For the first time, long-term data are available on the combination of two different therapies that work against cancer by stimulating the immune system. And they are very comforting data. 48% of kidney cancer patients treated on the first line with the combination of immuno-oncology molecules, nivolumab and ipilimumab, are alive at 5 years. Also thanks to this approach, in mesothelioma 23% of patients never treated before are alive at 3 years. In both cases, unique results, unthinkable a few years ago. The data comes from two studies presented at the Congress of the European Society of Medical Oncology (ESMO), running until 21 September. The advances in the adjuvant treatment of esophageal cancer with nivolumab, i.e. following pre-operative chemo-radiotherapy treatment and surgery, were also presented during the virtual congress, with the aim of reducing the risk of relapse.
The combo in the kidney
In 2020, 13,500 new cases of kidney cancer were estimated in Italy and more than 144,000 people live after diagnosis. The most frequent form is that of kidney cells. “Over 50% of patients with early stage disease recover – says Carmine Pinto, Director of Medical Oncology Comprehensive Cancer Center AUSL-IRCCS of Reggio Emilia -. However, 30% reach the diagnosis already in an advanced stage and, in a third, the disease can recur in metastatic form after surgery. Historically, 5-year survival in advanced or metastatic disease did not exceed 13%. Today, however, thanks to the combination of the two immuno-oncological molecules, almost half are alive at 5 years old ”. The presented study involved 1,096 people with advanced renal cell kidney cancer and evaluated nivolumab plus ipilimumab against the sunitinib standard of care at the forefront. The follow up was 67.7 months. In this phase 3 study, median overall survival reached 55.7 months with the combination. In all randomized patients, the five-year overall survival rates were 48% with nivolumab plus ipilimumab compared to 37% with sunitinib. The combination also showed a higher overall response rate than sunitinib (39% versus 32%). “The combination of immunotherapy significantly improves and lengthens long-term life expectancy, as evidenced by the sub-analyzes – continues Pinto -. Patients alive at 3 years after starting treatment with nivolumab plus ipilimumab had an 81% chance of still living in the next two years, and progression-free patients at 3 years had an 89% chance of remaining in this condition. for another 24 months. It is therefore an important weapon that we hope to be able to use on patients soon ”.
The combination showed improvements in overall survival in six phase 3 studies involving 5 different cancers: in addition to renal cell carcinoma, non-small cell lung cancer, melanoma, squamous cell esophageal cancer and mesothelioma. pleural. “Unfortunately for the latter tumor, the therapeutic options are limited – explains Pinto -. Chemotherapy has shown benefits in the late stage, with only 10% of patients alive at 5 years. The data presented at ESMO represent a step forward in the therapeutic strategy “. The presented study involved 605 patients and demonstrated that, at a minimum follow-up of 35.5 months, the combination of nivolumab and ipilimumab in the first line reduces the risk of death by 27%, showing a median overall survival of 18.1 months compared to 14.1 months with chemotherapy. In the study, the immunotherapy combination demonstrated a clinically significant improvement in survival, with 23% of patients still alive at three years compared with 15% with chemotherapy. The benefits of the combination also last over time with a median duration of response of 11.6 months compared to 6.7 months for chemotherapy. “Before we only had the first line of therapies, now we know we can start with immunotherapy and postpone chemo; therefore have a composite strategy, which also involves genetic analysis because there are markers of greater and lesser sensitivity to therapies ”, says Pinto.
In esophageal cancer
Another neoplasm with limitations and difficulties in the cure is the tumor of the esophagus. And again, immunotherapy opens up new treatment options. The data presented highlight the efficacy of nivolumab administered as adjuvant therapy, i.e. after surgery, in patients who had residual disease in the surgical piece after pre-operative chemo-radiotherapy, with a 33% reduction in the risk of relapse and a excellent tolerability of the treatment. An important result since it is one of the worst prognosis neoplasms, with a 5-year survival of 13%, and for which there is an increase in cases: in five years (2015-2020), in Italy, new cases of esophageal cancer increased by 26%, from 1,900 to 2,400.