The range of possible therapeutic opportunities is widening thanks to immunotherapy for gastrointestinal tumors, which is constantly increasing year after year also due to bad lifestyle habits, starting with an incorrect diet. The good news comes thanks to two provisions of the Italian Medicines Agency (Aifa) which recently approved the reimbursement of nivolumab, an immunotherapy drug, in combination with chemotherapy as a first-line treatment in adenocarcinoma of the stomach, gastro- esophagus and esophagus in HER2 negative and PD-L1 patients with combined positive score (CPS) ā„ 5. Aifa also gave the go-ahead for reimbursement of dual immunotherapy, nivolumab plus ipilimumab, in highly unstable metastatic colorectal cancer of microsatellites or mismatch repair deficiency, after previous fluoropyrimidine-based chemotherapy. Two important innovations that were presented today in Rome at a press conference promoted by Bristol Myers Squibb.
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gastrointestinal tumors
Gastrointestinal tumors are frequent neoplasms in Western countries, in particular colorectal cancer, which registers almost 44,000 new cases every year in Italy. “The incidence of stomach and oesophageal cancer is lower, for which an estimated 14,500 and 2,400 new diagnoses each year in our country, respectively – he says Ferdinand DeVita, director of the Precision Medicine Department and Professor of Medical Oncology at the Luigi Vanvitelli University of Naples in Campania. āThe 5-year survival is also different, equal to 65% in the colorectal, 32% in the stomach and only 22% in women and 13% in men in the esophagus. These differences are also attributable to the availability in Italy of effective screening programs for colorectal cancer, which allow for the identification and removal of adenomatous polyps, which constitute the most common preneoplastic lesion before their transformation”.
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How important are lifestyles?
Incorrect lifestyles are the main risk factors. “The excessive consumption of red meat, sausages, refined flours and sugars, obesity, sedentary lifestyle, smoking habits and alcohol abuse play a central role in the development of colorectal and stomach cancers,” he continues. DeVita. Obesity and gastroesophageal reflux disease are the predominant risk factors for adenocarcinoma of the esophagus, which has become the most frequent neoplastic form affecting the esophagus in Western countries. Instead the abuse of alcohol and the habit of smoking cigarettes and consuming very hot drinks and foods are closely connected to the scaly formā.
Even 2022
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Little chance of cure
Gastric adenocarcinoma accounts for 95% of stomach cancer cases. āUnfortunately, only 7% are identified at an early stage ā he explains Stefano Cascinu, Director of the Oncology Department IRCCS San Raffaele Hospital in Milan and Professor of Medical Oncology at the Vita-Salute San Raffaele University. āAdvanced or metastatic gastroesophageal (stomach, gastro-esophageal junction, and esophagus) adenocarcinomas receive the same systemic treatment with chemotherapy and for over 20 years there has been no progress and benefits have been limited, especially in the HER2 negative forms ā.
Progress thanks to immuno-oncology
Today, however, immuno-oncology is also changing clinical practice in the treatment of gastrointestinal cancers. In the pivotal study CheckMate -649, median overall survival with immuno-chemotherapy reached 14.4 months compared with 11.1 months with chemotherapy alone in patients expressing PD-L1 with CPS ā„ 5. In addition, 13% of patients treated with the immunotherapy-based regimen achieved complete response, i.e. radiological disappearance of all signs of disease.
The advantages of the ‘double’
In short, substantial changes are underway in the treatment of gastrointestinal neoplasms. “Thanks to Aifa’s approval – continues Cascinu – we can finally offer patients an effective option, consisting of immunotherapy with nivolumab in combination with chemotherapy which, as highlighted in the CheckMate -649 study, is able to significantly improve both overall and progression-free survival. The latter was shown to be 8.1 months in the population expressing PD-L1 CPS ā„ 5 compared to 6.1 months with standard treatment. 60% of patients treated with the combination achieved an objective response compared with 45% with chemotherapy alone. In 13% of patients we observed complete responses. A very important result in which we expect to see the benefits of immunotherapy also in the long term. Added to these advantages is a good quality of lifeā.
Correctly identify patients
Patients who are candidates for therapy with the combination of nivolumab and chemotherapy, based on the approval of Aifa, are approximately 60% of the total with advanced disease. āIt is a really important percentageā, continues Cascinu. āIt is therefore crucial to identify people who can receive nivolumab-based first-line treatment, which can change the natural history of the disease.ā
The importance of proper dietary plans
The news of this novelty is one more hope that comes for patients and their families who have many requests to be able to improve the quality of life. “Caring for people with stomach cancer, especially in the advanced stage of the disease, requires a multidisciplinary approach, which can also improve the quality of life – he points out Claudia Santangelo, president of ‘Living without a stomach (you can)’. Gastrectomy, the operation to remove the stomach, changes eating habits and can cause significant weight loss. You learn to eat with new rhythms, to cope with the lack of elements such as vitamin B12, iron, folin, and glycemic swings. It is essential that dietary plans are offered to the patient by the multidisciplinary team. Furthermore, we have been waiting for new effective therapies at the forefront of metastatic disease for some time. This new treatment option represents a decisive step forward for patients.ā
Colorectal cancer
Immunotherapy also becomes a cornerstone in the treatment of colorectal cancer. AIFA has approved nivolumab plus ipilimumab for the treatment of metastatic cancer with mismatch repair deficiency (dMMR) or elevated microsatellite instability (MSI-H), after prior fluoropyrimidine-based chemotherapy. āMetastatic colorectal cancer is an aggressive disease with a poor prognosis ā he underlines Sara Longardi, acting director of Oncology 3 at the Veneto Irccs Oncological Institute in Padua. Most patients are not eligible for potentially curative surgery. The combination of nivolumab and ipilimumab is the first approved dual immunotherapy treatment option in gastrointestinal cancers, particularly in colorectal cancer already resistant to standard therapies.”
Dual immunotherapy in colorectal cancer
In the CheckMate -142 study, dual immunotherapy demonstrated a significant improvement in objective response rate. āIt reached 65%, with 13% complete responses, but more importantly, it led to a 4-year survival in 70% of patients, when the expected, in a similar context of patients with pretreated disease, did not selected molecularly who have not received immunotherapy, is 25% at one yearā, continues Lonardi.
Patients with high microsatellite instability
The study involved patients with a mismatch repair defect or with high microsatellite instability, the protein complex responsible for ‘correcting’ DNA replication errors. āAbout 5% of cases of metastatic colorectal cancer – continues Lonardi – present this characteristic, which for years seemed to reduce the probability of benefiting from traditional chemotherapy, but which now turns into an advantage in a certain sense, since it selects a subgroup of patients highly responsive to immunotherapy and in particular to nivolumab and ipilimumabā. Furthermore, the data demonstrated that the treatment was well tolerated and led to an improvement in the patients’ quality of life. āWe were pioneers in the discovery of immunooncology, a new class of drugs that leverage the potential of the immune system and which is used in the most advanced forms of metastatic disease but also in the early stages of cancer as adjuvant therapy, when the immune system may potentially be more responsive to treatment,ā he concludes Cosimo Pays, Executive Country Medical Director, Bristol Myers Squibb Italy. Over the past year, the combination of nivolumab and ipilimumab has been reimbursed in the first line in several malignancies such as melanoma, non-small cell lung cancer, renal cell carcinoma and pleural mesothelioma.