The SWOG S1400 Lung-MAP trial uses a multi-drug, targeted screening approach to match patients with promising new cancer treatments based on their unique tumor profiles.
The Lung Master Protocol trial -- Lung-MAP, or SWOG S1400 -- is activated today, allowing sites across the country to begin enrolling patients.
Lung-MAP is a multi-drug, multi-arm, biomarker-driven clinical trial for patients with advanced squamous cell lung cancer. Squamous cell carcinoma represents about a quarter of all lung cancer diagnoses, but there are currently few treatment options beyond surgery for the disease. The trial will use genomic profiling to match patients to one of several different investigational treatments that are designed to target the genomic alterations found to be driving the growth of their cancer. This innovative approach to clinical testing should both improve access to promising drugs for patients and ease the significant recruitment and infrastructure burdens on researchers involved in traditional clinical trials.
Lead Study Chairs for the trial are Vassiliki A. Papadimitrakopoulou, M.D., Professor in the Department of Thoracic/Head and Neck Medical Oncology at MD Anderson; David R. Gandara, M.D., Director of the Thoracic Oncology Program at UC Davis and Chair of the SWOG Lung Committee; and Roy S. Herbst, M.D., Ph.D., who is Chief of Medical Oncology at Yale.
Mary Redman, Ph.D., of the SWOG Statistical Center in Seattle, directs the biostatistical work on the study.
Fred R. Hirsch, M.D., Ph.D., of the University of Colorado and Philip C. Mack, Ph.D., of UC Davis, are study co-chairs for translational medicine, and Lawrence Schwartz, M.D., of Columbia University and Chair of the SWOG Imaging Committee, is study chair for imaging.
Lung-MAP is opening NCTN-wide with all four of the adult NCTN network groups participating. Alliance Study Chair is Everett Vokes, M.D., of University of Chicago; ECOG-ACRIN Study Chair is Suresh Ramalingam, M.D., of Emory University; and NRG Study Chair is Jeff Bradley, M.D., of Washington University.
The study is the product of a unique public-private collaboration among SWOG, the National Cancer Institute (NCI), Friends of Cancer Research (Friends), the Foundation for the National Institutes of Health (FNIH), five pharmaceutical companies (Amgen, Genentech, Pfizer, AstraZeneca, and AstraZeneca’s global biologics R&D arm, MedImmune), and Foundation Medicine.
The trial will initially test five experimental drugs -- four targeted therapies and an anti-PD-L1 immunotherapy. It is anticipated that between 600 and 1200 patients will be screened per year for over 200 cancer-related genes for genomic alterations. The results of this test will be used to assign each patient to the trial arm that is best matched to their tumor’s genomic profile.
“Lung-MAP represents the first of several planned large, genomically-driven treatment trials that will be conducted by NCI’s newly formed National Clinical Trials Network (NCTN),” said Jeff Abrams, M.D., Associate Director of NCI’s Cancer Therapy Evaluation Program. “The restructuring and consolidation of NCI’s large trial treatment program, resulting in the formation of the NCTN, is quite timely, as it now can offer an ideal platform for bringing the benefits of more precise molecular diagnostics to cancer patients in communities large and small.”
Lung-MAP aims to establish a model of clinical testing that more efficiently meets the needs of both patients and drug developers. Whereas a typical clinical trial for a targeted therapy tests each potential patient for a single biomarker and enrolls only a portion—sometimes a very small portion—of patients tested, Lung-MAP will simultaneously test patients for many biomarkers in order to assess compatibility with several different experimental treatments. Patients tested will then be enrolled into one of Lung-MAP’s five trial arms.
Lung-MAP should make it easier for patients and researchers to find one another. It will also be more flexible than traditional clinical trial models. Where typical clinical trials require the development of new protocols for each new drug tested, Lung-MAP uses a single “master protocol,” which can be amended as needed as drugs enter and exit the trial, preserving infrastructure and patient outreach efforts.
The trial will be conducted at medical centers across the United States by NCI’s NCTN, led by SWOG, and partly funded by NCI through its Cancer Therapy Evaluation Program. Significant additional funding will be provided by the participating companies as part of a partnership managed by FNIH that also involves the Food and Drug Administration (FDA), Friends, and other patient advocacy organizations. The trial infrastructure is capable of testing as many as 5-7 additional drugs over the next 5 years, and will cost up to $160 million.
A phase III clinical trial finds that the drugs bevacizumab and cetuximab are equally effective when either is combined with standard chemotherapy for treating patients with metastatic colorectal cancer who have not previously been treated. When combined with chemotherapy, both drugs delayed worsening of cancer and extended patients lives by similar lengths of time. Results are reported today at the plenary session of the annual meeting of the American Society of Clinical Oncology (ASCO) in Chicago (Abstract LBA3).
Treatment helps young women preserve their fertility during breast cancer chemotherapy
[May. 30, 2014]
Researchers have found that young women with breast cancer were able to better preserve their fertility during cancer treatments by using hormone-blocking drug injections that put them into temporary menopause. The results announced today at the annual meeting of the American Society of Clinical Oncology (ASCO) in Chicago are from the Prevention of Early Menopause Study (POEMS), a clinical trial sponsored by the National Cancer Institute (NCI), part of the National Institutes of Health (ASCO late breaking abstract #505). Women receiving the injections were only about one-third as likely to experience ovarian failure, a common long-term toxicity of chemotherapy treatments, and were more than twice as likely to have a normal pregnancy after their cancer treatment compared to women in the trial who did not receive the injections.
In POEMS, premenopausal women with hormone-receptor negative breast cancer ages 18 to 49 were randomly assigned to receive standard chemotherapy with or without goserelin every four weeks. Goserelin is a drug that disrupts the body’s hormonal feedback systems, resulting in reduced estrogen production, which puts the women into a chemical menopause. Under usual use, that chemical menopause is reversible; POEMS was carried out to see if the treatment allowed the women to recover fertility after cancer treatment while not interfering with the cancer treatment itself.
The researchers compared the ovarian failure rate of the women two years after entering the study and found that 22 percent of patients on the standard therapy had ovarian failure (15 of 69 patients) compared to 8 percent of those who also had goserelin treatment (5 of 66 patients). Of the 218 patients enrolled in the trial, 12 patients on the standard arm (11 percent) became pregnant vs 22 patients on the goserelin treatment arm (21 percent).
"This trial was the first demonstration of improved fertility prospects and more successful pregnancies when goserelin was used,” said Halle Moore, M.D., Cleveland Clinical Foundation and the lead investigator for POEMS. “Premenopausal women beginning chemotherapy for early breast cancer should consider this new option to prevent premature ovarian failure.”
The trial was conducted by SWOG, one of NCI’s five National Clinical Trial Network groups, with the collaboration of the ECOG-ACRIN Cancer Research Group and the Alliance for Clinical Trials in Oncology, and international access provided through the International Breast Cancer Study Group which includes the Australia New Zealand Breast Cancer Group.
The standard approach to preserving fertility in young female cancer patients is to harvest and store ovarian tissue, ovarian follicles, or embryos prior to cancer treatment. “Finding a simple and accessible way to protect fertility in young breast cancer patients while not harming cancer outcomes is an important issue,” said Lori Minasian, M.D., deputy director of the NCI Division of Cancer Prevention and one of the researchers on POEMS.
Fertility-preserving treatment was not expected to have an effect on cancer outcomes and this data was analyzed only to ensure there were no detrimental effects from that treatment. “We found that, in addition to reducing the risk of early menopause, and all of the symptoms that go along with menopause, goserelin was very safe,” said Kathy Albain, M.D., of Loyola University Medical Center and senior author of the ASCO abstract. “I think these findings are going to change our clinical practice.”
In the United States alone almost 49,000 women under age 50 are diagnosed with invasive breast cancer each year; nearly 11,000 of those are under age 40. Of this population, about 15 percent have breast cancer that is hormone-receptor negative, meaning the disease does not feed on hormones or respond to therapy against hormones.
Reference: Moore HCF, et al. Prevention of Early Menopause Study (POEMS)/S0230, a Phase III Trial of LHRH Agonist Administration During Chemotherapy to Reduce Ovarian Failure in Early Stage, Hormone Receptor-Negative Breast Cancer: An International Intergroup Trial of SWOG, IBCSG, ECOG, and CALGB (Alliance). ASCO abstract LBA505.
POEMS was coordinated by SWOG, an NCI-supported cancer research cooperative group that designs and conducts multidisciplinary clinical trials to improve the practice of medicine in preventing, detecting, and treating cancer, and to enhance the quality of life for cancer survivors. An international study, POEMS was available worldwide through the International Breast Cancer Study Group, and supported by grants from the U.S. National Cancer Institute and in part by the Australia and New Zealand Breast Cancer Trials Group, the Breast Cancer Institute of Australia, and AstraZeneca Pharmaceuticals.
Here are details on, and links to, the ASCO 2014 abstracts SWOG investigators will be presenting or have contributed to.
Lisa A. Kachnic, M.D., president-elect of American Board of Radiology
[Mar. 14, 2014]
The American Board of Radiology (ABR) has elected SWOG Executive Officer Lisa A. Kachnic, MD, as president-elect. She will succeed current ABR President-Elect Milton J. Guiberteau, MD, who will become ABR president on July 1, 2014. Dr. Kachnic has served as an ABR trustee since 2010.
Dr. Kachnic is chair of the Department of Radiation Oncology at Boston Medical Center and professor of radiation oncology at Boston University School of Medicine. She also serves on the radiation oncology faculty at Massachusetts General Hospital. She earned her undergraduate degree from Boston College and her medical degree from Tufts University. Dr. Kachnic completed her residency in radiation oncology at Massachusetts General Hospital, serving in her last year as chief resident.
Dr. Kachnic’s areas of interest include gastrointestinal (GI) malignancies, image-guided radiation delivery, and outcomes/symptoms management research. She is actively involved in the Radiation Therapy Oncology Group’s (RTOG’s) GI and Outcome strategic committees and has been the RTOG chairperson of symptom management since 2003. At SWOG, in addition to her role as executive officer, she also directs GI radiation oncology and is discipline vice-chair of the Radiation Therapy Committee. As such, she has been given the opportunity to serve as principal or co-principal investigator on several national trials. Dr. Kachnic has been awarded funding as an NCI principal investigator and is the 2008 recipient of the first RTOG “Next Generation Investigator” Award.
SELECT sub-study: Selenium supplements can increase prostate cancer risk
[Feb. 21, 2014]
A sub-study of a selected cohort of men in the SWOG-led SELECT prevention study finds that while selenium supplements did not change prostate cancer risk across the full group of participants, men who started the study with high selenium levels increased their prostate cancer risk by taking selenium supplements.
The new work, published in the February 21st issue of the Journal of the National Cancer Institute, also offers insight into SELECT results that found vitamin E supplements alone increased prostate cancer risk, but the combination of vitamin E and selenium did not.
The case-cohort study was led by Alan Kristal, Dr.P.H., of the Fred Hutchinson Cancer Research Center in Seattle. A press release from that institution quotes Kristal as saying "Men using these supplements should stop, period. Neither selenium nor vitamin E supplementation confers any known benefits – only risks."
The Selenium and Vitamin E Cancer Prevention Trial, or SELECT, enrolled more than 35,000 healthy men from 2001 through 2003 to test whether vitamin E and selenium supplementation, either alone or in combination, could lower prostate cancer risk. The study was closed early because it became clear the supplements provided no benefit. Long-term follow-up on the study found that vitamin E supplements increased men's prostate cancer risk by 17%.
The National Cancer Institute, which funded the SELECT study, has updated it's authoritative SELECT Questions & Answer page to incorporate these latest findings.
Changes in NCI programs, under both CTEP and DCP, mean site membership categories within SWOG will be changing somewhat for some of our sites. The latest information we have is presented in these three tables, which detail the relationships among the proposed SWOG membership categories. Although these categories are not yet set in stone, for most of our core members and affiliates, little will change.
There is mounting evidence that elevated levels of circulating tumor cells (CTCs) in the bloodstream of women being treated for metastatic breast cancer are associated with a poor prognosis.
Researchers on the SWOG S0500 clinical trial sought to learn whether elevated CTC levels soon after starting chemotherapy could be used as an early indicator -- earlier than other indicators such as clinical evidence of progression -- that the given therapy was not working and that it was time to switch to an alternate treatment. They found that though an elevated CTC level (>= 5 cells per 7.5 mL of blood) at a first follow up visit after starting chemotherapy was associated with a poorer prognosis for the patient, switching at that early point to an alternate chemotherapy regimen did not generally prove beneficial to these patients.
Performing early stem cell transplants in patients with aggressive non-Hodgkin’s lymphoma does not improve overall survival in high-risk patients, SWOG-9704 has found. But early transplantation does appear to be beneficial among a small group of patients who are at the very highest risk. Results are published in the New England Journal of Medicine.
Patrick Stiff, MD, director of Loyola University Medical Center’s Cardinal Bernardin Cancer Center and lead author on the NEJM paper, said this finding "hopefully will trigger discussions between such patients and their physicians as to the feasibility of doing early transplants."
The study was developed by the SWOG cancer research cooperative group and funded by the National Cancer Institute. Stiff is chair of the SWOG Bone Marrow and Stem Cell Transplantation Committee.
Data from up to 18 years of follow-up of men on the Prostate Cancer Prevention Trial show finasteride reduced the overall risk of a prostate cancer diagnosis by about one-third, raised the risk of a high-grade diagnosis slightly, and had no effect on overall survival times.