One therapy for multiple tumors

One therapy for multiple tumors


The drug-conjugated antibody trastuzumab deruxtecan, now used in a particular type of metastatic breast cancer, also appears to be effective against other solid tumors that share one characteristic: the amplification of the HER2 gene, regardless of the affected organ. We are talking about tumors that are difficult to treat - such as advanced ones of the endometrium, cervix, ovary, urothelium and bile ducts. And also in patients who have already received multiple lines of treatment. The data comes from the congress of the American Society of Clinical Oncology, underway in Chicago, where the phase II study DESTINY-PanTumor02 has just been presented, the first among the anti HER2 to test this drug in an agnostic way, i.e. regardless of the type of tumor.

Tumors, one patient out of two has a mutation for which drugs exist

by Letizia Gabaglio


A “molecularly targeted chemo”

The term "amplification" means that a gene is present in more copies than normal and, consequently, the cells synthesize a much higher quantity of the corresponding protein (which is, therefore, over-expressed). This, in the case of HER2, translates into a boost to tumor proliferation. This genetic abnormality was discovered many years ago in breast cancer. The first drug directed against HER2, trastuzumab, was developed in the early 2000s and substantially changed the prognosis of these breast cancers. More recently other more potent drugs have been developed against the same target and trastuzumab deruxtecan is one of them. It is a drug-conjugated antibody: it is born, that is, from the union of a monoclonal antibody - trastuzumab - with the particularly powerful chemotherapy drug deruxtecan. Each trastuzumab molecule binds to 8 deruxtecan molecules. The mechanism by which it works is this: trastuzumab recognizes and binds to the protein synthesized by HER2 present on the surface of the tumor cell and releases the 8 "projectiles" (i.e. molecules) of the chemotherapy inside it.

There is a therapy for every cancer. Cancer is increasingly treatable

by Daniela Minerva



HER2 in colorectal cancer

The discovery that HER2 could also be an important target in other solid tumors in addition to breast cancer is Italian, and dates back to more than 10 years ago. “In 2011, researchers from Turin published in Nature the evidence that HER2 was also implicated as an oncogene in colorectal cancer - he explains Salvatore Siena, Director of the Falck Oncology Complex Structure of the Niguarda Cancer Center and Full Professor at the State University of Milan, one of the authors of the paper presented today in Asco - From there we focused on metastatic colorectal cancer and in 2015 we published the study clinician who was the first to demonstrate that anti-HER2 therapy is also effective in this tumour. This therapy with trastuzumab deruxtecan is particularly powerful, as we had shown in 2021 in another study also in Lancet Oncology precisely on HER2 positive colorectal cancers, even if already treated with other anti-HER2 drugs ". Other trials had then investigated the strategy also for gastric tumors.

Tumors, multidisciplinary teams and genomic profiling tests are needed for precision medicine

by Irma D'Aria



The new studio

The new DESTINY-PanTumor02 study goes one step further and tests the new drug in many other types of neoplasms, even rare ones, including those of the salivary glands, oropharynx, vulva, with unknown primary site, in Extramammary Paget, in melanoma. Overall, 267 patients with advanced or metastatic tumors progressing after at least one line of treatment or for whom there are no approved therapeutic options were enrolled. All received trastuzumab deruxtecan. 9.7 months after administration (median time), 37% of patients responded to therapy and this was maintained over time, with a median of 11.8 months without disease progression. The best results were observed in patients with a high overexpression of the HER2 protein: here the response was over 61% and its duration was 22 months.

Female tumours: in 10 years +34% of women are alive after diagnosis

by Irma D'Aria



The best results for gynecological cancers

Looking specifically at the data for the tumors that responded best, we find that of the endometrium (response of 57.5% on average and 84.6% for over-expression of HER2); of the cervix (50% and 75%, respectively); of the ovary (45% and 63.6%, respectively); of the urothelium (39% and 56.3%, respectively); bile ducts (22% and 56.3%, respectively). “It should be emphasized that these are patients who in 40% of cases have had more than 3 lines of treatment and in 30% more than two, so these results are really important - comments Siena - Furthermore, more than 10% had already done an anti-HER2 therapy. The other interesting aspect is that these responses are maintained over time: there are patients who have maintained the regression or blockage of the disease for up to two years".

Bladder cancer: 61% of patients never reported symptoms to the doctor



Waiting for confirmations

This study provides data on patients who have exhausted standard treatment options with HER2-overexpressing tumors, for which no drugs are yet approved, comments Bradley Alexander McGregor, Asco expert: “Although further follow-up is needed, they show strong activity across multiple tumors, with a response rate of more than 50% in those with the highest levels of HER2 expression, along with an encouraging safety profile . Trastuzumab deruxtecan could represent a new therapeutic option for these patients”. The study (which, we recall, is in phase II) is in fact still ongoing. "If the results are confirmed by a longer follow-up - concludes Siena - in my opinion they contribute to an approval for competitive use of the new drug in solid tumors with HER2 amplification".



Source link