Oncology Update July '13

Saint Francis Cancer Treatment Center

Oncology Update03I S S U E

J U L Y2 0 1 3

Dr. Melhem Jabbour • Dr. M. Sitki Copur • Dr. Ryan Ramaekers

GRAND ISLAND & HASTINGS, NEBRASKA

B r i n g i n g t h e b e s t c a n c e r c a r e t o y o u r c o m m u n i t i e s

2010 Outstanding Achievement Award

in this issue• Prophylactic platelet transfusion in hematological

malignancy with severe thrombocytopenia

• Bevacizumab in recurrent and metastatic cervical cancer

• Sorafenib in radioactive iodine-refractory differentiated thyroid cancer

• Navigation services at Saint Francis

• Long-term effects of continuing adjuvant tamoxifen to 10 years

Clark to Join Cancer Treatment CenterSaint Francis Cancer Treatment Center would like to welcome a new radiation oncologist, Dr. Doug Clark. Dr. Clark hails from Longview, WA, and grew up in the Puget Sound region. He completed his undergraduate studies at Johns Hopkins University, majoring in Biophysics and Art History, and earned his medical degree from the University of Washington.

After graduating, Dr. Clark completed a transitional internship at Deaconess Medical Center in Spokane, WA, along with a residency in radiation oncology at the University of Rochester in Rochester, NY. He has also worked at Fitzsimons Army Medical center, as well as in Ohio and Oklahoma. Dr. Clark most recently practiced radiation oncology at Mercy Medical Center in Williston, ND.

Dr. Clark married his classmate, Shu-Ming Wang, M.D., the day after their medical school graduation. She is a family practitioner and is currently completing an Executive Masters in Health Administration at Missouri State University. Together, they enjoy food, wine and entertaining. They also have a strong sense of adventure and love to travel the world. Their other hobbies include art, music and creative writing. They have no children.

Dr. Clark will begin seeing patients July 29. To refer a patient or speak with Dr. Clark, please contact the Cancer Treatment Center at (308) 398-5450.

Doug Clark, M.D.

Recent Hematology/Oncology Drug Approvals by FDA:• FDA approved radium Ra 223 dichloride (Xofigo

Injection, Bayer HealthCare Pharmaceuticals Inc.) for the treatment of patients with castration-resistant prostate cancer, symptomatic bone metastases and no known visceral metastatic disease. Xofigo is an alpha-particle emitting radio therapeutic drug which mimics calcium and forms complexes with hydroxyapatite at areas of increased bone turnover, such as bone metastases. May 15, 2013.

• FDA approved erlotinib (Tarceva, Astellas Pharma Inc.) for the first-line treatment of metastatic non-small cell lung cancer (NSCLC) patients whose tumors have epidermal growth factor receptor (EGFR) exon 19 deletions or exon 21 (L858R)

substitution mutations. This indication for erlotinib is being approved concurrently with the cobas EGFR Mutation Test, a companion diagnostic test for patient selection. May 14, 2013.

• FDA approved two oral oncology drugs; BRAF-inhibitor Tafinlar® (dabrafenib) capsules and the first MEK-inhibitor Mekinist™ (trametinib) tablets, as single-agent therapies. Both oral drugs are approved for unresectable or metastatic melanoma with BRAF V600E mutation. May 31, 2013.

• The Administration approved lenalidomide (Revlimid) for the treatment of patients with mantle cell lymphoma whose disease has relapsed or progressed after two prior therapies, one of which included bortezomib (Velcade). June 5,2013.

Prophylactic platelet transfusion is necessary in patients with hematological malignancies and severe thrombocytopenia, A Randomized Controlled, Non-Inferiority Trial (TOPPS trial)

The effectiveness of prophylactic platelets to prevent bleeding in patients with hematological malignancies remains unclear. A randomized, open-label, non-inferiority trial assessed whether a policy of not giving prophylactic platelet transfusions was as effective and safe.

The primary outcome was proportion of patients with a clinically significant bleed defined as ≥WHO Grade 2 up to 30 days from randomization. Adult patients were eligible if they had a hematological malignancy and receiving chemotherapy or stem cell transplant with an expected duration of thrombocytopenia for at least 5 days. Patients were randomized to receive either prophylactic platelet transfusion if platelet count was <10x109/L, or no prophylaxis platelet transfusion. Allocated treatment policy applied for 30 days from randomization, irrespective of in- or out-patient status. In both arms platelet transfusions were given therapeutically (documented signs or

symptoms of bleeding) or prior to invasive procedures or at physician discretion. Analysis was by intention to treat. A WHO grade 2-4 bleed occurred in 151/300 patients (50%) in the no-prophylaxis group compared to 128/298 (43%) in the prophylaxis group (adjusted difference in proportions 8.4%, 90% CI 1.7 to 15.2%: p-value for non-inferiority 0.06).

This study therefore did not prove its main aim, that a no-prophylaxis policy is non-inferior to prophylaxis. The time to the first grade 2-4 bleed was significantly shorter in the no-prophylaxis group. Patients in the no-prophylaxis group had more days with a WHO grade 2 or above bleed, and a shorter time to first bleed. The results of this study support the need for the continued use of prophylaxis with platelet transfusion and show the benefit of such prophylaxis in reducing bleeding, as compared with no prophylaxis. Reference: Simon J. Stanworth, D.Phil, Lise J. Estcourt, et al. A No-Prophylaxis Platelet-Transfusion Strategy for Hematologic Cancers N Engl J Med 368;19,May 9, 2013

Potentially PracticeChanging Data

Incorporation of bevacizumab in the treatment of recurrent and metastatic cervical cancer; A Phase III randomized trial of the Gynecologic Oncology Group (GOG)

According to NCI estimates, 12,000 women in the United States were diagnosed with cervical cancer in 2012, and 4000 died from it. The incidence is much higher is underdeveloped countries, where there is no regular screening, and worldwide cervical cancer is the third most common cancer in women with an estimated 500,000 new cases and 250,000 deaths. GOG-240 trial involved 452 patients with pre-treated metastatic, recurrent, or persistent cervical cancer enrolled between 2009 and 2012 in the United States and Spain. Four-arm trial randomly assigned patients to receive either topotecan or cisplatin in combination with paclitaxel, and also to have bevacizumab added or not added to the chemotherapy. Women with metastatic or recurrent cervical cancer had significantly prolonged survival when bevacizumab was added to chemotherapy. The median overall survival was 17 months for women receiving the combination, compared with 13.3 months for women receiving chemotherapy alone (hazard ratio, 0.71; P = .0035). This is the first time that a targeted agent has shown an improvement in survival in cervical cancer. The results are practice-changing, and the manufacturer has filed for approval of advanced cervical cancer as a new indication for bevacizumab. The trial was conducted by the Gynecologic Oncology Group and was funded by the National Cancer Institute (NCI).

Reference: Tewari KS et al. Incorporation of bevacizumab in the treatment of recurrent and metastatic cervical cancer; A Phase III randomized trial of the Gynecologic Oncology Group. J Clin Oncol 2013;31:6s. abstract.asco.org.


Navigation Services at Saint Francis Cancer Treatment CenterReceiving a cancer diagnosis is a very confusing and frightening time for patients. They begin seeing new physicians and hearing terms that are unfamiliar – all while trying to absorb a lot of life-changing information.

The navigation team at Saint Francis Cancer Treatment Center is here to help make that transition easier for breast and colorectal cancer patients. Our navigators are available to assist your patients as soon as they receive a cancer diagnosis. The goal is to bring the navigator on board as early as possible in the treatment so that they can assist the patient in coordinating appointments and providing basic education on their diagnosis.

It is important to understand that both you and your patient will have full autonomy in deciding where patient care is received. The navigation program has no intention of changing practice referral patterns or influencing the patient’s decision on the selection of their breast or colorectal care providers. The navigator is simply there to coordinate care, provide support and schedule appointments with whichever providers are requested.

If the patient chooses to receive their care in Grand Island, their case will be discussed at our biweekly multidisciplinary tumor conference. The navigator will also be able to accompany the patient to the initial meetings with the surgeon, radiation oncologist, and medical oncologist. Even if the patient chooses to have her care outside of Grand Island, our navigator will still provide the patient with education and will coordinate all of the appointments.

Your role is very simple. If you have a patient who has a new diagnosis of breast, colon or rectal cancer, all you need to do is contact the Saint Francis Cancer Treatment Center at (308) 398-5450. You will be directed to the appropriate navigator, who will then contact the patient and coordinate appointments with a medical oncologist and a surgeon, normally within a week. The patient will receive basic education on what to expect along their cancer journey, as well as a number of resources to help with their education.

Sorafenib in locally advanced or metastatic patients with radioactive iodine-refractory differentiated thyroid cancer: The phase III DECISION trial Conventional cytotoxic chemotherapy has not been effective in the management of differentiated thyroid cancers in spite of significant toxicities. Sorafenib blocks the enzyme RAF kinase, a critical component of the RAF/MEK/ERK signaling pathway controlling cell division and proliferation. It also inhibits the VEGFR-2/PDGFR-beta signaling cascade. Sorafenib is currently approved to treat hepatocellular carcinoma and advanced renal cell carcinoma. Results of a phase 3 clinical trial, DECISION, in 417 patients with progressive radioactive iodine -refractory differentiated thyroid cancer showed a significant improvement in median progression-free survival to 10.8 months in the sorafenib group compared to 5.8 months in the placebo arm. Within the cohort, tumor histology was 57% papillary, 25% follicular, and 10% poorly differentiated, and the vast majority (96%) of patients had metastatic disease. The most common target lesions were lung (71%), lymph node (40%), and bone (14%). The primary endpoint of the study was progression-free survival, which was assessed every 8 weeks. Secondary endpoints included overall survival, response rate (complete and partial response), and drug safety. The authors note that their primary endpoint of progression-free survival was met (hazard ratio, 0.58; P < .0001). The median overall survival has not yet been reached in either study arm, and 70% of placebo patients have started open-label sorafenib. All reported responses were partial — 12.2% in the sorafenib group vs 0.5% for placebo (P < .0001). Stable disease ≥ 6 months was 42% and 33%, respectively. Tolerability was consistent with the known sorafenib safety profile, the authors note. The most common any-grade treatment-emergent adverse events in the sorafenib arm included hand–foot skin reaction, diarrhea, alopecia, rash/desquamation, fatigue, weight loss, and hypertension.

Reference: Brose MS et al. Sorafenib in locally advanced or metastatic patients with radioactive iodine-refractory differentiated thyroid cancer: The phase III DECISION trial. J Clin Oncol 2013;31:6s. abstract.asco.org.


A Study of PD-0332991 + Letrozole vs Letrozole for First Line Treatment of Postmenopausal Women With ER+/HER2- Advanced Breast Cancer

This study is designed to compare the clinical benefit following treatment with letrozole in combination with PD-0332991 versus letrozole in combination with placebo in postmenopausal women with ER(+)/HER2(-) advanced breast cancer who have not received prior systemic anti-cancer therapy for their advanced/metastatic disease. PD 0332991 is an oral cyclin-D Kinase inhibitor. Preclinical studies identified breast cancer tumor characteristics sensitive to PD-0332991, which includes Luminal ER-positive subtype, elevated cyclin D1 and Rb expression, and decreased p16 expression. In vitro Phase I study of PD 0332991 plus letrozole determined the recommended phase II dosing in combination with letrozole as 125 mg/day of PD 0332991 for 3 weeks of a 4 week cycle. This study was activated at Saint Francis on June 6. We currently have two patients enrolled and a third patient in the enrollment process.

The research staff at the Cancer Treatment Center receives protocol training from the Pfizer/Trio site monitor prior to activation of PD-0332991 on June 6.

Clinical Trial News:

New Breast Cancer Clinical Trial at Saint Francis Cancer Treatment Center:

aTTom: Long-term effects of continuing adjuvant tamoxifen to 10 years versus stopping at 5 years in 6953 women with early breast cancer


Daily tamoxifen for 5 years is the current worldwide standard for the treatment of hormone-receptor-positive breast cancer. However, it has not been clear whether continuing beyond 5 years produces further benefit. Ten years of adjuvant treatment with tamoxifen was better than the standard 5 years in terms of reducing the risk for breast cancer recurrence and disease-specific death, according to results from ATLAS trial which was covered in April issue of our newsletter. This second trial, known as aTTom (adjuvant Tamoxifen Treatment Offers More?), was conducted in the United Kingdom. From 1991 to 2005, aTTom investigators randomly assigned 6953 women who had been using tamoxifen for 5 years to either continue treatment with tamoxifen for another 5 years or to stop immediately. The women were either ER-positive (n = 2755) or untested (n = 4198; estimated to be 80% ER-positive if status unknown). The women were contacted annually to assess treatment compliance, recurrence, hospital admissions, and death rates. About 75% of women in the 10-year group continued to take tamoxifen as directed. The additional years on tamoxifen had little effect on recurrence and mortality during the period of 5 to 9 years after diagnosis. By contrast, during the second decade after diagnosis, the women who had

been allocated to continue tamoxifen treatment had a 25% lower breast cancer mortality rate than the women who had been allocated to stop after 5 years. Non-breast-cancer mortality was little affected in the longer treatment and 5-year treatment groups (457 vs. 467 deaths; rate ratio, 0.94). The longer time on tamoxifen increased the risk for endometrial cancer, a known side effect of treatment. There were 102 vs 45 endometrial cancers in the 10-year and the 5-year treatment groups, respectively. Also, among the longer treatment group, there were 37 deaths from endometrial cancer (1.1%) compared with 20 such deaths (0.6%) in the 5-year group (absolute hazard, 0.5%; P = .02). The longer-treatment group had fewer breast cancer recurrences compared with the 5-year treatment group (28% vs 32%; P = .003). Longer treatment also reduced breast cancer mortality compared with 5 years of treatment (392 vs 443 deaths after recurrence; 21% vs 24%; P = .06). The results are “practice changing” for premenopausal women with hormone-receptor-positive breast cancer.

Reference: Gray RG et al. aTTom: Long-term effects of continuing adjuvant tamoxifen to 10 years versus stopping at 5 years in 6953 women with early breast cancer. J Clin Oncol 2013;31:6s. abstract.asco.org.

The incidence of local recurrence after conservative surgery for early breast cancer without adjuvant therapy is unacceptably high even with favorable tumors. The aim of this study was to examine the effect of adjuvant therapies in tumors with excellent prognostic features. Patients with primary invasive breast cancer <2 cm diameter, grade 1 or good prognosis special type, and node negative, treated by wide local excision with clear margins were randomized into a 2 × 2 clinical trial of factorial design with or without radiotherapy and with or without tamoxifen. Trial entry was allowed to either comparison or both. The actuarial breast cancer specific survival in 1135 randomized patients at 10 years was 96%. Analysis by intention to treat showed that local recurrence after wide local excision was reduced in patients randomized to radiotherapy (HR 0.37, CI 0.22-0.61 p < 0.001) and to tamoxifen (HR 0.33, CI 0.15 – 0.70 p < 0.004). Actuarial analysis of patients entered into the four-way randomization showed

that local recurrence after wide local excision alone was 1.9% per annum versus 0.7% with RT alone and 0.8% with tamoxifen alone. No patient randomized to both adjuvant treatments developed local recurrence. Analysis by treatment received showed local recurrence at 2.2% per year for surgery alone versus 0.8% for either adjuvant radiotherapy or tamoxifen and 0.2% for both treatments. Even in these patients with tumors of excellent prognosis, local recurrence after conservative surgery without adjuvant therapy was still very high. This was reduced to a similar extent by either radiotherapy or tamoxifen but to a greater extent by the receipt of both treatments.

Reference: Blamey RW, Bates T, Chetty U et al. Radiotherapy or tamoxifen after conserving surgery for breast cancers of excellent prognosis: British Association of Surgical Oncology (BASO) II trial, Eur J Cancer 2013;March 21. pii: S0959-8049(13)00163-9. doi: 10.1016/j.ejca.2013.02.031. [Epub ahead of print]

Radiotherapy or tamoxifen after conserving surgery for breast cancers of excellent prognosis: British Association of Surgical Oncology (BASO) II trial

Mammograms Can Measure How Breast Cancer Drug Is Working: Mammographic Density Reduction is a Prognostic Marker of Response to Adjuvant Tamoxifen Therapy in Postmenopausal Patients with Breast Cancer Study

Mammograms can be used to see how well breast cancer patients are responding to treatment with the drug tamoxifen. Mammographic Density Reduction can be utilized as a Prognostic Marker of Response to Adjuvant Tamoxifen Therapy in Postmenopausal Patients with Breast Cancer. Overall, 974 postmenopausal patients with breast cancer who had both a baseline and a follow-up mammogram were evaluated in this study. On the basis of treatment information abstracted from medical records, 474 patients received tamoxifen treatment and 500 did not. Mammographic density was measured by using an automated thresholding method and expressed as absolute dense area. Change in mammographic density was calculated as percentage change from baseline. Survival analysis was performed by using delayed-entry Cox proportional hazards regression models, with death from breast cancer as the end point. Analyses were adjusted for a range of patient and tumor characteristics. Women who saw a 20 percent or more reduction in breast density during tamoxifen treatment had a 50 percent lower risk of dying from breast cancer over an average of 15 years, compared with women who had little or no change in breast tissue density during treatment.

Reference: Jingmei Li, Keith Humphreys, Louise Eriksson, Gustaf Edgren, Kamila Czene, and Per Hall. Mammographic Density Reduction Is a Prognostic Marker of Response to Adjuvant Tamoxifen Therapy in Postmenopausal Patients With Breast Cancer . J Clin Oncol 31. © 2013 by American Society of Clinical Oncology Published Ahead of Print on April 22, 2013 as 10.1200/JCO.2012.44.5015

C O N TAC T I N F O R M AT I O N Saint Francis Cancer Treatment Center2116 West Faidley AvenueGrand Island, NE 68803(308) 398-5450ht tp : / / sa in t f ranc i sg i . o rg

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Oncology Update Issue 03 July 2013

Providers:M. Sitki Copur, MD, FACP

Medical Director of OncologyMelhem Jabbour, MDRyan Ramaekers, MDRita Hays, APRN, AOCNPDeborah Nelson, APRN, AOCNPMegan Schriner, PA

Clinical Trials:Courtney Fuller, RN, OCN, CCRPMary Gulzow, CRA, CCRPRebecca Hadenfeldt, BSNJennifer Scott, BSN, OCNAlicia Wicht, CRA

Center for Translational Research Heather Benzel, RN, CCRP

Pharmacists:Angie Obermiller, PharmD

Oncology Pharmacy SupervisorJon Olsen, PharmDMark Tharnish, PharmD

Navigators:Jacque Langford, BSN, CBPN-IC

Breast Cancer Nurse NavigatorAshley Wissing, MA

Colorectal Cancer Navigator

NutritionistMaureen Hilderbrand, RD, LMNT

Genetic Counselors:Kim Brussow, CGC

Tumor RegistryLeslie Mlinar, CTRPatty Tripp, CTR, RHIT

Patient & Family Counselor:Mary Ann Kalinay, MS, LMHP

Oncology Project CoordinatorAnn Tvrdy, MSN, CRNI

Certified Tobacco Cessation Facilitator

Community Outreach CoordinatorConnie Hameloth, RN

Certified Tobacco Cessation Facilitator

Management:Max Norvell, PharmD

Director of OncologyMary Mickey, RN, OCN

Clinical Manager, Medical OncologyMarlene Hinrichs, MA (R) (T)

Clinical Manager, Radiation Therapy

Meet our team

Locations:

Saint Francis Cancer Treatment Center2116 West Faidley AvenueGrand Island, NE 68803(308) 398-5450

Saint Francis Cancer Treatment Center2nd Street & Marian RoadHastings, NE 68901(402) 461-5588

Visit us online:

SaintFrancisGI.org

Oncology Update July '13

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