Especially for metastatic HER2-low neoplasms, an innovative drug doubles disease-free survival. But there are several other advances as well
The main news emerging from the annual congress ofAmerican Society of Clinical Oncology (Asco)underway in Chicago, concern the breast cancer. In fact, at the 2022 edition of the appointment that brings together the major specialists in oncology, several relevant studies are presented for what, with 55 thousand new diagnoses every yearthe most common cancer not only in women, but in the entire Italian population.
One in eight women will get sick in their lifetime and it is good to remember that males can also develop it, although it is a very rare event. Saverio Cinieri, president of the Italian Medical Oncology Association (Aiom) -. Thanks to the successes in early diagnosis and new therapies, today 87% of patients live 5 years after diagnosis, but above all against the more aggressive forms and those that have reached the metastatic stage, we need innovative strategies to extend the life of patients. or to increase the number of healings.
Many different subtypes: 37 thousand metastatic patients in Italy
For this reason, scientific research continues, based on a fundamental premise: today we know that there are many different types of breast cancer and It is essential to know which histological and molecular subtype you are dealing with to be able to choose, among the many therapies available, the most effective one according to the individual case.
Today, in Italy, more than 834 thousand women live after being diagnosed with breast cancer: some are cured, others are being treated, about 37 thousand are living with a metastatic form – he says. Giuseppe Curigliano, director of the Division for the development of New Drugs and Innovative Therapies of the European Institute of Oncology in Milan -. We have learned to distinguish the most indolent forms, those with less risk of relapse (so much so that in some cases we can spare the patients chemotherapy and its side effects) and conducted many studies to try to better understand the evolution of the disease, the reasons for it. the basis of the risk of relapse and metastasis even after 15 or 20 years from the first breast cancer, the characteristics of the various subtypes of cancer, with the aim of optimizing the treatment of each woman to obtain the best possible result with the least toxicity .
Important advances for metastatic HER2-low tumors
This premise is necessary to understand the importance of the study presented in the plenary session of the Asco 2022 conference, the one reserved for the most important innovations: the phase 3 trial DESTINY Breast 04 compared 557 patients with an inoperable HER2-low carcinoma or metastatic standard chemotherapy with the conjugated antibody trastuzumab deruxtecan, specifically engineered to target the HER2 receptor.
That of HER2-positive one of the three main types of breast cancer (together with tumors with expression of estrogen / progesterone receptors and triple negative tumors) – explains Cinieri, director of the Medical Oncology and Breast Unit of the Perrino Hospital in Brindisi – . Due to its considerable aggressiveness, up to the 1990s this type of cancer was a harbinger of very poor prognosis., then came several effective drugs, including trastuzumab and its version “combined” with deruxtecan, which is already in use for both breast and gastric cancer (always HER2-positive). THE HER2-low tumors they represent all tumors that do not have high expression or amplification of the HER2 receptor: in practice over half of the 55 thousand new cases diagnosed annually in our country. The outcomes of this trial are bound to change clinical practice.
The current standard of care
The current standard of care for HER2-low patients chemotherapybut the results of this study change that because they show that using trastuzumab deruxtecan it is possible to keep the neoplasm under control for a longer time: compared to standard care, the time free from disease progression doubles (the time during which the tumor remains stable, from 5 to 10 months), also improving survival (from 17.5 months to 24) and quality of life, given that there are fewer side effects – underlines Curigliano, professor of Medical Oncology at the University of Milan -. An advantage that was demonstrated by the trial both in endocrine-responsive tumors and in so-called triple negative tumors. Not only. These results anticipate those of the DESTINY 06 study, which is exploring the role of trastuzumab deruxtecan in patients who have never received chemotherapy and who also have ultra-low HER2 (not identifiable in immunohistochemistry).
Italian research evaluating women with treatment-resistant cancer
Still in the direction of precision medicine another goes research, entirely conducted in our country (BioItaLEE), involving 287 patients with advanced or metastatic breast cancer hormone receptor positive and human epidermal growth factor receptor 2 negative (HR + / HER2-) recruited in 47 Italian centers. Over 37,000 women live with the diagnosis of metastatic disease, which in about 70% of cases expresses hormone receptors – he says Michelino De Laurentiiscoordinator of the study and director of the Department of Breast and Thoraco-Pulmonary Oncology at the National Cancer Institute Irccs Pascale Foundation of Naples -. The standard treatment for these neoplasms the combination of a cyclin inhibitor with hormone treatment. Participants were given the combination of ribociclib (cyclin inhibitor) plus letrozole (hormone therapy)
and 15 days after the start of the treatment we took a blood sample that looks for specific tumor markers to understand which women are most likely to respond to treatment and which are not, so that we can be more effective. With half of the patients living over 5 years we can say that we have made great progress: we are moving towards the chronicization of metastatic disease, an important goal.
Ribociclib has shown an advantage in overall survival in pre / peri and postmenopausal women, with different hormonal combinations. The BioItaLEE data are not yet definitive, but the effectiveness already demonstrated in the MONALEESA-2 study seems to be confirmed, – adds Grace Arpino, professor of Medical Oncology at the Federico II University of Naples, who presents the study at the Asco congress -. These results not only allow us to understand who is least likely to benefit from this curebut we are also investigating the mechanisms that lead to the resistance of the neoplasm and thus opting (after only 15 days from the start of treatment) for different treatments.
Positive hormone receptors
The TROPiCS-02 trial (also in phase three, the last one before final drug approval) recruited 543 advanced patients with a hormone receptor positive carcinoma (the so-called endocrine-responsive, HR + / HER2-), which represent 70% of breast cancers diagnosed each year.
The therapeutic strategy for these neoplasms consists ofhormone therapyused in several lines before coming to chemotherapy, which is less tolerated and cannot be administered for long periods – explains Giampaolo Bianchini, head of the Breast Group in the Oncology Department of the IRCSS San Raffaele Hospital -. Based on the results of this study, we know we have another effective weapon – sacituzumab govitecan an anti-TROP2 conjugated antibody, an extremely innovative drug that exploits the ability of an antibody capable of target a specific target on cancer cells, taking a potent chemotherapy with him. This allows on the one hand a great therapeutic efficacy, on the other hand to reduce the toxicity linked to the exposure of normal cells. A drug already proven useful against triple negative neoplasms (particularly aggressive subtype), which according to the results illustrated to Asco brings a statistically significant advantage in disease control time even in heavily pretreated patients with hormone receptor positive carcinoma.
From this Asco conference it is therefore clear that conjugated antibodies are “smart chemotherapy” – Curigliano concludes -: they work both in those who express the specific receptor and in those who do not express it, with fewer side effects and greater effectiveness in reaching the target of conventional chemo. In short, they can be widely used in many different types of breast cancers.
June 5, 2022 (change June 5, 2022 | 14:09)
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