New Treatment Options Lead to Steady Progress Against Ovarian Cancer

Although finding effective screening tools remains a priority, new treatment options for women with ovarian cancer, such as those outlined in the updated NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Ovarian Cancer, are vital to making steady progress against the disease according to Robert J. Morgan, MD, of City of Hope Comprehensive Cancer Center and chair of the NCCN Guidelines Panel for Ovarian Cancer. Dr. Morgan outlined significant updates to the NCCN Guidelines during a recent presentation at the NCCN 16th Annual Conference.

The NCCN Guidelines address epithelial ovarian cancer (including borderline or low malignant potential) and less common histopathologies, including malignant germ neoplasms, carcinosarcomas, and sex cord-stromal tumors.

“Regardless of the type of cancer, the NCCN Guidelines for Ovarian Cancer reflect the importance of stage and grade of disease on prognosis and treatment recommendations,” said Dr. Morgan.

The NCCN Guidelines continue to recommend that women with borderline epithelial ovarian cancer of low malignant potential be primarily surgically managed. In contrast to patients with frankly invasive ovarian carcinoma, women with borderline disease tend to be younger and are often diagnosed with stage I disease.

“The benefit of postoperative chemotherapy has not been demonstrated for patients who have no microscopically demonstrable invasive implants,” said Dr. Morgan. “Even patients with advanced-stage disease at presentation have an excellent prognosis and chemotherapy should be avoided.”

The NCCN Guidelines recommend surgery limited to a unilateralsalpingooophorectomy (USO; preserving the uterus and contralateral ovary) for women who wish to maintain their fertility, and standard ovarian cancer debulking surgery is recommended for those not concerned about fertility preservation.

On the contrary, in women diagnosed with stage II, III, or IV epithelial ovarian cancer, the NCCN Guidelines recommend intraperitoneal chemotherapy for first-line therapy and have been updated to include dose-dense paclitaxel (Taxol, Bristol-Myers Squibb) as a possible treatment option.

Dr. Morgan noted that in a recent clinical trial, dose-dense weekly paclitaxel with carboplatin (Paraplatin, Bristol-Myers Squibb) showed an increase in both progression-free and overall survivals when compared with conventional intraperitoneal chemotherapy of weekly carboplatin/paclitaxel.

“However, the dose-dense regimen is more toxic, and patients discontinued dose-dense paclitaxel therapy more often than those receiving standard therapy,” stated Dr. Morgan. “As with all treatment decisions, the patient needs to weigh the potential benefits and risks and discuss them thoroughly with their physician.”

Dr. Morgan discussed 2 additional phase III trials assessing bevacizumab (Avastin, Genentech/Roche) combined with carboplatin/paclitaxel in the upfront setting compared with carboplatin/paclitaxel alone. Although data regarding overall survival and quality of life have not been reported yet, the studies indicated that the median progression-free survival increased in patients receiving bevacizumab as a first-line and maintenance therapy.

“Only modest improvements in progression-free survival were observed in both of these trials. The NCCN Guidelines Panel prefers to await mature results of these trials prior to recommending the routine addition of bevacizumab to carboplatin/paclitaxel,” said Dr. Morgan.

As such, the updated NCCN Guidelines includes new language detailing the panel's view on bevacizumab encouraging participation in ongoing clinical trials that are further investigating the role of antiangiogenesis agents in the treatment of ovarian cancer, both in the upfront and recurrence settings.

Biomarkers continue to emerge as an area of interest in predicting future patterns of the disease. In patients with ovarian cancer, Dr. Morgan discussed the value of monitoring CA-125 levels in regards to a recent study comparing early versus delayed treatment of relapsed ovarian cancer.

“The results of the trial suggest that the utility of the routine monitoring of CA-125 levels is limited,” said Dr. Morgan. “The NCCN Guidelines Panel encourages patients and their physicians to actively discuss the pros and cons of CA-125 monitoring based upon these findings and have updated the NCCN Guidelines to include language supporting this recommendation.”

In conclusion, Dr. Morgan emphasized that although steady progress is being made in the treatment of ovarian cancer, further trials are necessary to investigate the role of targeted agents alone and in combination in newly diagnosed and recurrent ovarian cancer. In addition, enrollment of patients with ovarian cancer into clinical trials must be encouraged.

Second-Line TKIs Offer Expanded Treatment Options for Newly Diagnosed Patients with CML

Second-generation tyrosine kinase inhibitor (TKI) therapies approved for first-line therapy of chronic myelogenous leukemia (CML) offer newly diagnosed patients an expanded range of treatment options, according to Susan O'Brien, MD, of The University of Texas MD Anderson Cancer Center and chair of the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) Panel for CML. Dr. O'Brien emphasized the considerable advances made in the treatment of CML during her presentation of the updated NCCN Guidelines for CML at the NCCN 16th Annual Conference.

The addition of nilotinib (Tasigna, Novartis Oncology) and dasatinib (SPRYCEL, Bristol-Myers Squibb) as primary treatment options for patients with CML are the most significant updates to the NCCN Guidelines for CML, noted Dr. O'Brien. The newly approved therapies join the current standard of care, imatinib (Gleevec, Novartis Oncology), as first-line options for newly diagnosed patients.

“The development of imatinib revolutionized the treatment of CML, providing patients with a safe and effective treatment option associated with an excellent survival benefit,” said Dr. O'Brien.

However, in recent studies, dasatinib and nilotinib were associated with significantly higher response rates and reduction in the 12-month incidence of accelerated or blast phase in patients with CML. Subsequently, the FDA granted approval of dasatinib and nilotinib as a first-line therapy for newly diagnosed patients with CML. Both drugs were previously reserved for use in patients with resistance or intolerance to prior therapy, including imatinib.

In terms of monitoring response to therapy, Dr. O'Brien noted that complete cytogenetic response remains the gold standard, although patients who rapidly achieve a major molecular response also have a low rate of relapse.

“Research has shown that patients who achieve a complete cytogenetic response live longer, whereas a molecular response has not been shown to improve survival. Patients who do not achieve a complete molecular response should not be considered to have failed treatment,” clarified Dr. O'Brien.

There are clinical trials currently underway to determine if complete molecular response offers hope for treatment discontinuation or may be helpful in predicting future risk of progression or relapse.

In addition to the newly approved therapies, several agents in clinical trials show promising activity.

“Availability of more potent TKIs has widened the treatment options and, given the new agents in the pipeline, the outlook for patients with CML continues to look promising,” said Dr. O'Brien.

Jai Pausch Addresses the Fear and Anxiety Caregivers Experience in the Aftermath of Cancer Treatment for Their Loved Ones With Cancer

Caregivers and patients with cancer are not alone in grappling with feelings of fear and anxiety in the aftermath of cancer treatment, assures Jai Pausch in her new “Ask Jai” column on NCCN.com. Ms. Pausch, caregiver and widow of the late Randy Pausch, acclaimed Carnegie Mellon University professor and author of the internationally best-selling book The Last Lecture, responds to a reader's question about how caregivers can help themselves and their loved ones with cancer deal with the anxiety, depression, and sleeplessness that often accompany a loved one's diagnosis and treatment of cancer.

Because living with cancer may also mean living with a high degree of uncertainty, Ms. Pausch encourages caregivers to become aware of their anxiety levels and to have strategies for regaining control when fear seems to have taken over, something she dealt with personally as the primary caregiver for her husband. She also recommends seeking a counselor or the advice of a general practitioner who may recommend medications when appropriate to help cope with depression and sleeplessness. According to Ms. Pausch, caregivers and their loved ones can “enjoy life beyond cancer” by accepting help, raising self-awareness, and developing good coping skills. Patients and caregivers can visit NCCN.com to read the column in its entirety, as well as additional columns in the series.

In addition to the “Ask Jai” column, NCCN.com features the NCCN Guidelines for Patients as well as enhanced content for patients and caregivers. To submit a question, e-mail askjai@nccn.org.

NCCN Foundation Announces Young Investigator Awards

The NCCN Foundation, which, through private philanthropy and grants, advances NCCN's mission to improve the quality and effectiveness of care for patients with cancer, has awarded grants to 5 young investigators dedicated to advancing and discovering new treatments for cancer. The awards are the first ever made by the NCCN Foundation through its newly formed Young Investigator Awards Program. Each of the funded research initiatives will focus on assessing or improving outcomes of cancer care and carry grants of $150,000 over a 2-year period. Funding will begin August 1, 2011.

“Throughout its history, NCCN has taken a leadership role in developing standards of care for delivering state-of-the-art cancer treatment and measuring outcomes. These grants not only strengthen our overall program in this critical area, but they also contribute to nurturing the next generation of cancer researchers in this country. We are very proud that we are able to make these awards at a time when both of these issues—defining quality in cancer care and supporting science—are so important,” said William McGivney, PhD, Chief Executive Officer of NCCN.

The 2011 NCCN Foundation Young Investigator Awardees are:

• Kenneth Carson, MD, Assistant Professor of Medicine, Section of Medical Oncology, Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine for the research initiative, “NCCN Guideline adherence in veterans with diffuse large B-Cell lymphoma: predicting adherence and influence of adherence on survival.”

• Nadine Jackson McCleary, MD, PhD, Medical Oncologist, Dana-Farber Cancer Institute, Instructor of Medicine, Harvard Medical School for the research initiative, “Improving treatment outcomes of older individuals with colorectal cancer: impact of duration and onset of adjuvant chemotherapy treatment on survival and predictive utility of geriatric assessment in advanced colorectal cancer.”

• Reshma Jagsi, MD, DPhil, Assistant Professor, Department of Radiation Oncology, University of Michigan Health System for the research initiative, “A nationwide physician survey to evaluate the role of the NCCN Guidelines in cancer management recommendations.”

• Joanne Lester, PhD, CRNP, ANP-BC, AOCN, Research Scientist and Oncology Nurse Practitioner, The Ohio State University Comprehensive Cancer Center – James Cancer Hospital and Solove Research Institute; Clinical Assistant Professor, College of Nursing, Ohio State University for the research initiative, “Effect of survivorship care planning on distress: a randomized control trial with leukemia and breast cancer survivors.”

• William P. Tew, MD, Assistant Attending Physician, Gynecologic Medical Oncology Service, Memorial Sloan-Kettering Cancer Center for the research initiative, “Geriatric assessment and intervention in elderly women with ovarian cancer.”

The awardees responded to a Request for Proposal (RFP) issued by the NCCN Foundation to the 21 NCCN Member Institutions. All submissions were reviewed by a multidisciplinary panel of oncology experts, and the awardees were selected based on several key components, including scientific merit and study design.

“This is an important and exciting initiative for NCCN and its Foundation. We are very pleased to have received such a large number of excellent proposals. This allowed us to make these awards to a diverse group of top young researchers, addressing different cancer types and issues, all very much in the scope of the NCCN mission,” said Paul F. Engstrom, MD, Senior Vice President for Extramural Research Programs, Fox Chase Cancer Center, and a member of the review committee.

These awards were made possible via contributions from Amgen Inc., Genentech, Inc., Millennium Pharmaceuticals, and Pfizer Oncology.

NCCN Hematologic Malignancies Congress Aims to Further Treatment in China

As part of the 4th Annual Asia Scientific Congress held in Shanghai, China, NCCN convened the NCCN Hematologic Malignancies Congress on April 10, 2011. The collaborative Congress presented to more than 75 Chinese hematologists and aimed to further the treatment of hematologic malignancies in China.

Sessions from the Congress included opening remarks from Professor Zhixiang Shen and presentations on chronic myelogenous leukemia, multiple myeloma, and myelodysplastic syndromes. Presenting NCCN Guidelines Panel Members included Dr. Jerald P. Radich, of Fred Hutchinson Cancer Research Center/Seattle Cancer Care Alliance, and Dr. Seema Singhal, of Robert H. Lurie Comprehensive Cancer Center of Northwestern University. During these presentations, a consensus discussion resulted in minor adjustments to be made to the NCCN Guidelines, China Edition for Multiple Myeloma.

As China does not have access to the same drugs listed in the NCCN Guidelines, an ongoing focus of the Congress involves adapting the information in the NCCN Guidelines to the Chinese demographic. Consequently, NCCN and Chinese hematologists will continue working together to reduce the gaps in treatment of hematologic malignancies that exist in China.