Julien Taïeb, MD, PhD, on Treating Colorectal Cancer With Trifluridine and Tipiracil Plus Bevacizumab
2023 ASCO Gastrointestinal Cancers Symposium
Julien Taïeb, MD, PhD, of Hôpital Européen Georges Pompidou, Université Paris-Cité, discusses the clinical implications of new phase III findings from the SUNLIGHT study, which showed that trifluridine and tipiracil (FTD/TPI) plus bevacizumab resulted in improved outcomes compared with FTD/TPI alone in patients with refractory metastatic colorectal cancer. This three-drug regimen may represent a new standard of care for patients whose cancer has progressed despite two lines of therapy (Abstract 4).
Disclaimer: This video transcript has not been proofread or edited and may contain errors.
SUNLIGHT is a large phase III randomized trial conducted in patients pre-treated with two lines of therapy and all having metastatic colorectal cancer with all molecular subtypes. The study is very interesting because it's positive. It has reached its primary endpoint with an improvement in overall survival of 3.3 months as compared to the trifluridine and tipiracil alone when you are using trifluridine and tipiracil with bevacizumab. So the addition of the antiangiogenic drug that is already used in first and second line in patient with RAS mutant colorectal cancer, for example, is adding something new in the third-line setting.
This study is quite important because it succeeded in improving OS, but also in improving progression-free survival, with here, again, something like 3.2 months improvement, and also improving the time to degradation of the performance status of the patient, again, of 3 months. So, all the results are very consistent. It's a major, I would say, step forward in this disease in the third line setting. Of course, 3 months can seem a bit low, but in this setting it's just incredible. No studies to date have ever succeeded to show such an improvement and it will probably dramatically change the sequence of treatment options that we have in this patient.
So, generally, we know what to do in first and second line depending on the molecular status of the disease with many possibilities for first and second line. But in third line, we were, generally, balancing oral drug like trifluridine and tipiracil or regorafenib, or more recently, we have had a positive trial with fruquintinib.
I would say that the SUNLIGHT trial, we changed things because, clearly, the improvement we have here has never been seen before, and I would say that trifluridine and tipiracil plus bevacizumab is going to be the new standard third line, and all other drugs, oral, are going to be moved after this line of treatment to fourth or fifth line of therapy. So it's a practice changing trial. It's very important for our daily practice. In terms of tolerability, it's very good for the patient, because we are seeing the tolerability issues that we are facing with trifluridine and tipiracil with bone marrow, I would say, toxicities and low blood cell counts, et cetera. But globally, there is not an added toxicity with the use of bevacizumab except the classical toxicity of this very well tolerated drug.
Laura A. Dawson, MD, of Canada’s Princess Margaret Cancer Centre, discusses phase III findings from the NRG/RTOG1112 study, which showed that stereotactic body radiation therapy (SBRT) administered prior to sorafenib vs sorafenib alone, improved outcomes in patients with advanced hepatocellular carcinoma. SBRT may become a new standard treatment option for patients with locally advanced disease, especially in the presence of macrovascular invasion (Abstract 489).
Josep Tabernero, MD, PhD, of Spain’s Vall d’Hebron Institute of Oncology, discusses phase III findings from the SUNLIGHT study, which showed that trifluridine and tipiracil (FTD/TPI) plus bevacizumab resulted in improved outcomes compared with FTD/TPI alone in patients with refractory metastatic colorectal cancer. Improvements in survival occurred irrespective of tumor sidedness, RAS mutational status, and receipt of prior bevacizumab. This three-drug regimen may represent a new standard of care for patients whose cancer has progressed after two lines of therapy (Abstract 4).
Manik A. Amin, MD, of Dartmouth Cancer Center, discusses the future of immunotherapy in gastrointestinal cancers, the challenges of creating effective adoptive cell therapies, and the next generation of immune checkpoint inhibitors.
Zev A. Wainberg, MD, of the UCLA School of Medicine, discusses phase III findings from the NAPOLI-3 trial, which showed that first-line NALIRIFOX (liposomal irinotecan plus fluorouracil/leucovorin plus oxaliplatin) improved overall and progression-free survival compared with nab-paclitaxel plus gemcitabine in treatment-naive patients with metastatic pancreatic ductal adenocarcinoma. The safety profile of NALIRIFOX was manageable and consistent with the profiles of each agent (Abstract LBA661).
Filippo Pietrantonio, MD, of Italy’s Istituto Nazionale dei Tumori, discusses phase II results from the INFINITY trial of tremelimumab and durvalumab as neoadjuvant treatment of patients with microsatellite instability–high (MSI) resectable gastric or gastroesophageal junction adenocarcinoma (GAC/GEJAC). These results open the way to investigate nonoperative management in patients with clinical, pathologic, and molecular complete response after T300/D (300 mg of tremelimumab and 1,500 mg every 4 weeks of durvalumab) (Abstract 358).