COLORECTAL CANCER. Bert H. O Neil, MD Jackie and Joseph Cusick Professor of Oncology Director, GI Malignancies and Phase I Program

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1 COLORECTAL CANCER Bert H. O Neil, MD Jackie and Joseph Cusick Professor of Oncology Director, GI Malignancies and Phase I Program

2 Rectal Cancer Adjuvant therapy No single study specific to rectal cancer has proven that adjuvant chemotherapy is beneficial Cochrane meta-analysis suggests benefit of FU-based Rx EORTC study (FU/LV alone) long-term follow-up negative for OS Role of oxaliplatin has remained unclear Clearly not beneficial as radiosensitizer Most have extrapolated from the stage III colon cancer studies to give adjuvant FOLFOX 3 randomized trials presented at ASCO 2014

3 Preoperative chemoradiotherapy and postoperative chemotherapy with 5-FU and oxaliplatin versus 5-FU alone in locally advanced rectal cancer<br /><br />Results of the CAO/ARO/AIO-04 <br />randomized phase III trial Presented By Claus Rodel at 2014 ASCO Annual Meeting

4 Slide 5 Presented By Claus Rodel at 2014 ASCO Annual Meeting

5 Slide 6 Presented By Claus Rodel at 2014 ASCO Annual Meeting

6 Slide 9 Presented By Claus Rodel at 2014 ASCO Annual Meeting

7 Slide 18 Presented By Claus Rodel at 2014 ASCO Annual Meeting

8 Slide 22 Presented By Claus Rodel at 2014 ASCO Annual Meeting

9 <br /><br /><br />Preoperative chemoradiotherapy and postoperative chemotherapy with capecitabine + oxaliplatin vs. capecitabine alone in locally advanced rectal cancer: Early results of the PETACC 6 trial<br /> Presented By Hans-Joachim Schmoll at 2014 ASCO Annual Meeting

10 Slide 5 Presented By Hans-Joachim Schmoll at 2014 ASCO Annual Meeting

11 CONSORT II Presented By Hans-Joachim Schmoll at 2014 ASCO Annual Meeting

12 Disease-free survival: primary analysis (ITT)<br /> follow up 31 months ( years) Presented By Hans-Joachim Schmoll at 2014 ASCO Annual Meeting

13 ADORE Study Conducted in Asia Randomized 321 patients post-operatively to FL (Mayo) vs. FOLFOX All patients had preoperative CRT EXCLUDED patients with pcr or pyt1-2n0 disease

14 DFS Plots Presented By Carmen Allegra at 2014 ASCO Annual Meeting

15 Conclusions-Rectal Hints but not proof that oxaliplatin improves outcome when given out back after CRT Surgery ADORE showed largest benefit, but used potentially inferior control arm (Mayo FU/LV) PETACC-6 showed least benefit, but suffered imbalance of completion of therapy in Ox arm Should you change your practice if you give oxali? May want to consider risk stratification- withhold for pateints with lower-risk disease (pcr, pyt1-2n0) HOWEVER.

16 Effect of adjuvant chemotherapy in pts with good and poor response to pre-op treatment DFS JCO October 1, 2007 vol. 25 no

17 Conclusions-Rectal Hints but not proof that oxaliplatin improves outcome when given out back after CRT Surgery ADORE showed largest benefit, but used potentially inferior control arm (Mayo FU/LV) PETACC-6 showed least benefit, but suffered from issues of lack of completion of therapy Should you change your practice if you give oxali? May want to consider risk stratification- withhold for pateints with lower-risk disease (pcr, pyt1-2n0) HOWEVER. My own practice will be to continue to give oxaliplatin for cn+ disease until further follow-up from the trials presented

18 Metastatic CRC Several studies have suggested a substantial OS and RR benefit when anti-egfr antibodies are added to frontline chemotherapy in KRAS wt pts CRYSTAL (cetuximab)- 4 mos overall survival Δ PRIME (panitumumab)- 4.4 mos OS Δ FIRE3 (ASCO 2013) and PEAK were first large head to head study of bev vs. cetux or panitumumab w/chemo in 1 st line Trial Comparative Regimens PFS, Mos OS, Mos PEAK [1] (N = 285) FIRE-3 [2] (N = 592) mfolfox6/pmab vs mfolfox6/bev 10.9 vs 10.1 NR vs 25.4 FOLFIRI/Cetux vs FOLFIRI/Bev 10.0 vs vs 25.0*

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20 <br />CALGB/SWOG 80405: Phase III trial of FOLFIRI or FOLFOX with Bevacizumab or Cetuximab for patients w/ KRAS wild type untreated metastatic adenocarcinoma of the colon or rectum <br /> Presented By Alan Venook at 2014 ASCO Annual Meeting

21 CALGB/SWOG 80405: <br /> FINAL DESIGN Presented By Alan Venook at 2014 ASCO Annual Meeting

22 CALGB/SWOG 80405: Eligibility Criteria Presented By Alan Venook at 2014 ASCO Annual Meeting

23 CALGB/SWOG 80405: Progression-Free Survival<br />(Investigator Determined) Presented By Alan Venook at 2014 ASCO Annual Meeting

24 CALGB/SWOG 80405: Overall Survival <br /> Presented By Alan Venook at 2014 ASCO Annual Meeting

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26 CALGB/SWOG 80405: Overall Survival<br />FOLFOX Treated Presented By Alan Venook at 2014 ASCO Annual Meeting

27 CALGB/SWOG 80405: Overall Survival<br />FOLFIRI Treated Presented By Alan Venook at 2014 ASCO Annual Meeting

28 Patients Rendered Disease-Free<br />Overall Survival Presented By Alan Venook at 2014 ASCO Annual Meeting

29 Conclusions OS for CRC has improved substantially in last decade Starting with BEV vs. CETUX appears to produce equivalent (good) outcome for KRAS wt patients FOLFOX is a reasonable backbone to use with cetuximab (or panitumumab) Patients who go to surgery have remarkably good outcome Await data on exapanded KRAS analysis- will cetux prove superior if all KRAS/NRAS mutant patients excluded? In practice consider expanded testing now