Oncology Data Advisor: Welcome to Oncology Data Advisor, I'm Keira Smith. Today I'm joined by Dr. Tabernero, who is here to talk about the results of the phase 3 SUNLIGHT trial being presented at the ASCO Gastrointestinal (GI) Cancers Symposium. Dr. Tabernero, thanks so much for joining me today.

Josep Tabernero, MD, PhD: Absolutely. My name is Josep Tabernero. I'm a Medical Oncologist based in Barcelona at the Vall d'Hebron Institute of Oncology. My special focus has been always the treatment of patients with GI malignancies and early drug development.

Oncology Data Advisor: Would you like to share these results of the SUNLIGHT trial that your presenting, and their significance?

Dr. Tabernero: Absolutely, so the SUNLIGHT trial is actually the first study that shows improvement in efficacy over an existing active treatment in patients with refractory metastatic colorectal cancer. The magnitude of the benefit that has been observed is greater than in other trials and in a particular population that is refractory to previous lines of therapy. That includes all the available cytotoxic agents and biological agents, so all patients have been treated with a fluoropyrimidine, with irinotecan, with oxaliplatin, and with either an anti–vascular endothelial growth factor (VEGF) therapy and/or an anti–epidermal growth factor receptor (EGFR) therapy. They are what we clearly call refractory.

The study validates the clinical activity of trifluridine/tipiracil plus bevacizumab in patients in this situation. Basically, in the study, we have seen that the median overall survival has improved by 3.3 months. This is not only statistically significant, but clinically relevant, favoring the combination of trifluridine/tipiracil plus bevacizumab over trifluridine/tipiracil alone. The median survival in the trifluridine/tipiracil arm was 7.5 months, and this went up to 10.8 months in the combination regimen. This was statistically significant, with a P value of less than 0.001 and a hazard ratio that is very impressive, 0.61.

All the other efficacy parameters that we look for, including progression-free survival, overall response rate, disease control rate, and time to deterioration of the performance status to Eastern Cooperative Oncology Group (ECOG) 2 or more, were statistically significant and clinically meaningful favoring the experimental arm as well. In thinking of the safety profile, the treatment was actually very tolerable.

The percentage of patients who had grade 3 or 4 adverse events or serious adverse events was the same in the two arms. The only adverse events that were slightly more frequent in the combination arm were hypertension, nausea, and neutropenia, but neutropenia did not translate into febrile neutropenia. Globally, I think that the safety profile of the combination is really very good.

In my opinion, there's going to be a new standard of care in this refractory setting. The improvement of more than three months in overall survival with the treatment that's administered in the refractory setting is clinically meaningful for most of the guidelines and even for most of the payers.

Oncology Data Advisor: How do you think this will fit into the treatment landscape for metastatic colorectal cancer?

Dr. Tabernero: Well, the National Comprehensive Cancer Network (NCCN) guidelines are already recommending trifluridine/tipiracil plus bevacizumab in the refractory setting. This is because a previously published randomized phase 2 study suggested an advantage in overall survival. Now we have a formalization of that because this is a phase 3 study with almost 500 patients included. As mentioned, all the different end points that we looked for were statistically significant favoring the combination, all of them with a P value of less than 0.001. It's remarkable.

My perception is that this is going to be very rapidly incorporated into all the professional societies' clinical guidelines. I hope that the regulatory agencies also approve the label of this combination. I think that this is going to go quite fast, because both drugs, trifluridine/tipiracil and bevacizumab, are already approved for the treatment of metastatic colorectal cancer. I don't see, in principle, any reason why there should be a delay in the labeling of the combination.

Oncology Data Advisor: That's really exciting. Anything else you'd like to share, either about the trial or about anything else from the symposium? 

Dr. Tabernero: About the trial, something else to mention, number one, is that this is an international multicenter trial. The population is global and homogenous, but at the same time, it provides the efficacy view of patients being included all around the world. Number two, I think that it's also important to mention that in looking at the forest plot analysis for potential predictive factors that would define any subgroup of patients that did not benefit from the addition of bevacizumab to trifluridine/tipiracil, we were unable to find any subgroup of patients that did not benefit from the addition of bevacizumab. This is the kind of study where you sometimes see that some subgroups of patients do not benefit as well, but that is not the case in this particular trial.

About ASCO, I am very happy, because this is the twentieth anniversary of our GI-focused meeting sponsored by ASCO. This is an important milestone, and I would like to congratulate ASCO. In this particular year, we have many exciting new data not only in the field of colorectal cancer but also in the fields of gastroesophageal cancer, pancreatic cancer, and hepatocellular carcinoma. Some of these data are practice-changing, so I'm really very happy about this year's meeting.

Oncology Data Advisor: That'll be really exciting to see all the other data too. Well, thanks so much for sharing all this today. I really appreciate it.

Dr. Tabernero: My pleasure.

About Dr. Tabernero

Josep Tabernero, MD, PhD, is the Head of the Medical Oncology Department at the Vall d'Hebron Barcelona Hospital Campus and the Director of the Vall d'Hebron Institute of Oncology in Barcelona, Spain. He focuses on gastrointestinal cancer research, particularly on the development of molecular targeted therapies, novel chemotherapeutics, and immunotherapies. Dr. Tabernero served as the President of the European Society for Medical Oncology (ESMO) from 2018 to 2019, and he is currently a member of many scientific committees for ESMO, ASCO, and other professional societies. He has authored approximately 450 peer-reviewed publications.

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Transcript edited for clarity. Any views expressed above are the speaker's own and do not necessarily reflect those of Oncology Data Advisor.