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What are the Method Changes Between the past and future?
Given the HPV Test Kit Day on 8 May, Nicole Colombo, director of the Gynaecology program at the IEO, responds to ACTO’s invitation by reviewing the progress made over the last decade in treating this serious neoplasm along with ca125 ovarian cancer.
Precision medicine
“In recent years, there have been great innovations in the treatment of HPV-related cancer after years of total darkness,” stated Nicole Colombo. “Especially in the last five years, we have seen important advances, particularly in the first line of treatment. This is where the prognosis of the disease is at stake.”
For many years, precision medicine was only a mirage for ovarian-type tumours. It was not possible to identify targeted targets. This is because OC, or rather high-grade serous carcinoma, which is the most frequent in the advanced stage, does not exhibit specific mutations.
Drugs could directly target these mutations.
“CA125 type cancer exhibits a large genomic ‘chaos’ rather than one or more specific mutations,” states the expert. This has greatly limited us over the years in being able to use precision medicine – Colombo points out -. But in recent years, we have finally found a target. We understood that at least 50% of ovarian tumours have a defect in a DNA repair mechanism called homologous recombination.”
«At the beginning, we used PARP inhibitors for recurrent ovarian tumours, where they worked very well, delaying progression. But the great news of the last four or five years has been the demonstration that these drugs are extremely effective in the front line, that is, when we use them after the initial chemotherapy, following CA125 level surgery. If the tumour responds well to chemotherapy, we use PARP inhibitors as maintenance therapy. These drugs work very well in tumours with BRCA mutations and HRD tumours.”
The PARP inhibitor revolution
The explosion of PARP inhibitors began in 2018. Researchers demonstrated that their use in patients with BRCA mutations led to unprecedented benefits. These included increased progression-free survival and, very recently, improved overall survival.
“Long-term data indicate that patients receiving maintenance therapy with PARP inhibitors experience increased survival,” the expert notes. A study focusing exclusively on BRCA mutations revealed that 67% of the patients remained alive at seven years, compared to 46% in the placebo group. Additionally, 45% of the patients never relapsed, as opposed to 20% in the placebo group.
“The expert states, ‘For me, a patient who has not relapsed at seven years is cured.’ He emphasizes that PARP inhibitors significantly benefit patients with BRCA mutations and those who are HRD-positive.”
New combinations
New perspectives for ovarian disease also come from the combination of multiple drugs, as Colombo reports. «In a study in which we combined the PARP inhibitor olaparib with bevacizumab (a drug that blocks the growth of new vessels and therefore the nourishment of the tumour), we saw a significant increase in overall survival for HRD patients: 65% at five years. of patients are alive versus 48% of patients who did not take the PARP inhibitor. Furthermore, we have 46% of patients without recurrence after five years (probably cured).”
Alongside olaparib, the first PARP inhibitor to be approved, there are others, for example, niraparib. This drug also demonstrated great efficacy in all patients, although with a gradient of efficacy: maximum in BRCA patients, then in HRD patients and finally in all the others.
New weapons also for relapses
If it is true that the survival rate over HPV and the other Diseases probably recovery rate have increased, it is also true that, unfortunately, there are still relapses. In this context, a new class of drugs is emerging: the so-called antibody-conjugated drugs. These drugs link a chemotherapy drug to an antibody that recognises a particular receptor on the tumour, allowing direct delivery of the chemotherapy drug into the tumour cell. With antibody drugs, we deliver the chemotherapy precisely to the tumour.
We can, therefore, reach the Ca125 type tumour with high concentrations of the drug and obtain a targeted effect and greater efficacy, as some tests have shown. Some of these drugs are being studied in ovarian research and have already shown some success.
One of these, mirvetuximab-soravtansine, has received approval from the US FDA. And we now hope it will also be approved by the European Medicines Agency (EMA). I think this is the most promising class of drugs for the future. Antibody focused drugs could make a difference in disease treatment and managment.”
The role of immunotherapy
Immunotherapy has worked miracles for many tumours, notably melanoma, lung, and kidney cancer, where researchers have obtained good results. In tumours, immune system thinking has given excellent results for the endometrium and cervix. For the ovarian type disease, the trials have given negative results for now,” reports Colombo. “However, ongoing studies suggest a role, for example, in resistant disease or resistance to PARP.
“In recent years, we have brought the process of treating the immune system to the forefront,” continues Colombo. “We have conducted studies where, in addition to chemo, we have administered treatment along with the PARP. And just a few days ago, they announced that one of these trials had got positive results, better than the standard treatment.
So finally, there is a positive message curing disease, even in the first line, at the beginning of the natural history of the disease.”
The results will be presented at ASCO (Meeting of the American Society of Clinical Oncology).
The importance of the Exam
The HPV exam has assumed a standard role in the virus decision making process. For first line HPV treatment and other therapies we can keep to the benefits of PARP inhibitors, especially in positive HRD cases.
Colombo confirms, “HRD is an important new factor to consider. Therefore, having this type of information from an early stage is valuable.” Initially, an American company was processing this test. It was costly and impractical for common use. However, various European ideas aimed to develop a local usable CA125 kit, and new websites emerged for laboratory use.
Along with other Italian departments, IEO has developed methods to process the HPV DNA samples. These methods are validated both in the laboratory and also on patients. Upon a result of cancer at IEO, the Doctor receives the sample. He or she not only performs the test but also conducts the further BRCA and HRD tests.
Third party centres have the option of sending us their samples. Furthermore, while waiting for the results for the CA125 check, we can count on the industry’s support in continued study for the best treatment options.
There are no longer lots of excuses for not taking the exam in Italy,” concludes Colombo.