Gastrointestinal tumors, ok from Aifa to new immunotherapy indications

Immuno-oncology therapy changes clinical practice in the treatment of gastrointestinal cancers. Aifa (Italian Medicines Agency) has approved the reimbursement of nivolumab, an immunotherapy drug, in combination with chemotherapy as first-line treatment in adenocarcinoma of the stomach, gastro-esophageal junction and esophagus in Her2 negative and PD patients -L1 with combined positive score (CPS) ≥ 5. 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≥ 5. Furthermore, 13% of patients treated with the immunotherapy-based regimen achieved complete response, i.e. radiological disappearance of all signs of disease. Aifa also gave the green light to the reimbursement of dual immunotherapy, nivolumab plus ipilimumab, in metastatic colorectal cancer with high microsatellite instability or mismatch repair deficiency, after previous fluoropyrimidine-based chemotherapy. The substantial changes in the treatment of gastrointestinal neoplasms were illustrated today in Rome at a press conference promoted by Bristol Myers Squibb.

“Gastrointestinal tumors are frequent neoplasms in Western countries, in particular colorectal cancer, which records almost 44 thousand new cases every year in Italy – says Ferdinando De Vita, director of the precision medicine department and professor of medical oncology at the University of Campania Luigi Vanvitelli of Naples -. The incidence of stomach and oesophageal cancer is lower, with an estimated 14,500 and 2,400 new diagnoses each year in our country, respectively. The 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”.

Incorrect lifestyles “represent the main risk factors – continues De Vita -. Excessive consumption of red meat, sausages, refined flours and sugars, obesity, physical inactivity, smoking habits and alcohol abuse play a central role in the development of colorectal and stomach cancers. 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 form”.

According to Stefano Cascinu, director of the Oncology department of the Irccs San Raffaele Hospital in Milan and professor of Medical Oncology at the Vita-Salute San Raffaele University, “gastric adenocarcinoma represents 95% of cases of stomach cancer”. “Unfortunately, only 7% are identified in the initial phase – Cascinu continues -. Advanced or metastatic gastroesophageal (stomach, gastroesophageal junction, and esophagus) adenocarcinomas receive the same systemic treatment as chemotherapy, and for more than 20 years there has been no progress and benefits have been limited, especially in the Her2 negative forms. Today, thanks to Aifa’s approval, 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 ≥ 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 life”.

Patients who are candidates “for therapy with the combination of nivolumab and chemotherapy, based on the approval of Aifa – underlines Cascinu – are about 60% of the total with advanced disease, a truly important percentage. It is therefore crucial to identify people who can receive nivolumab-based first-line treatment, which can change the natural history of the disease.”

“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 – highlights Claudia Santangelo, president of ‘Living without stomach’ -. 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.”

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.

“Metastatic colorectal cancer is an aggressive disease with an unfavorable prognosis – underlines Sara Lonardi, director of Oncology 3 of the Veneto Oncological Institute Irccs of 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. In the CheckMate -142 study, dual immunotherapy demonstrated a significant improvement in the objective response rate reaching 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, not molecularly selected who have not received immunotherapy, is 25% at one year”.

“The study involved patients with a mismatch repair defect or with high microsatellite instability, the protein complex responsible for ‘correcting’ DNA replication errors – concludes Lonardi -. Approximately 5% of metastatic colorectal cancer cases have this feature, which for years seemed to reduce the likelihood of benefiting from traditional chemotherapy, but which now turns somewhat advantageous, as it selects a very subgroup of patients responsive to immunotherapy and in particular to nivolumab and ipilimumab. Last but not least, the treatment is well tolerated and has led to an improvement in the patients’ quality of life”.