IMMUNOTHERAPIES, targeted therapies, new endocrine therapies and conjugated antibodies: research in oncology, despite the pandemic, continues to give important results for the main big killers, and many will soon be transferred to clinical practice. What will be the main news for breast, prostate, lung, colorectal and melanoma cancers in this 2022? We asked five oncologists.
For breast cancer
Clinical research in the field of breast cancer has always been at the forefront, and in recent years there has been an acceleration: many new drugs have arrived for all types of breast cancer, even the “triple negative” one, considered the more difficult to treat, and especially for the advanced stage. What can we expect in 2022? “First of all, I expect an increasing use of conjugated antibodies, that is, targeted drugs that bind molecules of powerful chemotherapy drugs, capable of selectively targeting cancer cells”, he replies Saverio Cinieri, president of the Italian Association of Medical Oncology (Aiom) and director of the Medical Oncology and Breast Unit of the ‘Perrino’ Hospital in Brindisi. In fact, sacituzumab govitecan (the first of a new class of these drugs) was recently approved for triple negative cancer advanced from the second line of treatment, while at the end of 2020 trastuzumab deruxtecan had been given the green light for Her2 positive carcinoma, always advanced and always from the second line.
“These conjugated drugs have proved effective for two different patient populations – continues Cinieri – and this year we will have data on the use of conjugated antibodies in the first line of treatment”. There is no shortage of news also for the most common breast cancer, the ‘hormonal’ one: “We are awaiting the results of clinical studies on new Serd (Selective estrogen receptor degrader, ie drugs that damage the estrogen receptors present on cancer cells, ed.): there are at least 8 very promising ones currently being tested, and they will complement endocrine therapy for these patients “.
A novelty is also expected for mammography screening: “The need to extend the age of screening is increasingly clear to us: every day we find ourselves treating younger patients than in the past, and this should be our goal”.
For prostate cancer
The main innovations of 2022 lie ahead for advanced-stage prostate cancer. “What we have been carrying from previous years is the so-called sequencing, that is the staggering of therapeutic strategies with a view to chronicizing the disease”, he explains Sergio Bracarda, director of the Complex Structure of Medical Oncology of the Santa Maria di Terni Hospital. “With current therapies, namely hormonal agents and chemotherapy, we have already achieved significant increases in survival, which has gone from months to years.” In 2022, other therapeutic possibilities will be added: in addition to the advent of new generation hormonal agents and strategic combinations with chemotherapeutics, teragnostics is expected that combines an innovative diagnostic approach (PET PSMA) with the possibility of bringing a treatment to the disease sites radio-metabolic. “This approach, in addition to having shown advantages in terms of survival, is well tolerated by patients and could be applied at various stages of the disease,” adds the oncologist.
The use of PARP inhibitors will also take off: already in use in the treatment of ovarian and breast cancer, this class of drugs has been shown to be effective in terms of increasing survival in 7-15% of stage prostate cancers. advanced, i.e. those characterized by mutations of the BRCA2 and (marginally) BRCA1 gene. “Clearly departing from current standard therapies, these innovative treatments increase the chances of disease response and control where resistance has emerged.” We are at the dawn of an unprecedented scenario, that of targeted choices also for prostate cancer: “Very positive prospects, but also complex from a decisional point of view, and in which clinical experience will have an important value in choosing the therapeutic path”.
For lung cancer
Building on the results achieved in recent years, from 2022 we expect further progress in the availability of molecularly targeted drugs for patients with advanced lung cancer. “For several years we have known that individual cases are very different from each other due to the presence of different molecular alterations – he says Massimo Di Maio, national secretary Aiom and director of the Oncology of the Mauriziano hospital in Turin – and the number of alterations for which there are active drugs, able to control the disease, is constantly growing. From the near future we expect active drugs for alterations previously considered ‘orphan’ (as there were no dedicated drugs, ed.) And the possibility of therapy even for patients whose disease becomes resistant to the treatments already available ”.
Another chapter is the increase in therapeutic possibilities also for patients who, receiving a diagnosis at an early stage, can undergo surgery with the intent of healing: “Until recently, the only effective therapy in increasing the chances of chemotherapy has been healing, while recently both immunotherapy and a targeted drug have been shown to prolong relapse-free survival. In addition to further potential innovations, from the near future we expect the scientific community to update the guidelines for the use of these new therapeutic possibilities ”, explains the expert. Finally, let us not forget that the wait is often not only linked to the production of new scientific results, but also to the effective availability for patients of treatments that have already produced results but are not yet available in clinical practice: “This gap is particularly felt in lung cancer, precisely because of the high number of scientific innovations we have seen in recent years “.
For colorectal cancer
The most important news for colorectal cancer in 2022 will be the approval by the Italian Medicines Agency (Aifa) of two specific treatments for patients with metastatic disease. The first is first-line immunotherapy treatment – with pembrolizumab – in patients with microsatellite instability, which account for approximately 5% of all metastatic cancers. “This treatment, based on the results of the Checkmate-177 study, completely changed the natural history of these patients, resulting in excellent long-lasting responses and even complete responses”, he explains. Lisa Salvatore, coordinator of the Aiom Guidelines for colorectal cancer, medical director at the Gemelli Polyclinic in Rome: “Already the Aiom guidelines introduced in 2021 the recommendation to use immunotherapy as a first-line choice in these patients, since the drug is accessible through a nominal use program. Now we are waiting for the regulatory authorities to grant reimbursement “. A phase III study is also underway which is evaluating immunotherapy in all lines of treatment, not just at the front line. Based on the results, we will see if immunotherapy can also be used in the advanced lines (to date Aifa has not approved this treatment in the advanced lines because the results came only from phase II studies, smaller and more limited studies).
“The second novelty – continues Salvatore – concerns the target therapy with cetuximab (an anti-EGFR drug) and encorafenib (anti-BRAF) in metastatic patients with BRAFV600E mutation (which represent about 10% of cases, ed.) Starting from second line of treatment. “Again we had the option of using this treatment through a nominal use program. And once again the national guidelines had already inserted the recommendation in 2021. A phase III study is also underway which is evaluating the use of this combination, also in combination with chemotherapy, at the forefront. Based on the results, we will know if we can anticipate the target treatment of mutated BRAF patients at the first line ”. AIFA’s approval for these two types of treatments will make it easier and faster to access drugs.
In melanoma, immunotherapy continues to give important results, and it will also do so in 2022. “Last year we had confirmation that immunotherapy is also effective as an adjuvant therapy in the earliest stages (2b and 2C): in the study study Keynote-716, presented at the Presidential Symposium Congress Esmo 2021, the drug pembrolizumab was in fact compared with placebo and demonstrated a reduction in the risk of relapse or death by 35% “, explains Paolo Ascierto, Director of the Melanoma Oncology, Oncological Immunotherapy and Innovative Therapies Unit of the ‘Pascale’ of Naples: “We are now waiting for approval in Europe and in Italy”. Another ongoing study will also tell us indications for immunotherapy as a neoadjuvant treatment.
As for advanced melanoma, an important novelty concerns the new combination of relatlimab, an anti-LAG 3 antibody, and nivolumab, which resulted in a 25% reduction in the risk of disease progression, with fewer side effects than the nivolumab combination. and ipilimumab. “At this moment this strategy is not yet approved even in the US, but we hope that it will soon arrive”.
Last, but certainly not least, the target therapy both for patients with early stage cancer – where it has proved to be as effective as immunotherapy – and for metastatic patients. “In this case, two studies today indicate the best sequence”, Ascierto concludes: “It is better to start with immunotherapy on the front line, and continue with targeted therapies”.
Collaborated with: Anna Lisa Bonfranceschi, Irma d’Aria, Mara Magistroni.