Différents essais de phase III marquent ce Congrès 2014 de l’American Society of Clinical Oncology (ASCO) au point de confirmer l’efficacité de certaines grandes options thérapeutiques, déjà fréquemment mises en œuvre et d’établir de nouvelles normes de soins. 4 de ces études, soutenues par les NIH et présentées en session plénière font ainsi référence, en raison de leur très larges implications cliniques.
Car ces études portent déjà sur les 3 premiers cancers en terme d’incidence, les cancers du sein de la prostate et colorectal. Ensuite, elles révèlent "les bonnes" options pour optimiser les thérapies habituelles, chimiothérapie, traitements hormonaux, et traitements personnalisés et tranchent aussi la question, en particulier pour le cancer colorectal avancé. » Grâce ces études « , explique le Dr Clifford A. Hudis, président de l’ASCO, » les patients vivront mieux et plus longtemps « .
Cancer du sein hormonosensible: Cette étude montre que l’inhibiteur de l’aromatase (exémestane) plus suppression ovarienne réduit de 28 % le risque de tout type de cancer invasif, et réduit de 34 % le risque de récidive de cancer invasif du sein, vs tamoxifène plus suppression ovarienne. 5 ans après le début de l’étude, 92,8 % des femmes traitées par exémestane plus suppression ovarienne ne présentent pas de récidive de cancer du sein (vs 88,8 % par tamoxifène plus suppression ovarienne).
Alors que durant des années, le tamoxifène a été le traitement hormonal standard pour la prévention des récidives de cancer du sein chez les jeunes femmes hormono-dépendantes, ces résultats confirment la supériorité de l’alternative avec l’exémestane.
Cancer de la prostate hormono-sensible : L’adjonction du docétaxel au traitement hormonal initial améliore considérablement la survie chez les hommes atteints de métastases du cancer de la prostate hormono-sensible. Des données qui suggèrent l’inclusion du docétaxel en traitement de première ligne pour les hommes ayant une maladie avancée qui sont en assez bonne santé pour la chimiothérapie, en particulier avec un cancer diffus. L’ajout du docétaxel permet, dans cette étude, d’allonger de 17 mois la survie médiane et de retarder la progression de la maladie. Ainsi, le délai médian jusqu’à progression clinique est de 19,8 mois dans le groupe traitement hormonal seul vs 32,7 mois dans le groupe » plus docétaxel.
Cancer colorectal métastatique : Bevacizumab plus chimiothérapie et cetuximab plus chimiothérapie offrent des avantages de survie similaires pour les patients atteints de cancer colorectal métastatique, avec une survie médiane de 29 mois pour chaque option. Les conclusions suggèrent également 2 chimiothérapies possibles en combinaison avec l’un des deux médicaments.
Cancer du sein HER2-positif : Cette large étude de phase III suggère que, post-chirurgie, un traitement par combinaison de deux médicaments ciblés HER2 (trastuzumab et lapatinib) n’est pas plus efficace que le traitement standard par trastuzumab seul pour les femmes atteintes d’un cancer du sein HER2-positif. Les chercheurs ne constatent aucune différence statistiquement significative entre les groupes de traitement dans la survie sans maladie à 4 ans, (qui atteint entre 86 et 88%).
Bref, des résultats majeurs qui peuvent rassurer et orienter les médecins et les patients qui hésitent sur le choix du traitement.
· A landmark study that was a joint analysis of two phase III trials, TEXT and SOFT, demonstrated that the aromatase inhibitor exemestane more effectively prevents breast cancer recurrences than tamoxifen, when given with ovarian function suppression (OFS), in premenopausal women with hormone-sensitive cancers. In the study, exemestane plus OFS reduced the relative risk of women developing a subsequent invasive cancer by 28 percent, and specifically reduced the relative risk of breast cancer recurrence by 34 percent, compared with tamoxifen plus OFS.
· “For years, tamoxifen has been the standard hormone therapy for preventing breast cancer recurrences in young women with hormone-sensitive disease. These results confirm that exemestane with ovarian function suppression constitutes a valid alternative,” said lead study author Olivia Pagani, MD, clinical director of the Breast Unit at the Oncology Institute of Southern Switzerland in Bellinzona, Switzerland. “Our findings indicate that exemestane is better than tamoxifen, when given with ovarian function suppression, but longer follow up of these young women will be important to assess survival, and any long-term side effects and fertility.”
· The TEXT and SOFT trials were led by the International Breast Cancer Study Group (IBCSG) in collaboration with the Breast International Group (BIG) and the North American Breast Cancer Group (NABCG) as a successful, worldwide collaboration spanning 27 countries and six continents. The trials were partially funded by the U.S. National Cancer Institute.
· The joint analysis of TEXT and SOFT is the largest study worldwide evaluating adjuvant aromatase inhibitor therapy with OFS in young women with breast cancer, and the first to demonstrate the value of such therapy in women with hormone receptor-positive cancer. Aromatase inhibitors have primarily been used in postmenopausal women, because their use requires that women have a low level of estrogen. In the TEXT and SOFT trials, ovarian function suppression was used in premenopausal women to emulate the low estrogen levels that naturally occur in menopause.
· The standard adjuvant endocrine (hormone) therapy for premenopausal women is currently five years of tamoxifen. In some countries, physicians recommend adding OFS to tamoxifen in high-risk younger women. This approach is less common in the United States as the benefit of adding OFS to tamoxifen is uncertain. The SOFT trial also addresses the impact of adding OFS to tamoxifen, and the results will be available in late 2014. The joint analysis of the TEXT and SOFT trials studied the outcomes of 4,690 women, whose average age was 43 years, who were randomized to receive exemestane plus OFS or tamoxifen plus OFS for five years. OFS was achieved through treatment with the drug triptorelin, surgical oophorectomy, or ovarian irradiation. Some women also received adjuvant chemotherapy, as decided with their physician.
· The cancer-free survival at five years was 91.1 percent in the exemestane plus OFS group, versus 87.3 percent in the tamoxifen plus OFS group, which was a 28 percent relative reduction in risk. There was a 34 percent relative reduction in breast cancer recurrence risk in the exemestane plus OFS group compared to the tamoxifen plus OFS group and a 22 percent relative reduction in distant recurrence (metastasis) risk. The five-year overall survival rates were high in both groups ─ 95.9 percent in the exemestane plus OFS group and 96.9 percent in the tamoxifen plus OFS group. Longer follow-up is needed to accurately assess the impact of the two treatments on long-term survival.
· The side effects were similar to those reported in previous studies comparing adjuvant aromatase inhibitors and tamoxifen in postmenopausal women, and differed depending on the agent. Despite the side effects, only 14 percent of TEXT and SOFT participants completely stopped the protocol-assigned treatments early – an adherence rate that is higher than what is seen in everyday practice. Dr. Pagani stated that this high compliance rate is important information for doctors who wish to propose this treatment to their patients.
· The TEXT and SOFT trials were conducted at the same time and in the same general population – premenopausal women with hormone receptor-positive early breast cancer. The original plan was to analyze each trial separately as well as jointly, given the common treatment groups of exemestane plus OFS and tamoxifen plus OFS in both trials. However, by combining the trials in a joint analysis, the results could be presented earlier, giving physicians and patients the possible benefit of acting on the results sooner.
· This research was supported in part by Pfizer, Ipsen, the International Breast Cancer Study Group, and the National Cancer Institute, National Institutes of Health.
· ASCO Perspective:
“Young women with breast cancer have long needed additional treatment options after surgery, and now they may have one,” said ASCO president Clifford A. Hudis, MD, FACP. “Tamoxifen has been a gold standard for decades and has significant benefits. Now, with ovarian suppression, aromatase inhibitors are an option offering a further reduction in the risk of recurrence.”
· Summary contains updated data not included in the abstract
· Findings from a federally funded phase III study, E3805, indicate that adding the chemotherapy drug docetaxel to standard hormone therapy extends survival for men with newly diagnosed hormone-sensitive prostate cancer by roughly 13 months. The survival benefit is even greater for the subset of men with extensive disease spread (high-extent disease).
· “Hormone therapy has been a standard treatment for prostate cancer since the 1950s,” said lead study author Christopher Sweeney, MBBS, medical oncologist at the Lank Center of Genitourinary Oncology at the Dana-Farber Cancer Institute in Boston, MA. “This is the first study to identify a strategy that prolongs survival in newly diagnosed metastatic prostate cancer. The benefit is substantial and warrants this being a new standard treatment for men who have high-extent disease and are fit for chemotherapy.”
· Androgen hormones fuel prostate cancer growth. Hormonal therapy – also called androgen deprivation therapy (ADT) – alone is the standard first-line treatment for hormone-sensitive prostate cancer. Although ADT is effective, the disease eventually becomes resistant to the therapy in most patients. About 30,000 patients die of hormone-resistant prostate cancer in the United States every year. Chemotherapy is typically initiated only after the disease progresses despite ADT.
· In this National Cancer Institute-led study, 790 men with newly diagnosed metastatic prostate cancer were randomly assigned to receive either ADT alone or ADT with docetaxel over a period of 18 weeks. Approximately two-thirds of patients had high-extent disease, meaning that the cancer had spread to major organs and/or the patient had bone metastases. When the disease worsened, 45 patients in the ADT plus docetaxel group received additional docetaxel. In the ADT only group, 123 patients received docetaxel at disease progression.
· At a median follow-up of 29 months, there were 136 deaths in the ADT-alone group vs. 101 in the ADT plus docetaxel group. The median overall survival was 44 months in the ADT group and 57.6 months in the ADT plus docetaxel group. The relative improvement in median overall survival was even larger among the 520 patients with high-extent disease (32.2 months vs. 49.2 months). The median overall survival for the subset with low-extent disease takes longer to reach as these patients respond better to ADT, and the median survival has not yet been reached.
· Docetaxel also delayed disease progression, assessed by either PSA rise or appearance of new metastases or symptom worsening. At one year, the proportion of patients with PSA levels less than 0.2 ng/mL (a PSA level of less than 0.2 is considered a sign of a better remission) was 11.7 percent in the ADT group vs. 22.7 percent in the ADT plus docetaxel group. The median time to clinical progression (new symptoms or metastases detected on a scan) was 19.8 months in the ADT group vs. 32.7 months in the ADT plus docetaxel group.
· This new treatment paradigm will entail earlier, multidisciplinary care involving the collaboration of both urologists and oncologists, who both commonly treat men with prostate cancer, Dr. Sweeney said. Follow-up of patients will continue to assess survival benefits for patients with low-extent disease. Quality-of-life data from this study will be analyzed and reported at a later time.
· This research was supported by the National Cancer Institute, National Institutes of Health.
· ASCO Perspective:
· Results from a large federally funded phase III study demonstrate that four common first-line treatment regimens – bevacizumab plus chemotherapy and cetuximab plus chemotherapy – are equally effective for patients with metastatic colorectal cancer and no KRAS mutations. In the study, the median overall survival was roughly 29 months with either approach. The data also suggest that either FOLFOX (oxaliplatin/5-fluorouracil/leucovorin) or FOLFIRI (irinotecan/5-fluorouracil/leucovorin) chemotherapy regimens are acceptable in combination with either of the two targeted drugs.
· “About 75 percent of patients with metastatic colorectal cancer in the United States initially receive bevacizumab-based therapy, although we know that cetuximab-based therapy is also a good option for a subset of patients,” said lead author Alan P. Venook, MD, the Madden Family Distinguished Professor of Medical Oncology and Translational Research at the University of California in San Francisco, CA. “Our findings clearly show that the two antibodies – with either FOLFOX or FOLFIRI – are both acceptable, and similarly effective. This should reassure doctors and patients facing decisions about treatment selection.”
· Each year, about 50,000 Americans are diagnosed with metastatic colorectal cancer. Targeted therapies have played a key part in extending survival, from 10 months 20 years ago to the nearly 2.5 years seen in this study. Bevacizumab targets VEGF, blocking the development of blood vessels that tumors need to grow, while cetuximab targets EGFR, a protein involved in cancer growth and spread. Bevacizumab with FOLFOX is widely used in the United States, while cetuximab-based regimens tend to be used more frequently in Europe.
· In the study, 1,137 patients with untreated metastatic colorectal cancer were randomly assigned to receive bevacizumab plus chemotherapy or cetuximab plus chemotherapy. The selection of chemotherapy was based on physician preference (26.6 percent received FOLFIRI, 73.4 percent FOLFOX). The median follow-up was 24 months.
· There were no significant differences in either overall or progression-free survival between the treatment groups. In the bevacizumab plus chemotherapy group, the overall and progression-free survival were 29 months and 10.8 months, respectively, and 29.9 months and 10.4 months respectively in the cetuximab plus chemotherapy group.
· No new treatment side effects were detected in this study. Common side effects of bevacizumab are high blood pressure, headache, mouth sores, nosebleed, diarrhea, bleeding from the rectum, loss of appetite, fatigue, and weakness, and the most common side effects of cetuximab are acne-like rash, itching, changes in fingernails and toenails, infections, fatigue, and low blood electrolyte levels. Costs of bevacizumab and cetuximab are comparable but side effects are slightly different. FOLFIRI and FOLFOX also differ in side effects ─ FOLIFIRI causes more hair loss and diarrhea but FOLFOX causes neuropathy that often necessitates stopping treatment. Updated analyses show that the overall quality of life for patients on either of the antibodies is similar.
· Dr. Venook remarked that this kind of head-to-head comparative clinical trial comparing two agents from different companies with similar indications probably would not have been possible without the nation’s investment in clinical trials led by the National Cancer Institute. “This study shows that we are still doing good, important work, even in the era of reduced funding for cooperative groups,” he said.
· Forthcoming analyses from this study will explore benefits of these approaches in different subsets of patients. Genomic profiling will be conducted to identify potential prognostic markers, which might be helpful in selecting optimal treatments for individual patients in the future.
· This research was supported in part by the National Cancer Institute, National Institutes of Health; Imclone; Roche; Genentech; BMS; and Eli Lilly.
· ASCO Perspective:
“With this finding, oncologists and patients have more ways to personalize cancer treatment,” said ASCO president Clifford A. Hudis, MD, FACP. “They can be reassured that two widely used regimens offer good and equivalent survival.”