Julien Taieb, MD, PhD, head, the Gastroenterology and Gastrointestinal Oncology Department, the Georges Pompidou European Hospital, Université de Paris, discusses the significance of the FDA approval of trifluridine/tipiracil (TAS-102; Lonsurf) plus bevacizumab (Avastin) in patients with pretreated metastatic colorectal cancer (mCRC).

FDA approved the combination of TAS-102 and bevacizumab

 in patients with previously treated mCRC. The regulatory decision was based on findings from the phase 3 SUNLIGHT trial (NCT04737187), which included 492 patients who had received up to 2 prior chemotherapy regimens. Overall survival (OS) and progression-free survival (PFS) served as the coprimary end points of the trial.

In this trial, the combination elicited a statistically significant improvement in OS vs TAS-102 alone (HR, 0.61; 95% CI, 0.49-0.77; 1-sided 

 < .001). The median OS was 10.8 months (95% CI, 9.4-11.8) in patients who received the combination compared with 7.5 months (95% CI, 6.3-8.6) in those who received TAS-102 alone. In addition, the median PFS was 5.6 months (95% CI, 4.5-5.9) in the combination arm vs 2.4 months (95% CI, 2.1-3.2) in the TAS-102 monotherapy arm (HR, 0.44; 95% CI, 0.36-0.54; 1-sided 

The most common adverse effects or laboratory abnormalities experienced by patients who received the combination were neutropenia, thrombocytopenia, anemia, nausea, fatigue, increased alanine aminotransferase, increased aspartate aminotransferase, decreased sodium, increased alkaline phosphatase, abdominal pain, decreased appetite, and diarrhea.

The FDA approval of TAS-102 plus bevacizumab is important because it demonstrates the validity of combining 2 agents with known efficacy in patients with mCRC, Taieb says. The synergy between TAS-102 and bevacizumab is good and will be practice changing in the United States and potentially worldwide, Taieb emphasizes. Based on the results of the SUNLIGHT trial, this combination can be used as a standard third-line treatment for patients with mCRC, Taieb concludes.

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Dr Taieb on the FDA Approval of TAS-102 Plus Bevacizumab in mCRC

Julien Taieb, MD, PhD, professor of medicine, Université Paris Cité, The Hôpital Européen Georges-Pompidou, Université de Paris, discusses the safety profile associated with trifluridine/tipiracil (TAS-102; Lonsurf) with bevacizumab (Avastin) in refractory metastatic colorectal cancer (mCRC).

At the 2023 ASCO Annual Meeting, Taieb and colleagues presented data from a post-hoc analysis of the phase 3 SUNLIGHT trial (NCT04737187), showing that TAS-102 plus bevacizumab prolonged overall survival (OS) in patients with mCRC in patients who maintained their ECOG performance status compared with TAS-102 alone. Notably, these results were consistent with what was previously reported in the intent-to-treat population. 

Previous efficacy and safety data from the phase 3 trial presented at the 2023 Gastrointestinal Cancers Symposium

 showed that the median OS was improved with the addition of bevacizumab to TAS-102 (10.8 months) vs TAS-102 alone (7.5 months; HR, 0.61; 95% CI, 0.49-0.77; 

Although TAS-102 is associated with low clinical toxicities, hematological toxicities can be a concern, Taieb says. One of the primary adverse effects associated with TAS-102 is neutropenia, which can create issues when attempting to continue the treatment regimen, Taieb explains. However, from a patient perspective, they may not necessarily be aware that their white blood cells are low, making it important to monitor, he adds, noting that granulocyte colony–stimulating factor could be used to combat instances of neutropenia. In the previously reported data from SUNLIGHT, the rates of any-grade neutropenia were 62% in the combination arm vs 51% for TAS-102 alone.

When adding bevacizumab to treatment with TAS-102, it is important to be aware of the AEs associated with bevacizumab; however, this is also a generally well-tolerated drug, Taieb emphasizes. The main AE associated with bevacizumab is hypertension; however, in rare cases, proteinuria may be observed, he concludes.

Julien Taieb, MD, PhD, discusses the safety profile associated with trifluridine/tipiracil with bevacizumab in refractory metastatic colorectal cancer.

Dr Taieb on the Safety Proline of TAS-102/Bevacizumab in Refractory mCRC

Julien Taieb, MD, PhD, professor of medicine, Université Paris Cité, The Hôpital Européen Georges-Pompidou, Université de Paris, discusses key findings from a post-hoc analysis of the phase 3 SUNLIGHT trial (NCT04737187) of combination of trifluridine/tipiracil (TAS-102; Lonsurf) with bevacizumab (Avastin) in patients with refractory metastatic colorectal cancer (mCRC).

Data from a post-hoc analysis presented at the 2023 ASCO Annual Meeting indicated that TAS-102 plus bevacizumab prolonged overall survival (OS) vs TAS-102 alone in patients who maintained their ECOG performance status. These results were consistent with what was previously reported in the overall study population, Taieb says. In the post-hoc analysis, patients with maintained ECOG performance status treated with the combination experienced a median OS of 10.58 months vs 8.71 months for those given TAS-102 alone (HR, 0.78; 95% CI, 0.61-0.99).

investigators had previously presented data from the phase 3 trial at the 2023 Gastrointestinal Cancers Symposium

, which showed that median OS was improved with the addition of bevacizumab to TAS-102 (10.8 months) vs TAS-102 alone (7.5 months; HR, 0.61; 95% CI, 0.49-0.77; 

 < .001). Taieb notes that this 3.3-month improvement was not expected in a such a heavily pretreated patient population.

Prior data from the overall population showed that the median progression-free survival (PFS) was 5.6 months in the experimental arm vs 2.4 months in the control arm (HR, 0.61; 95% CI, 0.49-0.77; 

 < .001). In the post-hoc analysis, patients who maintained an ECOG performance status of 0 or 1 experienced a median PFS of 5.22 months with TAS-102 plus bevacizumab vs 2.55 months for TAS-102 alone (HR, 0.49; 95% CI, 0.40-0.61).

Notably, the median time to worsening of ECOG performance status was 9.3 months in the TAS-102/bevacizumab arm compared with 6.3 months in the TAS-102 arm (HR, 0.54; 95% CI, 0.43-0.67; 

Julien Taieb, MD, PhD, discusses key findings from a post-hoc analysis of the phase 3 SUNLIGHT trial of combination of trifluridine/tipiracil with bevacizumab in patients with refractory metastatic colorectal cancer.


Dr Taieb on Findings from a Post-hoc Analysis of TAS-102 Plus Bevacizumab in Refractory mCRC

Julien Taieb, MD, head of the gastroenterology and gastrointestinal oncology department of the Georges Pompidou European Hospital, Paris Descartes University, discusses sidedness in metastatic colon cancer.

Taieb states that disease-free survival with no recurrence is not impacted by sidedness. Conversely, if a patient relapses, the survival after relapse is clearly impacted by sidedness with right-sided tumors having a poorer prognosis.

 mutant, it seems that having a right-sided tumor is a good prognostic factor, Taieb adds.

Dr. Taieb Discusses Sidedness in Metastatic Colon Cancer

Julien Taieb, MD, head of the gastroenterology and gastrointestinal oncology department of the Georges Pompidou European Hospital, Paris Descartes University, discusses primary tumor location in colorectal cancer (CRC).

There has been a big buzz around primary tumor location in CRC, with right-sided tumors being associated with poorer outcomes than left-sided tumors.

Additionally, the field is at a time of molecular classification, says Taieb, and finding predictive biomarkers is critical. 

Julien Taieb, MD, head of the gastroenterology and gastrointestinal oncology department of the Georges Pompidou European Hospital, Paris Descartes University, discusses primary tumor location in colorectal cancer.

Julien Taieb, MD, PhD

Articles

Dr Taieb on the FDA Approval of TAS-102 Plus Bevacizumab in mCRC

Dr Taieb on the Safety Proline of TAS-102/Bevacizumab in Refractory mCRC

Dr Taieb on Findings from a Post-hoc Analysis of TAS-102 Plus Bevacizumab in Refractory mCRC

Dr. Taieb Discusses Sidedness in Metastatic Colon Cancer

Dr. Taieb Discusses Primary Tumor Location in CRC