ASCO GI 2014 Update: Personalized Medicine in CRC

Colon Cancer Alliance/Fight Colorectal Cancer Webinar

February 19, 2014

Allyson J. Ocean, M.D. Associate Professor of Clinical Medicine

Weill Cornell Medical College

ASCO GI 2014 Update

Melissa Bjorklund Randy Henniger Kim Ryan

Allyson Ocean, M.D.

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Fourth most common cancer diagnosis in US[1]

Estimated 142,820 new cases in 2013; 1:1 male:female ratio[2]

Second leading cause of cancer deaths in 2013 (estimated 50,830 deaths)[1]

Steady decrease in age-adjusted incidence rates of distal colon, proximal colon, and rectal cancers in 1976-2005[4]

CRC: Epidemiology in 2013

1. American Cancer Society. Cancer facts & figures. 2013. 2. Siegel R, et al. CA Cancer J Clin. 2012;62:10-29. 3. SEER. Stat fact sheets: colon and rectum. 4. Cheng L, et al. Am Clin Oncol. 2011;34:573-580.

Death Rates in 2008, per 100,000[3], %

Male Female

All races 20.2 14.1

White 19.5 13.6

Black 29.8 19.8

Asian/Pacific Islander 13.1 9.6

American Indian/ Alaska Native

18.8 14.6

Hispanic 15.3 10.2

Incidence rising SHARPLY in younger adults in U.S.

Researchers analyzed SEER data for 383,241 patients in whom CRC diagnosed between 1975 and 2010

Age-adjusted incidence of CRC fell steadily among >50

Annual percentage change in rates rose in patients aged 35-49 at diagnosis and ESPECIALLY aged 20-34

Results similar for colon and rectum

Colorectal Cancer in Young Adults

Study lead author, Dr. Christina Bailey, M.D. Anderson, ASCO GI 2014 Poster

Predictive model suggested that if observed trends persist between 2010 and 2030, incidences of colon cancer and rectal cancer will rise by 90% and 124% respectively among 20-34 yo and by 28% and 46% respectively in 35-49 yo

Why? Possible reasons: Increasing obesity rates, physical inactivity, diet high in fat and red meat

Primary care docs may be more alert for this cancer in young adults with symptoms like rectal bleeding

What does this mean for young adults?

Colorectal Cancer: Stage at Diagnosis

National Cancer Database.

Stage

0 7%

Stage I 24%

Stage II 25%

Stage III 25%

Stage IV 19%

Stage Colon Rectal

I (T1-T2, N0, M0) Surgery only Surgery only

II (T3-T4, N0, M0) Surgery ±

chemotherapy

Chemoradiation surgery

chemotherapy

OR

Surgery chemoradiation

+ chemotherapy

III (Tany, N+, M0) Surgery

chemotherapy

IV (Tany, Nany, M1) Chemotherapy ±

surgery

Chemotherapy ±

surgery

Colorectal Cancer: Standard Therapy Algorithm

NCCN. Clinical practice guidelines in oncology: colon cancer. v.1.2014.

Early Stage Disease

Through an analysis of physician recommendations and patient treatment preferences before and after receiving the Oncotype DX colon cancer test results, this study demonstrated that the test greatly increased concordance between physician and patient treatment choice (from 66 percent to 96 percent).

Recurrence Score® result influenced a majority of patients' treatment decisions (85 percent) and physicians' treatment recommendations (69 percent), and it increased physicians' confidence in their own recommendations (84 percent).

Patients' anxiety was also significantly reduced, which may improve adherence to their treatment plan and ultimately lead to better health outcomes.

Oncotype DX News

The review of four validation studies of the Oncotype DX colon cancer test (3,315 patients) with early stage colon cancer, consistently demonstrated a significant association (p < 0.05) between the test results and recurrence risk and cancer-specific survival.

Three decision impact studies with a total of 502 patients showed that the test changed treatment recommendations in 29 to 45 percent of stage II colon cancer cases, leading to a net reduction in adjuvant chemotherapy use.

Oncotype DX

Phase III randomized trial in neoadjuvant rectal cancer- mature results presented

Combining preoperative radiation with oral capecitabine (Xeloda) was equally as effective as our old standby, infusional 5-FU chemo, in terms of local-regional recurrence rates

Largest clinical trial showing no difference in clinical benefit

Provides for better quality of life for patients

Not tied down to getting a catheter treatment and able to take an oral agent

Adding oxaliplatin to either treatment did not improve clinical response rates

Final Results of NSABP R-04

Allegra et. al ASCO GI 2014 Abstract 390

Spanish trial for pre-operative (neoadjuvant) treatment of rectal cancer Tips the balance in favor of induction chemotherapy followed by

chemoradiotherapy and then surgery vs. the standard approach of chemoradiotherapy followed by surgery and then adjuvant chemotherapy in patients with locally advanced rectal cancer

Pathologic CR rates, locoregional recurrence, distant recurrence, disease-free survival, and overall survival all proved similar between the two approaches out to 5 years

Less acute toxicity and better compliance to chemotherapy component of the regimens was identified with the induction approach vs. the standard approach

Need large phase III randomized trials to definitively find best approach

Phase III GCR-3 Trial

ASCO GI 2014 Abstract 383

Metastatic Disease

Personalizing Treatment in mCRC: Considerations

Extent of disease

Intent of treatment (palliative vs potentially curative)

Performance score

Age

Comorbid illnesses

Previous adjuvant therapy within 1 yr

Molecular markers

Organ function: hepatic and renal

Risks for toxicity: active CAD/CVD, proteinuria, active bleeding, nonhealed wound, allergy to mAb, neuropathy, IBD, ILD, Gilberts

Convenience

Cost/resources

Patient preferences and goals

Phase III CAIRO3 trial

Data provides guidance about how big a treatment holiday to give patients following induction therapy

Maintenance treatment with Xeloda and Avastin after 6 cycles of CAPOX-B (Xeloda, Oxaliplatin, Avastin) significantly prolonged time to disease progression

Overall survival benefit for maintenance treatment in certain patient groups (synchronous disease with resection of primary tumor and in patients with complete or partial response as best response on induction treatment)

Maintenance Capecitabine/Bevacizumab Delays Disease Progression

Koopman et. al ASCO GI 2014 LBA

Studies focused on leveraging prognostic and predictive information

More extensive genetic testing for RAS gene mutations beyond routine analysis of K-RAS exon 2 may soon become a new standard of care to pinpoint which patients stand to benefit from anti-EGFR therapy

K-RAS mutations present in approximately 40-50% of mCRC tumors

If K-RAS mutation present- can’t use Erbitux or Vectibix

Improving outcome for CRC patients

Peeters et. al, ASCO GI 2014 Abstract LBA387

Addition of DEBIRI to 1st line FOLFOX in unresectable liver-limited metastatic CRC enables downstaging and subsequent resection in more than 1/3 of patients

Placement of the beads in the hepatic artery did not increase chemotherapy toxicity or compromise overall treatment delivery

This phase II trial was conducted in 70 patients with CRC with liver metastases

Irinotecan beads administered to hepatic artery during off week of chemotherapy; outpatient procedure

Key is finding the patients most appropriate for this therapy

Irinotecan drug-eluting beads (DEBIRI)

Martin et. al, ASCO GI 2014 Abstract 174

Personalized medicine: What does it mean for YOU?

Ask about the genetics of your tumor

Ask about the K-RAS mutations of your tumor

Ask about genome sequencing of your tumor

Take advantage of educational websites

CCA, Fight CRC, Michael’s Mission

Connect with other patients and survivors

Links to novel treatments

Thoughts/Conclusions/Questions