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Sinicrope F.A.,North Central Cancer Treatment Group | Foster N.R.,North Central Cancer Treatment Group | Yothers G.,National Surgery Adjuvant Breast and Bowel Project | Benson A.,Eastern Cooperative Oncology Group | And 6 more authors.
Cancer | Year: 2013

BACKGROUND: Although obesity is an established risk factor for developing colon cancer, its prognostic impact and relation to patient sex in colon cancer survivors remains unclear. METHODS: The authors examined the prognostic and predictive impact of the body mass index (BMI) in patients with stage II and III colon carcinoma (N = 25,291) within the Adjuvant Colon Cancer Endpoints (ACCENT) database. BMI was measured at enrollment in randomized trials of 5-fluorouracil-based adjuvant chemotherapy. Association of BMI with the time to recurrence (TTR), disease-free survival (DFS), and overall survival (OS) were determined using Cox regression models. Statistical tests were 2-sided. RESULTS: During a median follow-up of 7.8 years, obese and underweight patients had significantly poorer survival compared with overweight and normal-weight patients. In a multivariable analysis, the adverse prognostic impact of BMI was observed among men but not among women (Pinteraction =.0129). Men with class 2 and 3 obesity (BMI ≥35.0 kg/m2) had a statistically significant reduction in DFS (hazard ratio [HR], 1.16; 95% confidence interval [CI], 1.01-1.33; P =.0297) compared with normal-weight patients. Underweight patients had a significantly shorter TTR and reduced DFS (HR, 1.18; 95% CI, 1.09-1.28; P <.0001) that was more significant among men (HR, 1.31; 95% CI, 1.15-1.50; P <.0001) than among women (HR, 1.11; 95% CI, 1.01-1.23; P =.0362; Pinteraction =.0340). BMI was not predictive of a benefit from adjuvant treatment. CONCLUSIONS: Obesity and underweight status were associated independently with inferior outcomes in patients with colon cancer who received treatment in adjuvant chemotherapy trials. © 2013 American Cancer Society.


News Article | December 16, 2016
Site: www.eurekalert.org

LUGANO-SINGAPORE, 17 December, 2016 - The first data on rare sarcomas in Asian patients is presented in three studies today at the ESMO Asia 2016 Congress in Singapore. Just half of patients with advanced angiosarcoma received chemotherapy even though it improved overall survival. CIC-rearranged sarcomas are shown to have a much worse prognosis than BCOR-rearranged sarcomas and clinical features are identified to aid accurate diagnoses. Angiosarcoma is the focus of two studies conducted by the newly formed Asian Sarcoma Consortium (ASC).1,2 This heterogeneous cancer has two distinct subtypes: elderly patients with scalp/cutaneous disease and a younger cohort with visceral disease typically in the liver, vascular systems, and breast. Treatment is challenging since the disease tends to be infiltrative, making surgery with clear margins difficult, while radiation is a poor option for tumours on the scalp and face. Chemotherapy has demonstrated activity in angiosarcoma but long term remission is rare. Both studies retrospectively included patients attending eight sites in six countries during 1990 to 2016. The first study outlines the epidemiology, real world treatment and clinical outcomes of angiosarcoma in Asia. The median age of the 423 patients was 67 years, about 60% had cutaneous angiosarcoma (they were more likely to be older, male, and have localised disease), while 40% had visceral angiosarcoma. In the localised setting, only about 60% of patients underwent surgery, but this was significantly lower in the cutaneous (55%) than visceral (75%) cohort. In those who underwent surgery, negative margins were only achieved in approximately 70% of cases. Close to half of patients who underwent surgery relapsed. Median relapse free survival was just 12.3 months with no statistical difference between the cutaneous (12.9 months) versus visceral (9.5 months) groups. Patients were more likely to relapse if they were more than 65 years old or had positive surgical margins. In the advanced setting, only about half of patients received chemotherapy. Median overall survival was 9.5 months with no significant difference between cutaneous (11.5 months) and visceral (8.3 months) groups. ECOG (Eastern Cooperative Oncology Group) performance status was an independent predictor of survival. However, after adjusting for ECOG performance status, overall survival was significantly better in patients who received chemotherapy than those who did not. "This is one of the largest studies in angiosarcoma and we found that overall prognosis was poor," said lead author Professor Richard Quek, deputy head and senior consultant, National Cancer Centre Singapore. "In patients with localised disease, negative surgical margin was prognostic for relapse free survival yet it was only achieved in 70% of patients. Neoadjuvant (pre-operative) treatment, be it chemotherapy or radiation, might enhance resectability of these tumours and thereby improve survival outcomes." Quek continued: "In patients with advanced disease we demonstrated that after adjusting for ECOG performance status, chemotherapy was associated with improved overall survival. But only half of our patients actually received chemotherapy, hence it would be important to understand the reasons behind this low treatment rate. Could these be physician-related factors? And if so, is more sarcoma-related continuing medical education needed to enhance care for our patients?" The second angiosarcoma study outlined the clinical characteristics and treatment of 277 patients with advanced metastatic or unresectable disease. The median age was 64 years. The predictors of better prognosis were younger age, female sex, and cutaneous (rather than visceral) disease. Use of chemotherapy gradually increased over the 20-year period, with a preference for paclitaxel and liposomal doxorubicin over other treatments. Progression-free survival in patients receiving at least one line of chemotherapy was 3.8 months. Overall survival was 8.3 months but was significantly higher in patients who received at least one line of palliative chemotherapy (11.5 months) than those who did not (4.4 months). "It's the first time we have data on expected survival for Asian patients with advanced metastatic or unresectable angiosarcoma," said lead author Dr Tom Chen, attending physician, National Taiwan University Hospital, Taipei, Taiwan. "This data will help us to develop clinical trials and new treatments for Asian angiosarcoma patients." The third study focused on Ewing sarcoma-like small round cell sarcomas.3 Ewing sarcoma is molecularly characterised by a EWSR1 gene alteration or FUS rearrangement. Small round cell sarcomas without these molecular characteristics are designated "Ewing sarcoma-like" disease. Recent molecular genetic studies have identified CIC-rearranged sarcoma (CIC-DUX4, CIC-DUX4L, CIC-FOXO4) and BCOR-rearranged sarcoma (BCOR-CCNB3, BCOR-MAML3, ZC3H7B-BCOR) among these Ewing sarcoma-like small round cell sarcomas. The study presented today describes the clinical characteristics and treatment outcomes of these two sarcomas. The study included 17 patients with CIC sarcoma, of whom 12 were male. Median age was 22 years, all cases were soft tissue tumours, and 59% of patients had local pain. The seven BCOR sarcoma patients were all male. Median age was 14 years and cases included bone and soft tissue tumours. The five-year overall survival rate was 28.2% for CIC sarcoma and 100% for BCOR sarcoma. Metastases were present in 71% of CIC patients at the initial visit and none of the BCOR patients. Only 29% of CIC patients responded to chemotherapy compared to 75% of BCOR patients. "CIC-rearranged sarcomas have a much worse prognosis than BCOR-rearranged sarcomas," said lead author Dr Makoto Endo, attending physician, National Cancer Centre, Tokyo, Japan. "CIC and BCOR sarcomas were previously classified as the same tumour. Our research will help us to make a precise diagnosis and should improve the management of these patients." Commenting on the studies, Professor Thomas Brodowicz, programme director, Bone and Soft Tissue-Sarcoma Unit, Medical University Vienna, Austria, said: "The two studies on angiosarcoma show that immediate progression-free survival and overall survival are low, which reflects the aggressiveness of this disease. It would be useful to have a more detailed breakdown of the patients - for example, the treatment and outcomes of primary angiosarcoma versus secondary, which forms at the site of radiation treatment for a previous cancer. It would also be helpful to know whether paclitaxel is more effective when taken every three weeks or weekly, which has an antiangiogenic effect that could be beneficial in angiosarcoma." He continued: "The study by Dr Endo provides practice-changing information. It shows that Ewing sarcoma-like small round cell sarcomas can be further categorised by their specific mutations, which have a strong prognostic impact. This should help us to tailor treatment."


BEERSE, Belgien--(BUSINESS WIRE)--Janssen-Cilag International NV meldete heute die Veröffentlichung von Daten, die ein radiologisch nachgewiesenes progressionsfreies Überleben (rPFS) von 16,5 Monaten (95% CI, 13,5–20,0) und eine Behandlungsdauer von 11,6 Monaten (95% CI, 10,2–12,8) bei mit ZYTIGA® (Abirateronacetat) plus Prednison (AAP) behandelten Männern unter Alltagsbedingungen, außerhalb von klinischen Studien, zeigen. In der Studie wurden Männer beurteilt, die wegen metastasiertem, kastrationsresistentem Prostatakrebs (mCRPC) mit keinen oder nur leichten Symptomen im Anschluss an eine Androgendeprivationstherapie (ADT) behandelt wurden.1 Diese wertvollen Erkenntnisse zeigten sich trotz der Alltagsbedingungen der Studienpopulation, darunter Patienten mit schlechter Prognose oder schwer zu behandelnde Patienten, die in der Regel von klinischen Studien ausgeschlossen sind. Diese Daten sind Teil eines umfassenden Portfolios im Bereich Real-World Evidence (RWE), das Janssen auf dem diesjährigen American Society of Clinical Oncology Genitourinary Cancers Symposium (ASCO GU) in Orlando, Florida, vorgestellt hatte. „Die Evidenzforschung unter Alltagsbedingungen ist in der patientenbezogenen klinischen Praxis zentral, da sie den Ärzten hilft, besser auf die Bedürfnisse der Patienten einzugehen. Sie ergänzt Daten, die aus klinischen Studien gewonnen wurden, um zu einem besseren Verständnis der Behandlungsergebnisse, des Krankheitsmanagements und des Einflusses auf die Lebensqualität bei breiten Patientenpopulationen, darunter solche mit Komorbiditäten, beizutragen“, sagte Dr. Martin Bögemann, Urologie, Universitätsklinikum Münster, Münster, Deutschland. „Es ist hilfreich festzustellen, dass neue Daten zu Behandlungsergebnissen bei Patienten unter Alltagsbedingungen diejenigen bestätigen, die im Umfeld klinischer Studien gewonnen wurden. Diese neuen Erkenntnisse ergänzen den wachsenden Bestand an Nachweisen unter Alltagsbedingungen, der in Europa zur Verfügung steht und der uns mehr und mehr hilft, die besten Therapien zu wählen, um die Behandlungsergebnisse für die Patienten zu transformieren.“ Patienten der Zulassungsstudie COU–AA–302 erzielten eine mediane Behandlungsdauer von 13,8 Monaten (IQR, 8,3–27,4) und ein medianes rPFS von 16,5 Monaten (95% CI, 13,8–16,8).1,2,3,4 Die Ergebnisse waren in beiden Settings ähnlich, obwohl fast 10 % der Patienten in der RWE-Studie viszerale Metastasen (Metastasen an inneren Organen, das heißt der Leber und/oder Lungen) und/oder einen Performance-Status der Eastern Cooperative Oncology Group (ECOG) von 2 bis 3 (nicht arbeitsfähig, Selbstversorgung jedoch ganz oder teilweise möglich) hatten.1 Diese Patienten wurden nicht in die COU-AA-302-Studie einbezogen.4 Dr. Ivo Winiger-Candolfi, Oncology Therapeutic Area Lead, Janssen Europe, Middle East and Africa (EMEA), sagte: „Evidenz unter Alltagsbedingungen ist äußerst wertvoll, da sie Erkenntnisse bietet, die klinische Studien ergänzen und bedeutende Einblicke in die Leistung und den Einsatz eines Arzneimittels in realen medizinischen Settings gibt, was schließlich in die bestmögliche Behandlung der Patienten umgesetzt wird. Dies wird insbesondere bei Prostatakrebs deutlich, da dies die häufigste Krebserkrankung bei Männern ist, die zudem eine vielfältige Patientenpopulation mit unterschiedlichem Behandlungsbedarf aufweist. Janssen unterstützt weiterhin die Evidenzforschung unter Alltagsbedingungen, um dabei zu helfen, die Behandlungsergebnisse der Patienten zu transformieren, damit Krebs in der Zukunft besser beherrschbar sein wird.” Prostatakrebs ist die am häufigsten diagnostizierte Krebsart bei Männern, mit über 400.000 neu diagnostizierten Fällen jährlich in Europa.6 Die neuesten Prostatakrebs-Zahlen belegen, dass gegenwärtig drei Millionen Männer in Europa von dieser Erkrankung betroffen sind.7 Die Boegemann-et-al.-Studie ist eine retrospektive Untersuchung der Akten (Chart Review) von 224 Patienten mit mCRPC mit keinen oder nur leichten Symptomen nach einer Androgendeprivationstherapie, die mit ZYTIGA (Abirateronacetat) plus Prednison (AAP) in 18 Zentren in Belgien, Deutschland und Großbritannien behandelt wurden.1 Das Prostatakrebsregister wurde 2013 als langfristige Initiative von Janssen ins Leben gerufen, um die optimale Behandlung von mCRPC in der Routinepraxis zu ermitteln. Das Register wurde in Zusammenarbeit mit Fachärzten auf dem Gebiet des mCRPC konzipiert. Die beobachteten Patienten werden in diversen Umgebungen in der Onkologie und Urologie behandelt, woraus sich ein Bild der routinemäßigen klinischen Praxis ergeben soll. 8 1 Boegemann et al. Real-World Treatment with Abiraterone Acetate in Chemotherapy-Naïve Metastatic Castration-Resistant Prostate Cancer Patients. Poster präsentiert auf dem American Society of Clinical Oncology Genitourinary Symposium 2017, 16. bis 18. Februar, Orlando, Florida, USA. Posterpräsentation. ASCO GU Abstract #239. Zuletzt abgerufen im Februar 2017. 2 Rathkopf et al. Updated Interim Efficacy Analysis and Long-term Safety of Abiraterone Acetate in Metastatic Castration-resistant Prostate Cancer Patients Without Prior Chemotherapy (COU-AA-302). EUROPEAN UROLOGY 2014; 66: 815-825. Zuletzt abgerufen im Februar 2017. 3 Ryan CJ, Smith MR, de Bono JS, et al. Abiraterone in Metastatic Prostate Cancer without Previous Chemotherapy. N Engl J Med. 2013 Jan; 368(2): 138 - 48. 4 Ryan C.J et al. Abiraterone acetate plus prednisone versus placebo plus prednisone in chemotherapy-naive men with metastatic castration-resistant prostate cancer (COU-AA-302): final overall survival analysis of a randomised, double-blind, placebo-controlled phase 3 study. The Lancet Oncology. 2015; 16, 2: p152-160. Verfügbar unter: http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(14)71205-7/abstract. Zuletzt abgerufen im Februar 2017. 5 Chowdhury S et al. The Prostate Cancer Registry: Real-World outcomes in first-line treatment of metastatic castration-resistant prostate cancer (mCRPC). Poster präsentiert auf dem American Society of Clinical Oncology Genitourinary Symposium 2017, 16. bis 18. Februar, Orlando, Florida. Posterpräsentation. ASCO GU abstract #212. Zuletzt abgerufen im Februar 2017. 6 Ferlay J et al. Cancer incidence and mortality patterns in Europe: Estimates for 40 countries in 2012. European Journal of Cancer. 2013; 49: p1374–1403. Zuletzt abgerufen im Februar 2017. 8 Chowdhury S et al. The Prostate Cancer Registry: First Results from an International, Prospective, Observational Study of Men with Metastatic Castration- Resistant Prostate Cancer (mCRPC). Poster präsentiert auf dem Europäischen Krebskongress 2015, 25. bis 29. September, Wien, Österreich. Posterpräsentation. ECC abstract #2548. Verfügbar unter: https://www.europeancancercongress.org/Scientific-Programme/Abstract-search?abstractid=21001. Zuletzt abgerufen im Februar 2017. 10 Hoy, SM. et al. Abiraterone Acetate: A review of its use in patients with metastatic castration-resistant prostate cancer drugs. Drugs 2013; 73:2077-2091. Zuletzt abgerufen im Februar 2017. 11 Ritch, CR. Cookson, MS. Advances in the management of castration resistant prostate cancer. BMJ. 2016 Oct 17;355:i4405. Doi: 10.1136/bmj.i4405. Zuletzt abgerufen im Februar 2017. 12 Ye,D. A phase 3, double-blind, randomized placebo-controlled efficacy and safety study of abiraterone acetate in chemotherapy-naïve patients with mCRPC in China, Malaysia, Thailand and Russia. Asian Journal of Urology. 2017.Doi.org/10.1016/j.ajur.2017.01.002. Zuletzt abgerufen im Februar 2017


News Article | December 19, 2016
Site: www.eurekalert.org

Bottom Line: Among women with breast cancer who received a type of chemotherapy called an anthracycline, those who had a certain genetic biomarker had a significantly increased risk for having anthracycline-induced congestive heart failure. Journal in Which the Study was Published: Clinical Cancer Research, a journal of the American Association for Cancer Research. Author: Bryan P. Schneider, MD, associate professor of medicine at the Indiana University Melvin and Bren Simon Cancer Center in Indianapolis. Background: Schneider explained that the decision to undergo chemotherapy for breast cancer is not always clear cut because each patient has a different risk of relapse and different tolerance to potential adverse effects of treatment. As a result, the more information a patient and his or her oncologist have about the potential risks and benefits of treatment the better prepared they are to make good treatment decisions, he noted. "Anthracyclines such as doxorubicin, which are widely used chemotherapeutic agents, cause congestive heart failure in about 1 to 2 percent of patients," continued Schneider. "Knowing which patients are at increased risk for this life-threatening effect of anthracycline chemotherapy is important to help oncologists counsel patients about their personal risks and benefits of such treatment." How the Study Was Conducted and Results: Schneider and colleagues analyzed genome-wide association data from 3,431 women with breast cancer who received doxorubicin as part of treatment received through enrollment in the phase III Eastern Cooperative Oncology Group (ECOG) 5103 clinical trial and for whom heart assessment data were available. Among these patients, 68 (2 percent) had cardiologist-adjudicated congestive heart failure. Because the majority of those who had cardiologist-adjudicated congestive heart failure (51) were European-American, the researchers limited the genetic association analysis to European-Americans. They identified several SNPs associated with risk of anthracycline-induced congestive heart failure. After looking at the chromosomal location of the SNPs, the researchers chose two of the top SNPs for validation in independent data sets. One of the two SNPs, rs28714259 was associated with risk of anthracycline-induced congestive heart failure among 2,415 women with breast cancer who received doxorubicin as part of treatment received through enrollment in the phase III ECOG 1199 clinical trial. It was also associated with low ventricular ejection fraction, which is a sign of heart damage, among 828 women with breast cancer who received doxorubicin as part of treatment through enrollment in the phase III BEATRICE clinical trial. Author Comment: "We found that the A allele of the single nucleotide polymorphism (SNP) rs28714259 was associated with increased risk of anthracycline-induced congestive heart failure among women with breast cancer," said Schneider. "Adding information gained from testing for this SNP to currently used clinical information could help oncologists provide a more precise prediction of the risks and benefits of anthracycline chemotherapy for patients with breast cancer. We are currently further testing this finding in patients receiving anthracyclines at the Indiana University Melvin and Bren Simon Cancer Center to better understand its contribution to heart failure risk in the face of other known risk factors and comorbidities." Limitations: According to Schneider, the study has two main limitations. First, not all of the clinical trials used the same method for assessing heart damage with corresponding long-term data. Second, the number of patients who had heart damage was relatively low because it is a rare adverse event. "As a result, additional studies in other patient groups and in the real-world setting of the clinic, as we are doing, are needed to confirm the association," Schneider said. Funding & Disclosures: The study was conducted by the ECOG-ACRIN Cancer Research Group [ACRIN (American College of Radiology Imaging Network)] and supported by funds from the Public Health Service, Susan G. Komen for the Cure, the Conquer Cancer Foundation, the Breast Cancer Research Foundation, the National Cancer Institute, the National Institutes of Health, and the Department of Health and Human Services. Schneider declares no conflicts of interest. To interview Bryan P. Schneider, contact Julia Gunther at julia.gunther@aacr.org or 215-446-6896. About the American Association for Cancer Research Founded in 1907, the American Association for Cancer Research (AACR) is the world's first and largest professional organization dedicated to advancing cancer research and its mission to prevent and cure cancer. AACR membership includes more than 37,000 laboratory, translational, and clinical researchers; population scientists; other health care professionals; and patient advocates residing in 108 countries. The AACR marshals the full spectrum of expertise of the cancer community to accelerate progress in the prevention, biology, diagnosis, and treatment of cancer by annually convening more than 30 conferences and educational workshops, the largest of which is the AACR Annual Meeting with nearly 19,500 attendees. In addition, the AACR publishes eight prestigious, peer-reviewed scientific journals and a magazine for cancer survivors, patients, and their caregivers. The AACR funds meritorious research directly as well as in cooperation with numerous cancer organizations. As the Scientific Partner of Stand Up To Cancer, the AACR provides expert peer review, grants administration, and scientific oversight of team science and individual investigator grants in cancer research that have the potential for near-term patient benefit. The AACR actively communicates with legislators and other policymakers about the value of cancer research and related biomedical science in saving lives from cancer. For more information about the AACR, visit http://www. .


Vesole D.H.,Second Street | Oken M.M.,Northwestern Hospital | Heckler C.,University of Rochester | Greipp P.R.,Mayo Medical School | And 3 more authors.
Leukemia | Year: 2012

Multiple myeloma (MM) is a malignancy of clonal plasma cells, resulting in an increased production of ineffective immunoglobulins with suppression of non-involved immunoglobulins. Patients with MM are at increased risk of infectious complications, particularly streptococcal and staphylococcal infections. This study evaluated the impact of prophylactic antibiotics on the incidence of serious bacterial infections (SBIs) during the first 2 months of treatment in patients with newly diagnosed MM. Patients with MM receiving initial chemotherapy were randomized on a 1:1:1 basis to daily ciprofloxacin (C; 500mg twice daily), trimethoprim-sulfamethoxazole (T; DS twice daily) or observation (O) and evaluated for SBI (Eastern Cooperative Oncology Group ≥grade 3) for the first 2 months of treatment. From July 1998 to January 2008, 212 MM patients were randomized to C (n=69), T (n=76) or O (n=67). The incidence of SBI was comparable among groups: C=12.5%, T=6.8% and O=15.9%; P=0.218. Further, any infection during the first 2 months was also comparable (20% vs 23% vs 22%, respectively, P=0.954). We demonstrate that prophylactic antibiotics did not decrease the incidence of SBI (≥grade 3) within the first 2 months of treatment. We conclude that routine use of prophylactic antibiotics should not be mandated for patients receiving induction chemotherapy. © 2012 Macmillan Publishers Limited. All rights reserved.


News Article | December 12, 2016
Site: globenewswire.com

SAN RAMON, Calif., Dec. 12, 2016 (GLOBE NEWSWIRE) -- Galena Biopharma, Inc. (NASDAQ:GALE), a biopharmaceutical company committed to the development and commercialization of hematology and oncology therapeutics that address unmet medical needs, today announced that two posters were presented at the San Antonio Breast Cancer Symposium (SABCS). “The poster for NeuVax in patients with DCIS presents the Phase 2 clinical trial planned to assess the NeuVax effect in the most common type of non-invasive breast cancer in the U.S.,” said Bijan Nejadnik, M.D., Executive Vice President and Chief Medical Officer.  “Despite high cure rates with the current standard of care treatments for DCIS, some patients still develop recurrences and may advance to breast cancer. The primary endpoint for the Phase 2 VADIS trial is immunologic, evaluating NeuVax-specific cytotoxic T-cells and whether long-lasting immunity is induced to suppress the growth of DCIS cells.  We are appreciative of the efforts of Dr. Beth Mittendorf and her team, and the National Cancer Institute, as we look to advance NeuVax into this new and important indication.” The poster, entitled, “VADIS trial: Phase 2 trial of the nelipepimut-S peptide vaccine in women with DCIS of the breast,” presented the trial design for the planned, Phase 2 investigator-sponsored clinical trial with NeuVax™ (nelipepimut-S) in patients with Ductal Carcinoma in Situ (DCIS). The trial is being conducted in collaboration with the National Cancer Institute (NCI) and The University of Texas MD Anderson Cancer Center Phase I and II Chemoprevention Consortium. Little is known regarding the endogenous immune response to DCIS or the potential role of targeting DCIS with immunotherapy.  This study was developed to test the NeuVax vaccine in women with DCIS to determine whether antigen-specific immunity is induced and whether the induced immune response suppresses the growth of DCIS cells. Completion of this study will determine the safety and immunologic efficacy of vaccination with NeuVax in patients with DCIS of the breast. The trial will also provide the necessary data to determine whether a subsequent, larger phase 2 or 3 trial will be conducted. The primary endpoint will evaluate the effect of the NeuVax vaccine on NeuVax -specific cytotoxic T lymphocytes measured in the blood of patients with HLA-A2 positive DCIS. Secondary endpoints include evaluation of toxicity, In vivo immune response (delayed type hypersensitivity reaction (DTH)), epitope spreading, T-cell functional capacity, presence of DCIS at resection, and histologic immune response measured by degree of lymphocyte infiltration, proliferation, and apoptosis. Elements of the inclusion criteria include pre- or post-menopausal women 18 years of age and older with a diagnosis of DCIS made by core needle biopsy and an area of radiographic abnormality measuring at least one centimeter.  Trial participants must be HLA-A2 positive, have with an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 (Karnofsky ≥ 60%) and adequate kidney and liver function as measured by creatinine, bilirubin, and liver enzymes The study design will operate as follows.  Once the patient is identified, baseline testing and pre-study evaluation is done within thirty days prior to randomization.  Patients are then randomized to either the NeuVax plus GM-CSF treatment arm (n=32 randomized/27 evaluable) or the GM-CSF only control arm (n=16 randomized/13 evaluable).  Patients will receive three doses of the vaccine or control at Day 0, Day 14 ± 3 days, and Day 28 ± 3 days. Surgery to remove the DCIS is then performed at Day 35 ± 3 days and will include blood collection. DTH evaluations are done two to three days prior to and the day of the first dose.  The post surgery clinical visit also includes DTH evaluation, cardiac evaluation, and blood collection.  The final clinical visit with blood collection will take place 3 months ± 7 days post operation. The poster presentation from the conference will be available on Galena’s website here. Additional details including clinical trial locations can be found on the ClinicalTrials.gov site here.  The abstract can be found on the conference website here. The poster, entitled, “Determining the optimal vaccination strategy using a combination of the folate binding protein (FBP) peptide vaccine (E39+GM-CSF) and an attenuated version (E39') to maximize the immunologic response in breast cancer patients,” was presented on the breast cancer patients in the Company’s GALE-301 (E39) and GALE-302 (E39’) Phase 1b clinical trial targeting Folate Binding Protein. Dr. Bejadnik continued, “Due to lower folate binding protein expression and less aggressive chemotherapy regimens, breast cancer patients are more antigen naïve and have a less suppressed immune system, which may support the use of an attenuated version of the vaccine in these patients, as presented in the poster.  We continue to evaluate this program in both breast and ovarian cancer patients as we determine the best path forward for the assets.” In the trial, both the E39 and E39’ peptide vaccines were noted to be well tolerated and immunogenic with no clinicopathologic differences between groups. Local reaction increased in all groups with administration of the vaccine as measured and assessed using orthogonal means.  The greatest increase was seen in the treatment arm that administered GALE-301 followed by GALE-302, which approached statistical significance, and this arm was also the only arm with a statistically significant increase in DTH. While no difference was seen in E39-specific CTLs between groups, the in vivo response was enhanced with the use of E39’ after E39. This may indicate expansion of more effective clonal populations of CD8+ T cells with this strategy. These results may be specific to breast cancer patients who are relatively antigen-naïve with intact immune systems. Further analysis of these patients as this trial continues will determine the optimal vaccination strategy capable of stimulating and maintaining effective immunity to prevent breast cancer recurrence. Thirty-five HLA-A2-positive breast cancer patients were enrolled after completion of standard of care and without evidence of disease, with n=27 completing the primary vaccination series (PVS). The PVS includes six inoculations, one every 3-4 weeks containing 250mcg GM-CSF plus 500mcg peptide in the first five patients per arm and 250mcg GM-CSF + 1000mcg of peptide in the second five patients. To assess the in vivo immune response, local reaction was measured 48 hours after each inoculation, and delayed type hypersensitivity (DTH) was measured pre-PVS, and at one and six months post-PVS. The poster presentation from the conference will be available on Galena’s website here. The abstract can be found on the conference website here. NeuVax™ (nelipepimut-S) is a first-in-class, HER2-directed cancer immunotherapy under evaluation to prevent breast cancer recurrence after standard of care treatment in the adjuvant setting.  It is the immunodominant peptide derived from the extracellular domain of the HER2 protein, a well-established target for therapeutic intervention in breast carcinoma. The nelipepimut-S sequence stimulates specific CD8+ cytotoxic T lymphocytes (CTLs) following binding to specific HLA molecules on antigen presenting cells (APC). These activated specific CTLs recognize, neutralize and destroy, through cell lysis, HER2 expressing cancer cells, including occult cancer cells and micrometastatic foci. The nelipepimut-S immune response can also generate CTLs to other immunogenic peptides through inter- and intra-antigenic epitope spreading.   In clinical studies, NeuVax is combined with recombinant granulocyte macrophage-colony stimulating factor (GM-CSF). NeuVax is currently in two breast cancer studies in combination with trastuzumab (Herceptin®; Genentech/Roche): a Phase 2b trial in node positive and triple negative HER2 IHC 1+/2+ (clinicaltrials.gov identifier: NCT01570036); and, a Phase 2 trial in high risk, node positive or negative HER2 IHC 3+ patients (clinicaltrials.gov identifier: NCT02297698).  Phase 2 clinical trials with NeuVax are also planned in patients with ductal carcinoma in situ (DCIS), and in patients with gastric cancer. Ductal Carcinoma in Situ (DUK-tul KAR-sih-NOH-muh in SY-too), or DCIS, is defined by the NCI as a noninvasive condition in which abnormal cells are found in the lining of a breast duct, and is the most common type of breast cancer.  The abnormal cells have not spread outside the duct to other tissues in the breast.  In some cases, DCIS may become invasive cancer and spread to other tissues; currently there is no way to know which lesions could become invasive.  Current treatment options for DCIS include breast-conserving surgery and radiation therapy with or without tamoxifen, breast-conserving surgery without radiation therapy, or total mastectomy with or without tamoxifen.  According to the American Cancer Society, in 2015 there were over 60,000 diagnoses of ductal carcinoma in situ. GALE-301 and GALE-302 are cancer immunotherapies that consist of a peptide derived from Folate Binding Protein (FBP) combined with the immune adjuvant, granulocyte macrophage-colony stimulating factor (GM-CSF) for the prevention of cancer recurrence in the adjuvant setting.  GALE-301 is the E39 peptide, while GALE-302 is an attenuated version of this peptide, known as E39’.  FBP is a well-validated therapeutic target that is highly over-expressed in ovarian, endometrial and breast cancers, and is the source of immunogenic peptides that can stimulate cytotoxic T lymphocytes (CTLs) to recognize and destroy FBP-expressing cancer cells. Two trials are ongoing with FBP peptides: the GALE-301 Phase 2a portion of the Phase 1/2a clinical trial is ongoing in ovarian and endometrial adenocarcinomas (ClinicalTrials.gov Identifier: NCT01580696); the GALE-301 plus GALE-302 Phase 1b clinical trial is ongoing in breast and ovarian cancers (ClinicalTrials.gov Identifier: NCT02019524). New cases of breast cancer occur at an annual rate of 125 per 100,000 women in the U.S., with an estimated 246,660 new cases and 40,450 deaths in 2016. Approximately 89.7% of breast cancer patients are expected to survive five years after diagnosis. Approximately 12.4% of women will be diagnosed with breast cancer at some point during their lifetime (2011 – 2013 data).  The prevalence data from 2013 showed an estimated 3,053,450 women living with breast cancer in the United States. Galena Biopharma, Inc. is a biopharmaceutical company committed to the development and commercialization of hematology and oncology therapeutics that address unmet medical needs. Galena’s pipeline consists of multiple mid-to-late-stage clinical assets led by its hematology asset, GALE-401, and novel cancer immunotherapy programs including NeuVax™ (nelipepimut-S) and GALE-301/GALE-302. For more information, visit www.galenabiopharma.com. This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995.  Such statements include, but are not limited to, statements about the progress of the development of Galena’s product candidates, patient enrollment in our clinical trials, as well as other statements related to the progress and timing of our development activities, present or future licensing, collaborative or financing arrangements, expected outcomes with regulatory agencies, and projected market opportunities for product candidates or that otherwise relate to future periods. These forward-looking statements are subject to a number of risks, uncertainties and assumptions, including those identified under “Risk Factors” in Galena’s Annual Report on Form 10-K for the year ended December 31, 2015 and most recent Quarterly Reports on Form 10-Q filed with the SEC. Actual results may differ materially from those contemplated by these forward-looking statements. Galena does not undertake to update any of these forward-looking statements to reflect a change in its views or events or circumstances that occur after the date of this press release. NeuVax is a trademark of Galena Biopharma, Inc.


BEERSE, Belgium--(BUSINESS WIRE)--Janssen-Cilag International NV today announced the publication of data revealing radiographic progression-free survival (rPFS) of 16.5 months (95% CI, 13.5–20.0) and treatment duration of 11.6 months (95% CI, 10.2–12.8) in men treated with ZYTIGA® (abiraterone acetate) plus prednisone (AAP), in the real-world, outside the clinical trial setting. The study assessed men being treated for asymptomatic and mildly symptomatic metastatic castration-resistant prostate cancer (mCRPC), following androgen deprivation therapy (ADT).1 These valuable insights were shown despite the real-world study population including those who had a poor prognosis or were difficult-to-treat patients, usually excluded from clinical trials. These data are part of a comprehensive real-world evidence (RWE) portfolio being presented by Janssen at this year’s American Society of Clinical Oncology Genitourinary Cancers Symposium (ASCO GU) in Orlando, Florida. “Real-world evidence research is key in patient-focused clinical practice, as it helps physicians to better address patient needs. It complements data obtained from clinical trials to provide greater understanding of treatment outcomes, disease management and impact on quality of life in broad patient populations, including those with comorbidities,” said Dr Martin Boegemann, Department of Urology, Muenster University Medical Center, Muenster, Germany. ”It is helpful to see new data for treatment outcomes in real world patients confirm those seen in a clinical trial setting. These new findings add to the growing bank of real-world evidence available across Europe, which is becoming more and more important in helping us choose the best treatments to transform patient outcomes.” Patients in the pivotal COU–AA–302 trial reached a median duration of treatment of 13.8 months (IQR, 8.3–27.4) and a median rPFS of 16.5 months (95% CI, 13.8–16.8).1,2,3,4 Results were similar across both settings, despite almost 10% of patients in the RWE study having visceral metastases (metastases to internal organs i.e. the liver and/or lungs) and/or an Eastern Cooperative Oncology Group (ECOG) performance status of 2-3 (those unable to carry out work, but still capable or partially capable of self-care).1 These patients were not included in the COU-AA-302 study.4 Further to this, additional findings from The Prostate Cancer Registry, Europe’s first and largest prospective RWE study in mCRPC are being presented at ASCO GU.5 The Prostate Cancer Registry was initiated in 2013, as a long-term commitment by Janssen to address optimal treatment of mCRPC in routine practice in the real world. It has enrolled over 3,000 mCRPC patients in 199 centres across 16 European countries.5 Dr Ivo Winiger-Candolfi, Oncology Therapeutic Area Lead, Janssen Europe, the Middle East and Africa (EMEA) said: “Real-world evidence is extremely valuable in offering findings that complement clinical trials and provide significant insights into the performance and the use of a drug in real-world medical settings which will ultimately translate into how to best treat patients. This is particularly evident in prostate cancer, as it is the most common cancer in men and has a diverse patient population with varying treatment needs. Janssen is continuing to support real-world evidence research to help transform patient outcomes, with the aim of making cancer a more manageable condition in the future.” Prostate cancer is the most commonly diagnosed cancer in men, with over 400,000 new cases diagnosed in Europe each year.6 Latest prostate cancer figures show that there are currently three million men living with the disease in Europe.7 About the Boegemann et al. study The Boegemann et al. study is a retrospective chart review of 224 asymptomatic and mildly symptomatic post-ADT mCRPC patients treated with ZYTIGA (abiraterone acetate) plus prednisone (AAP) from 18 centres across Belgium, Germany and the UK.1 The real-world study included patients with visceral metastases (metastases to internal organs i.e. the liver and/or lungs) (9.8%) and those with an Eastern Cooperative Oncology Group (ECOG) performance status of 2-3 (those unable to carry out work, but still capable or partially capable of self-care) (9.4%) (patients usually excluded from the clinical trial setting).1 The Prostate Cancer Registry was initiated in 2013 as a long-term commitment by Janssen to address optimal treatment of mCRPC in routine practice. The Registry was designed in consultation with specialists in mCRPC and examines patients being managed in a range of oncology and urology settings, with the aim of reflecting routine clinical practice. 8 Patients are enrolled upon initiating a treatment for mCRPC or a period of surveillance, defined as not currently receiving an active treatment for castration resistance. The Registry is prospectively collecting data on a pan-European scale on patient demography and status, treatment sequencing and effectiveness, ongoing disease management, quality of life, medical resource utilisation and outcomes.8 The first analysis was presented at the 2015 European Cancer Congress (ECC) in Vienna, Austria and further data will be published regularly over the coming years.8 The latest Prostate Cancer Registry animation can be viewed here. ZYTIGA is the only approved therapy in mCRPC that inhibits production of androgens (which fuel prostate cancer growth) at all three sources that are important in prostate cancer - the testes, adrenals and the tumour itself.9,10,11 ZYTIGA has been approved in more than 90 countries and to date, has been prescribed to more than 269,500 men worldwide.12,13 In 2011, ZYTIGA in combination with prednisone/prednisolone was approved by the European Commission (EC) for the treatment of metastatic castration-resistant prostate cancer (mCRPC) in adult men whose disease has progressed on or after a docetaxel-based chemotherapy regimen. In December 2012, the EC granted an extension of the indication for ZYTIGA permitting its use, in combination with prednisone or prednisolone, for the treatment of mCRPC, in adult men who are asymptomatic or mildly symptomatic after failure of androgen deprivation therapy in whom chemotherapy is not yet clinically indicated.9 The most common adverse events seen with abiraterone acetate include urinary tract infection, hypokalaemia, hypertension, peripheral oedema and diarrhoea. For a full list of side effects and for further information on dosage and administration, contraindications and other precautions when using ZYTIGA, please refer to the summary of product characteristics, which is available at: http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/002321/WC500112858.pdf At the Janssen Pharmaceutical Companies of Johnson & Johnson, we are working to create a world without disease. Transforming lives by finding new and better ways to prevent, intercept, treat and cure disease inspires us. We bring together the best minds and pursue the most promising science. We are Janssen. We collaborate with the world for the health of everyone in it. Learn more at www.janssen.com/emea. Follow us on http://www.twitter.com/janssenEMEA for our latest news. Cilag GmbH International; Janssen Biotech, Inc.; and Janssen-Cilag International NV are part of the Janssen Pharmaceutical Companies of Johnson & Johnson. 1 Boegemann et al. Real-World Treatment with Abiraterone Acetate in Chemotherapy-Naïve Metastatic Castration-Resistant Prostate Cancer Patients. Poster presented at the American Society of Clinical Oncology Genitourinary Symposium 2017, February 16-18, Orlando, Florida, USA. Poster presentation. ASCO GU abstract #239. Last accessed February 2017. 2 Rathkopf et al. Updated Interim Efficacy Analysis and Long-term Safety of Abiraterone Acetate in Metastatic Castration-resistant Prostate Cancer Patients Without Prior Chemotherapy (COU-AA-302). EUROPEAN UROLOGY 2014; 66: 815-825. Last accessed February 2017. 3 Ryan CJ, Smith MR, de Bono JS, et al. Abiraterone in Metastatic Prostate Cancer without Previous Chemotherapy. N Engl J Med. 2013 Jan; 368(2): 138 - 48. 4 Ryan C.J et al. Abiraterone acetate plus prednisone versus placebo plus prednisone in chemotherapy-naive men with metastatic castration-resistant prostate cancer (COU-AA-302): final overall survival analysis of a randomised, double-blind, placebo-controlled phase 3 study. The Lancet Oncology. 2015; 16, 2: p152-160. Available at: http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(14)71205-7/abstract. Last accessed February 2017. 5 Chowdhury S et al. The Prostate Cancer Registry: Real-World outcomes in first-line treatment of metastatic castration-resistant prostate cancer (mCRPC). Poster presented at the American Society of Clinical Oncology Genitourinary Symposium 2017, February 16-18, Orlando, Florida. Poster presentation. ASCO GU abstract #212. Last accessed February 2017. 6 Ferlay J et al. Cancer incidence and mortality patterns in Europe: Estimates for 40 countries in 2012. European Journal of Cancer. 2013; 49: p1374–1403. Last accessed February 2017. 7 European Commission. CORDIS Express: Prevention, diagnosis and treatment of prostate cancer. Available at: http://cordis.europa.eu/news/rcn/122705_en.html. Last accessed February 2017. 8 Chowdhury S et al. The Prostate Cancer Registry: First Results from an International, Prospective, Observational Study of Men with Metastatic Castration- Resistant Prostate Cancer (mCRPC). Poster presented at the European Cancer Congress 2015, September 25-29, Vienna, Austria. Poster Presentation. ECC abstract #2548. Available at: https://www.europeancancercongress.org/Scientific-Programme/Abstract-search?abstractid=21001. Last accessed February 2017. 9 ZYTIGA® summary of product characteristics (February 2017). Available at: http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/002321/WC500112858.pdf. Last accessed February 2017. 10 Hoy, SM. et al. Abiraterone Acetate: A review of its use in patients with metastatic castration-resistant prostate cancer drugs. Drugs 2013; 73:2077-2091. Last accessed February 2017. 11 Ritch, CR. Cookson, MS. Advances in the management of castration resistant prostate cancer. BMJ. 2016 Oct 17;355:i4405. Doi: 10.1136/bmj.i4405. Last accessed February 2017 12 Ye,D. A phase 3, double-blind, randomized placebo-controlled efficacy and safety study of abiraterone acetate in chemotherapy-naïve patients with mCRPC in China, Malaysia, Thailand and Russia. Asian Journal of Urology. 2017.Doi.org/10.1016/j.ajur.2017.01.002. Last accessed February 2017 13 Zytiga asset portal. Available at: https://janssenassetexchange.com/Zytiga/Home.aspx. Last accessed February 2017


Freidlin B.,U.S. National Cancer Institute | Korn E.L.,U.S. National Cancer Institute | Gray R.,Eastern Cooperative Oncology Group
Clinical Trials | Year: 2010

Background The ultimate goal of a phase III randomized clinical trial designed to demonstrate superiority of a new versus standard therapy is to provide sufficiently compelling evidence to affect clinical practice. To balance patient interests against the need for acquiring evidence it is desirable to stop a study for inefficacy as soon as convincing evidence that the new therapy is not beneficial becomes available. Purpose To discuss potential deficiencies in some commonly used inefficacy monitoring rules and to propose a comprehensive inefficacy monitoring procedure. Methods The proposed approach is developed using clinical, logistical, and statistical considerations. The new approach is compared to the commonly used inefficacy rules in a simulation study. Results Some of the commonly used inefficacy rules are suboptimal with respect to the strength of evidence required for stopping throughout the trial: too conservative in the middle and/or too aggressive at the end. Our approach allows timely stopping (a) if the new therapy is harmful, and (b) if the interim data provides convincing evidence that the new therapy has no tangible benefit. Relative to common inefficacy rules, our procedure is shown to result in potentially fewer treated patients and shorter study duration under the null hypothesis with only a minor loss of power under the alternative hypothesis. Limitations The proposed procedure is applicable to superiority designs with well-defined clinical objectives. Conclusions The proposed inefficacy approach is attractive from statistical, clinical, and logistical standpoints. By decreasing average stopping times relative to the commonly used boundaries, our rule lessens patient exposure to inactive treatments, improves resource utilization, and accelerates dissemination of important clinical information. At the same time, the proposed rule provides a clear benchmark for providing compelling evidence that the new therapy is not beneficial. © 2010 The Author(s).


Gupta V.,Princess Margaret Hospital | Richards S.,University of Oxford | Rowe J.,Eastern Cooperative Oncology Group
Blood | Year: 2013

Hematopoietic cell transplantation (HCT) and prolonged chemotherapy are standard postremission strategies for adult acute lymphoblastic leukemia in first complete remission, but the optimal strategy remains controversial. There are no randomized trials of allogeneic HCT. In the present study, updated individual patient data were collected and analyzed from studies with information on availability of matched sibling donor (used to mimic randomization) and from randomized trials of autograft versus chemotherapy. Data from 13 studies including 2962 patients, excluding Philadelphia chromosome-positive patients, showed a survival benefit for having a matched sibling donor for patients < 35 years of age (OR = 0.79; 95% CI, 0.70-0.90, P = .0003) but not for those ≥ 35 years of age (OR = 1.01; 95% CI, 0.85-1.19, P = .9; heterogeneity P = .03) because of the higher absolute risk of nonrelapse mortality for older patients. No differences were seen by risk group. There was a trend toward inferior survival for autograft versus chemotherapy (OR = 1.18; 95% CI, 0.99-1.41; P = .06). No beneficial effect of autografting was seen compared with chemotherapy in this analysis. We conclude that matched sibling donor myeloablative HCT improves survival only for younger patients, with an absolute benefit of approximately 10% at 5 years. Improved chemotherapy outcomes and reduced nonrelapse mortality associated with allogeneic HCT may change the relative effects of these treatments in the future. © 2013 by The American Society of Hematology.

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