Trials show progress for the 18,000 Italian patients who have already received multiple therapies and are no longer benefiting from standard care
When colon cancer is discovered at an early stage, over 90% of patients are cured. In two out of ten cases, however, the neoplasm was already diagnosed in metastatic stage and then there is a quota of patients in whom, over time, the disease evolves into advanced forms. So, according to statistics, about 18,000 Italians live today with metastatic colorectal cancer. in these cases the use of may be useful new drugs able to lengthen the survival of patients who have already received several lines of treatment and who have become resistant to standard care. The experts meeting in Naples for The Naples Conference on colorectal cancer are discussing the new possible strategies and the most promising drugs being tested these days.
Cases on the rise, even before the age of 50
With over 48 thousand new cases registered every yearcolorectal cancer is the second most frequent type of cancer in our country and also the second in the little sought-after ranking of the deadliest, causing about 19 thousand deaths per year. Nine out of ten cases could be avoided because there is an effective, free (in Italy) and completely painless method to eliminate pre-cancerous lesions before they turn into a real neoplasm: the occult blood test in the feces. Seven out of ten Italians, however, do not accept the invitation to carry out checks and statistics indicate that colorectal cancer is increasingly widespread, even before the age of 50. Thanks to the new therapies, survival has improved and an average of 65% of patients are alive five years after diagnosis – he says Fortunato Ciardiello, full professor of the Department of Precision Medicine of the University of Campania Luigi Vanvitelli and scientific coordinator of the conference -. Numerous researches conducted in recent years have brought to light that essential, for a correct treatment of metastatic colorectal cancer, genetically test all patients to choose the best treatment (among the many available), based on the biological characteristics of the tumor and any genetic alterations present.
Genetic tests to choose the cure
Precision oncology requires that the molecular characteristics of the neoplasm be identified, i.e. the genes that help establish the most appropriate treatment on a case-by-case basis. There are some genetic alterations which, if present, can provide the clinician with very important information on thebiological aggressiveness of the tumor and on the possibility of responding or not to treatment. Two studies recently presented at the ASCO Gastrointestinal Cancer Symposium in San Francisco go in this direction on two specific monoclonal antibodies and targeted against important targets for tumor growth (bevacizumab and panitimumab), which they can double patient survival with metastatic colorectal cancer refractory to standard therapies.
New combination for those who do not respond to therapies
Standard trifluridine/tipiracil treatment of therapy-refractory metastatic colorectal cancer was added in the phase III multicenter international study SUNLIGHT bevacizumab, an antibody directed against vascular growth factor VEGF which can block the growth of new blood vessels. The patients, around 500, were complex cases, already treated with one or two lines of therapy – explains Ciardiello, co-author of the trial -. With combined therapy the median survival rose to 10.8 months compared with 7.5 with standard treatment. Clinical benefit emerged in all patient subgroups regardless of age, gender, location of the primary tumor, number of metastases, or the presence or absence of RAS mutations, which may affect therapy; combined treatment also doubled progression-free survival, which went from 2.4 to 5.6 months. The clinical benefit was also seen in patients who had already been treated with bevacizumab, indicating that continuing to inhibit the formation of new blood vessels that feed the tumor may have important clinical significance even during disease progression. Disease control rate increased by 30% to 77%: a remarkable result and in the absence of an increase in toxicity. All of this points to the combination of bevacizumab with trifluridine/tipiracil as a possible new standard of care for these patients, for whom we previously had few treatment options.
Third line of therapy
Also the second study, at the center of discussions during the Neapolitan congress, envisaged the addition of an antibody to the standard therapy of refractory metastatic colorectal cancer. The VELO phase II clinical trial involved 62 patients from six Italian centers and was coordinated by the University of Campania Luigi Vanvitelli: in this case the panitumumab, a monoclonal antibody directed against the epidermal growth factor receptor EGFR, in combination with trifluridine/tipiracil in a defined rechallenge strategy. It’s about the resumption of treatment with anti-EGFR drugs in the third line of therapyin patients who, after an initial response, unfortunately had disease progression and therefore received a subsequent, different treatment – he explains Teresa Troianiof the Department of Precision Medicine of the University of Campania Luigi Vanvitelli, among the authors of the VELO study together with Ciardiello —. In these patients the metastatic disease recovers and becomes resistant to therapies: Poor prognosis and current third-line treatments are effective in a relatively small proportion of patients. Adding panitumumab to standard therapy increased PFS from 2.5 to 4 months and increased disease control from 48 to 81% compared to standard treatment alone. A figure that is only apparently small, but of great significance.
Save time in small steps
Researchers are proceeding in small steps, but with noteworthy progress because even if healing is not achieved, months of freedom can be gained between one treatment cycle and the next with the aim of making the disease chronic, lengthening the survival of the patients and giving them time with a good quality of life and the least possible amount of side effects. To monitor the evolution of the tumor in real time with the experimental therapies administered, the trial participants also received a liquid biopsy, an avant-garde test used to evaluate in advance the response to treatment or identify resistance mutations. A liquid biopsy was also performed in the patients to analyze whether they had RAS and BRAF mutations that could affect the effectiveness of the treatment. Erika Martinelli, of the Department of Precision Medicine of the University of Campania Luigi Vanvitelli and one of the authors of the study —. The test, which consists of the plasma collection with a simple blood sample to highlight the presence of mutations that characterize the neoplasm in the circulating DNAderived from individual patient tumor sites, was also repeated at disease progression to evaluate the possible appearance of mutations.
March 16, 2023 (change March 16, 2023 | 08:06)
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