Adnkronos (Adnkronos) – L’immunoterapia “può evitare molte delle sequele legate agli effetti collaterali del percorso tradizionale di cura e rappresentare lo standard of care per i pazienti con tumore del retto localmente avanzato che non hanno metastasi, ma che hanno una malattia abbastanza estesa, nel retto, a livello locale, e deficit del sistema mismatch repair (dMmr/Msi-H)”.
Così Chiara Cremolini, professore ordinario di Oncologia all’università di Pisa e membro del direttivo nazionale dell’Associazione italiana di oncologia medica (Aiom), commenta i risultati dello studio Azur-1 che ha interessato l’impiego di dostarlimab, presentato al congresso della European Society for Medical Oncology (Esmo) in corso a Madrid.
Il trial “che ha arruolato 154 pazienti in tutto il mondo – illustra Cremolini – ha dimostrato che circa il 70% ottiene una risposta clinica completa dopo 6 mesi di trattamento con dostarlimab, senza avere bisogno di ulteriori trattamenti, né radioterapia né chirurgia, con le relative potenziali sequele.
Questa risposta clinica completa si mantiene per almeno 12 mesi, cioè un anno. Si tratta dunque di una percentuale molto elevata di pazienti che raggiungono questo risultato”. Inoltre, nei pazienti “che non ottengono una risposta clinica completa e che vengono quindi operati – precisa – si osserva una risposta patologica completa in un’altissima percentuale: 10 casi su 13.
Questo significa che, nel pezzo operatorio, il tumore non è più presente. Il farmaco – aggiunge – ha ricevuto da poco l’approvazione dall’Fda negli Stati Uniti. L’Ema”, l’Agenzia europea dei medicinali, “non l’ha ancora approvato per questa indicazione. In Italia però lo utilizziamo da tempo grazie all’inserimento del dostarlimab nell’elenco dei farmaci previsto dalla legge 648, quindi attualmente non è rimborsato dal Servizio sanitario nazionale, ma può essere utilizzato per questi pazienti non a loro spese”.
Historically, standard treatment for patients "involved chemoradiotherapy followed, a few weeks later, by surgery," the oncologist explains. "Clearly, this entire process has significant consequences in terms of fertility, especially in women, but also in terms of sexual function and, not least, the need for temporary or, unfortunately, permanent stomas. Therefore, although it has demonstrated a clear benefit in curing these patients, it still leaves significant consequences. A particular subtype of rectal cancer patients, which accounts for less than 5% of cases, is characterized by a deficiency in the DNA mismatch repair system. These are tumors in which errors accumulate, making them visible to the immune system but slowing down its response. If we unblock the immune system, which immunotherapy does, we can therefore achieve a very effective antitumor effect."
This was demonstrated with dostarlimab "in a previous study, conducted on about fifty patients exclusively in the United States, at Memorial Sloan Kettering in New York," Cremolini emphasizes. "The study demonstrated that this therapy, alone, allowed patients to achieve a complete clinical response, without the need for subsequent radiation therapy or surgery. This is an extraordinary result for their quality of life. This has now been confirmed by the Azur-1 study, a much larger, global study. When you move from a single hospital to many centers, you have proof that the outcome doesn't depend solely on the excellence of a given facility, but is actually linked to the treatment. Further data will be presented with a more mature follow-up. For now, the goal was to verify how many patients managed to maintain a complete clinical response for at least 12 months, which represents a significant interval from the start of therapy."
Testing is essential to identify this type of tumor. "Today, all pathologists who diagnose rectal adenocarcinoma are well aware of the therapeutic relevance of this information and routinely include it in the report," assures the oncologist. "The test is performed everywhere because it involves a technique called immunohistochemistry, which is available in all centers and is also inexpensive. Furthermore, this same test is useful for diagnosing colon cancers associated with a hereditary predisposition, particularly those related to Lynch syndrome. It is therefore a test that can have, on the one hand, very significant therapeutic implications and, on the other, allow us to identify hereditary syndromes. This aspect is important because a person could develop other tumors, with a different risk than those without this predisposition. Furthermore, it is possible to test family members, if they wish, and initiate a screening program different from that provided for the general population."
In managing this type of tumor, "it is absolutely clear," Cremolini emphasizes, "that a multidisciplinary team is necessary. This team includes, in addition to the medical oncologist, a dedicated radiologist (because radiological staging is crucial), a surgeon, a radiation oncologist, and, increasingly, specialists capable of interpreting information from molecular biology, in this case, pathological anatomy. In the case of rectal cancer with mismatch repair deficiency, this multidisciplinary approach is even more important to define the clinical response and determine whether the patient should take additional action or whether the result achieved with dostarlimab is sufficient. It is also a process of growth within the multidisciplinary team. The more we see these cases," he concludes, "the more we understand how best to manage them, all together."
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