with prior FOLFOX without Bev ≒ Ramicurimab + FOLFIRI vs anti-EGFR + FOLFIRI in 2nd line in WT KRAS population ≒ Single agent Ram in patients who cant tolerate chemo ≒ Ram or Ram + cape maintenance ≒ Ram + FOLFIRI vs Aflibercept + FOLFIRI in 2nd line with prior FOLFOX or FOLFOX + Bev ≒ Need biomarkers to predict best responders vs those less likely to benefit ≒ In 2015 need to assess and compare financial toxicities
  • 20. Ramicurimab in gastric cancerposter at 2015 GI ASCO Presented by: Wafik El-Deiry, MD, PhD, FACP Potential to push dose of Ramicirumab to improve outcomes
  • 21. A randomized, double-blind, parallel-group, placebo controlled, multi-center, phase II clinical study of Famitinib in the treatment of advanced metastatic colorectal cancer Rui-hua Xu*, Lin Shen*, Ke-ming Wang, Gang Wu, Chun-mei Shi, Ke-feng Ding, Li-zhu Lin, Jin-wan Wang, Jian-ping Xiong, Chang-ping Wu, Jin Li, Yun-peng Liu, Dong Wang, Yi Ba, Jue-ping Feng, Yu-xian Bai, Jing-Wang Bi, Li-wen MA, Jian Lei and Hao Yu *Co-Leading Principle Investigator Abstract No.513 Presented by: Rui-hua Xu
  • 22. Famitinib targets Presented by: Wafik El-Deiry, MD, PhD, FACP KDR/VEGFR2 cKit PDGFR Anti-angiogenesis
  • 23. Famitinib targets Presented by: Wafik El-Deiry, MD, PhD, FACP
  • 24. Famitinib had efficacy in NPC phase II trial Presented by: Wafik El-Deiry, MD, PhD, FACP
  • 25. Famitinib in mCRC Presented by: Wafik El-Deiry, MD, PhD, FACP ≒ 154 patients 2:1 randomization; groups well matched ≒ 1.3 mo prolongation of FPS (P = 0.0053) & 59.8% DCR ≒ Breakdown of prior therapies unclear; FOLFOX, FOLFIRI, cetuximab and bevacizumab are available in China ≒ No difference in OS noted ≒ AEs included proteinuria, neutropenia, HTN, thrombocytopenia, H/F syndrome and diarrhea PFS Data:
  • 26. Regorafenib in mCRC Presented by: Wafik El-Deiry, MD, PhD, FACP ≒ 1052 patients 2:1 randomization; groups well matched ≒ 1.9 mo prolongation of FPS and 6.4 mo (Regoraf) vs 5.0 mo (placebo) OS OS/PFS Data: ≒ Subgroup analyses supported impact of Regorafenib on OS including KRAS mutant mCRC ≒ Lack of demonstrated effect on OS by Famitinib may be aided if biomarkers are developed or if combined with other agents
  • 27. Summary: phase III Ramicirumab and phase II Famitinib trials in mCRC ≒ Ramicirumab added to FOLFIRI improves OS in second line for mCRC after progression on FOLFOX plus bevacizumab ≒ Famitinib does not improve OS in mCRC vs placebo after 2 failed prior regimens but does prolong PFS ≒ Need to incorporate biomarkers in trial designs to make more sense of outcomes; are drugs hitting targets/are targets present? ≒ Ramicirumab is comparable in 2nd line to other approved options ≒ Famitinib is not better in 3rd line than approved regimens ≒ Randomized comparisons or combination regimens may or may not in the future show improved or better outcomes; ? Pushing doses Presented by: Wafik El-Deiry, MD, PhD, FACP
  • 28. Presented by: Wafik El-Deiry, MD, PhD, FACP From Wehland et al., Int J Mol Sci, 2013 Possible biomarkers in CRC include Serum LDH, IL-8, Angiopoietin-2, CECs Others include VEGF plasma levels, sVEGFR2, VCAM-1 & E-selectin, sKIT, HTN, tumor expression of sensitivity or resistance markers There are prognostic biomarkers to consider evaluating:
  • 29. Presented by: Wafik El-Deiry, MD, PhD, FACP Clarke & Hurwitz, Exp Opin Biol Ther, 2013 The landscape of anti- angiogenic targets would appear to have more opportunities for target exploitation as well as testing of novel sequences and combinations Comment