The month dedicated (also) to pancreatic cancer ends today. And precisely in order not to draw attention to this neoplasm that is still difficult to treat, let’s tell a story of hope. It is not so much – or not only – the story of a single person, but how a treatment strategy shared by several centers – which really work in a network – can make the difference for the survival and quality of life of patients. As a reminder that while each case is unique, a good model can improve the care of many.
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by Irma D’Aria
From diagnosis to the possibility of a clinical study
So let’s start from the story of Elena (invented name): the diagnosis of pancreatic cancer in an advanced stage, with liver metastases, had arrived in September 2017, when she was about 60 years old. A common age for this disease. “The patient had been sent to us from another center with which we work on the network,” she says Michele Reni, director of the strategic clinical coordination program of the Pancreas Center of San Raffaele in Milan: “The colleagues who treated her knew that we were conducting two clinical studies in which, perhaps, she could have entered. In fact, each trial has very stringent access criteria, which must be respected in order to correctly evaluate the efficacy and safety of the new drugs”. One of the studies was not suitable for Elena’s disease. For the other instead – the POLO study which concerned the use of a targeted drug olaparib (of the class of Parp-inhibitors) in tumors with mutations in the BRCA genes – it was necessary to wait for the outcome of the genomic test.
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In the meantime, Elena had returned to treatment at her centre. Here, close to his home, for six cycles he had therefore received a combination of 4 chemotherapies (which in a previous Italian multicenter phase 3 study had obtained, for the first time in the history of pancreatic cancer, results significantly superior to the use of a single chemotherapy). In the meantime, the result of the test had also arrived: her tumor presented a BRCA mutation and, once the therapy was over, she would have been able to enter the POLO studio at the San Raffaele. “In the 12 months that followed the start of the trial, the liver metastases had completely disappeared and the patient was operated on to remove the tumor still located in the tail of the pancreas”, continues Reni: “By analyzing the data afterwards, we then discovered that, in fact, she had ended up in the placebo arm and therefore had not received the new drug. The disappearance of the metastases was therefore due to the prolonged effect of the previously received 4-drug chemotherapy”.
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Relapse and the new experimental drug
Only two months after the surgery, however, the tumor had returned. Another six months of 4-drug chemotherapy awaited her, therefore, which also proved to be very effective in his case. “It was February 2020 – continues the expert – and the POLO study on olaparib was now closed. However, pending the decision on its reimbursement by the Italian drug agency, the manufacturer had launched an early access program: all patients with pancreatic cancer and with BRCA mutations, including those who had participated in the POLO study in the placebo arm, they could have received it.” Since then, Elena has been on olaparib and her CT scans continue to be negative. “We certainly cannot call it cured – clarifies Reni – What we can say, however, is that with this drug we are observing several cases of long survival, even five years after diagnosis: a figure never observed before in advanced pancreatic cancer”.
Not individual reference centres, but a network
The ‘lesson’ to be learned in the month dedicated to this neoplasm, according to experts, is therefore the importance of collaborating between doctors. “We think it is wrong, for this disease, to have a few reference centers in which to centralize all cases”, underlines the expert: “Rather, it is important to consolidate a network of hub centers and spoke centers that share therapeutic strategies, treatments and information on experimental studies, which may not necessarily be the solution, but they certainly represent an opportunity. And, last but not least, that they give patients the opportunity to be treated close to their home”.
The non-refundability of olaparib
One aspect of this affair touches on a delicate issue: that of the AIFA decision – arrived exactly one year ago – not to reimburse olaparib for these patients, because the POLO study has not clearly demonstrated that it is able to prolong the patients’ lives treated with the drug compared to a placebo, but ‘only’ to allow them to avoid the worsening of the disease for a longer period and, consequently, the need to use more toxic chemotherapy. “The early access program is now closed, so anyone who falls ill today with pancreatic cancer and has the BRCA mutation will not be able to receive the drug”, recalls Reni: “The Parp-inhibitor is recommended in international guidelines, two scientific associations, 230 oncologists and patient associations have sent letters to AIFA to ask for a re-evaluation, but to date there has been no response”.
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At the last congress of the European Society of Medical Oncology (Esmo), the new data from the early access program in daily clinical practice were presented by Michele Milella, head of the University of Verona oncology and head of pancreatic pathology. In this experience, the Parp-inhibitor olaparib, administered as maintenance therapy after platinum-based chemotherapy, doubled long-term survival: 34% of patients survived beyond three years, compared with 18% of those who did not receive the drug. “Unfortunately, it is likely that for Aifa these results cannot represent superior evidence to that already provided by the previous clinical study, which was the result of an immense effort”, concludes Reni: “But at the same time we clinicians hope that the agency can take this into account, because they confirm that people with this disease live longer than we could ever have expected so far, and start a debate as soon as possible ”.