Josep Tabernero, MD, PhD, head of the Medical Oncology Department, the Vall d'Hebron University Hospital, director, the Vall d'Hebron Institute of Oncology (VHIO), discusses findings from the phase 3 SUNLIGHT trial (NCT04737187) investigating the combination of bevacizumab (Avastin) plus trifluridine/tipiracil (TAS-102; Lonsurf) vs TAS-102 alone in patients with refractory metastatic colorectal cancer (mCRC).

Data presented at the 2023 Gastrointestinal Cancers Symposium showed that the study met its primary end point with a statistically significant and a clinically meaningful improvement in overall survival (OS). Patients treated with bevacizumab/TAS-102 experienced a median OS of 10.8 months, compared with 7.5 months for patients treated with TAS-102 alone, representing a 39% reduction in the risk of death (HR, 0.61; 95% CI, 0.49-0.77; 

Additional study end points, including progression-free survival (PFS), time to deterioration in global-health status, and time to deterioration of ECOG performance status to 2 or higher, also favored bevacizumab/TAS-102, Tabernero explains. Notably, there was a statistically significant improvement in PFS, with bevacizumab/TAS-102 eliciting a median PFS of 5.6 months, compared with 2.4 months for TAS-102 alone (HR, 0.44; 95% CI, 0.36-0.54; 

The emergence of novel first- and second-line therapies for patients with mCRC has led to an increase in patients in the refractory setting, according to Tabernero, who notes that new combinations could help address unmet needs for patients with refractory mCRC.

SUNLIGHT enrolled 492 patients with refractory mCRC following 2 chemotherapy regimens. They were randomly assigned in a 1:1 fashion to receive bevacizumab plus TAS-102 or TAS-102 monotherapy.

Regarding safety, severe adverse effects (AEs) of grade 3 or higher occurred in 72.4% of patients in the bevacizumab/TAS-102 arm, compared with 69.5% in the TAS-102 arm. The most frequent severe treatment-emergent AEs for bevacizumab/TAS-102 and TAS-102 alone were neutropenia (43.1% and 32.1%, respectively) and anemia (6.1% and 11.0%).

Based on this data, bevacizumab plus TAS-102 may be another standard of care for patients with refractory mCRC, Tabernero concludes.

Videos

Josep Tabernero, MD, PhD, discusses findings from the phase 3 SUNLIGHT trial investigating the combination of bevacizumab plus trifluridine/tipiracil vs TAS-102 alone in patients with refractory metastatic colorectal cancer.

Dr. Tabernero on the Efficacy of Bevacizumab Plus TAS-102 in Refractory mCRC

Josep Tabernero, MD, PhD, head, Medical Oncology Department, Vall d’Hebron University Hospital, director, Vall d’Hebron Institute of Oncology, discusses his opinions on which patients with metastatic colorectal cancer should receive ziv-aflibercept following bevacizumab.

Tabernero says the right answer to this is still unknown. In the VELOUR trial, only one-third of the patients had previously received bevacizumab, which means researchers only have a small population of patients to draw conclusions from.

Taking this into consideration, Tabernero says the data looks good for patients who received prior bevacizumab and also for patients who continue bevacizumab, according to the TML trial. However, the population from the TML trial is not completely comparable to the population in the VELOUR trial, Tabernero warns, and he suggests having a head-to-head comparison.

Since PFS and OS are hard to compare, Tabernero suggests comparing the response rates of the two trials. In the VELOUR trial, the combination of aflibercept and FOLFIRI had a better response rate than FOLFIRI alone. The increase of response rate that was seen in the VELOUR trial was greater than the increase in the response rate that was seen in the TML trial.

View more from the 2014 World GI Congress

Josep Tabernero, MD, PhD, head, Medical Oncology Department, Vall d'Hebron University Hospital, director, Vall d'Hebron Institute of Oncology, discusses his opinions on which patients with metastatic colorectal cancer should receive aflibercept following bevacizumab.

Dr. Tabernero on Sequencing Angiogenesis Inhibitors in mCRC

Josep Tabernero, MD, PhD, of Vall d’Hebron University Hospital, Barcelona, discusses new characterizations of colorectal cancer.

Tabernero says physicians have been working on two important colorectal cancer characterizations over the year. While physicians were aware that 

 mutations played a role as a narrative primitive biomarker for patients with colorectal cancer, Tabernero says, physicians have now discovered that 

 mutations are important narrative primitive factors. Tabernero says that this discovery will allow physicians to focus more on a selective population of patients that will benefit more from EGFR treatments.

Physicians have also made new discoveries concerning 

 mutated colorectal cancers, which accounts for 5-10% of patients with colorectal cancer, Tabernero says.

Tabernero says physicians are developing important treatment strategies by combining BRAF V600E inhibitor with EGFR inhibitors and other pathway inhibitors. Studies are currently underway to test different treatment strategies in this pathway. More and more, physicians are characterizing different populations of colorectal cancer, Tabernero says, to try to provide these patients with the best treatment options. 

Josep Tabernero, MD, PhD, of Vall d'Hebron University Hospital, Barcelona, discusses new characterizations of colorectal cancer.

Dr. Tabernero on New Characterizations in CRC

Josep Tabernero, MD, PhD, of Vall d’Hebron University Hospital, Barcelona, believes that in order to treat patients with gastrointestinal cancers more effectively, researchers must focus on the molecular classification of particular subpopulations.  

Defining unique subtypes within broad tumor classes will help researchers discover key underlying molecular drivers, Tabernero states. Once discovered, these molecular classifications will aid the development of focused targeted agents for patients with advanced malignancies. 

Initially, Tabernero believes, the application of these unique molecular characterizations, gene profiles, and expressed proteins will apply mostly to advanced disease. However, they will be translated into earlier stages through the introduction of new treatment options. These targeted treatment approaches, Tabernero states, will result in better treatment outcomes than conventional therapies. 

Josep Tabernero, MD, PhD, from the Vall d'Hebron University Hospital, believes that in order to treat patients with gastrointestinal cancers more effectively, researchers must focus on the molecular classification of particular subpopulations.  

Josep Tabernero, MD, PhD

Articles

Dr. Tabernero on the Efficacy of Bevacizumab Plus TAS-102 in Refractory mCRC

Dr. Tabernero on Sequencing Angiogenesis Inhibitors in mCRC

Dr. Tabernero on New Characterizations in CRC

Dr. Tabernero on Molecular Characterization in GI Cancer