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SUNLIGHT “is the first phase 3 study in the setting of refractory metastatic colorectal cancer to demonstrate an improvement in overall survival versus an active control,” say the trial investigators. An expert not involved in the study predicted that it will change clinical practice.

The results show that adding bevacizumab to trifluridine (FTD)/tipiracil (TPI) significantly improved survival, compared with those who received FTD/TPI alone. Median overall survival was 10.8 months in the investigational arm vs 7.5 months among controls (hazard ratio, 0.61; P < .001).

Adding bevacizumab also did not increase the risk for serious adverse events or events that led to treatment discontinuation, the researchers noted.

The new data were presented by Josep Tabernero, MD, PhD, head of the department of medical oncology, Vall d’Hebron University Hospital, and director of the Vall d’Hebron Institute of Oncology, Barcelona, at the ASCO Gastrointestinal Cancers Symposium 2023. He concluded that bevacizumab added to FTD/TPI “represents a new standard of care for the treatment of patients with refractory metastatic colorectal cancer who had previously progressed after two lines of therapy.”

Discussant for the abstract, Dustin Deming, MD, an associate professor in the division of hematology, medical oncology and palliative care at the University of Wisconsin–Madison, said the findings showed very “exciting advantages in progression-free and overall survival.” He agreed that “FTD/TPI and bevacizumab should be considered the preferred nontargeted regimen in the refractory setting” and added that “this trial does change standard clinical practice.”

Dr. Deming also said that this has implications for future clinical trials because these results create a new standard for control arms.
 

Improvement in all endpoints

FTD/TPI, which is marketed as Lonsurf, is already approved as a monotherapy for third-line use in refractory metastatic colorectal cancer, and bevacizumab is an established anticancer agent that targets vascular endothelial growth factor and inhibits angiogenesis, he explained. The combination of bevacizumab plus FTD/TPI has previously produced encouraging results in the treatment of refractory metastatic colorectal cancer in smaller phase 2 randomized and single-arm studies.

“The phase 3 SUNLIGHT study was designed to confirm the efficacy and safety of FTD/TPI plus bevacizumab, as compared with FTD/TPI alone, in patients with refractory metastatic colorectal cancer following two chemotherapy regimens,” said Dr. Tabernero.

The cohort included 492 patients who were randomly assigned to receive either FTD/TPI plus bevacizumab (FTD/TPI 35 mg/m2 twice daily on days 1-5 and 8-12 [28-day cycle] and bevacizumab 5 mg/kg on days 1 and 15) or FTD/TPI alone.

Across both arms, most patients (72%) had already received prior treatment with bevacizumab.

At 6 months, the overall survival rate was 77% with the combination therapy versus 61% with the control therapy, and after 12 months, the overall survival rate was 43% versus 30%.

Median progression-free survival was 5.6 months in the treatment arm versus 2.4 months in the control arm (HR, 0.44; P < .001). At 6 months, progression-free survival was 43% versus 16%, respectively, and at 12 months, it was 16% versus 1%.

Both overall response rate and disease control rate were also superior in the investigational arm. The overall response rate was 6.3% versus 0.0% in the control arm, with an absolute gain of 5.4% (P = .004). Similarly, the absolute gain for disease control rate was 29.6% (76.6% vs. 47.0%; P < .001).

For quality of life, worsening in global health status in the investigational arm was significantly delayed, compared with the control arm (8.5 months vs. 4.7 months; HR, 0.50; P < .001), as was worsening to an Eastern Cooperative Oncology Group performance status of 2 or greater (9.3 months vs. 6.3 months; HR, 0.54; P < .001).

When looking at toxicity, Tabernero reported that there were no treatment-related deaths and the rates of severe adverse events were similar in both groups: 72% in the FTD/TPI plus bevacizumab group versus 70% among controls.

“The safety profile was manageable and consistent with the individual safety profiles of FTD/TPI plus bevacizumab,” said Dr. Tabernero.

Overall, adverse events were comparable in both groups, except for slightly higher rates in the bevacizumab plus FTD/TPI arm for hypertension (10% vs. 2%), nausea (37% vs. 27%), and neutropenia (62% vs. 51%).

The study was sponsored by Taiho Oncology, manufacturer of Lonsurf (trifluridine plus tipiracil). Dr. Tabernero and Dr. Deming both reported relationships with numerous pharmaceutical companies. Several of the study authors also reported conflicts of interest.

A version of this article first appeared on Medscape.com.

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SUNLIGHT “is the first phase 3 study in the setting of refractory metastatic colorectal cancer to demonstrate an improvement in overall survival versus an active control,” say the trial investigators. An expert not involved in the study predicted that it will change clinical practice.

The results show that adding bevacizumab to trifluridine (FTD)/tipiracil (TPI) significantly improved survival, compared with those who received FTD/TPI alone. Median overall survival was 10.8 months in the investigational arm vs 7.5 months among controls (hazard ratio, 0.61; P < .001).

Adding bevacizumab also did not increase the risk for serious adverse events or events that led to treatment discontinuation, the researchers noted.

The new data were presented by Josep Tabernero, MD, PhD, head of the department of medical oncology, Vall d’Hebron University Hospital, and director of the Vall d’Hebron Institute of Oncology, Barcelona, at the ASCO Gastrointestinal Cancers Symposium 2023. He concluded that bevacizumab added to FTD/TPI “represents a new standard of care for the treatment of patients with refractory metastatic colorectal cancer who had previously progressed after two lines of therapy.”

Discussant for the abstract, Dustin Deming, MD, an associate professor in the division of hematology, medical oncology and palliative care at the University of Wisconsin–Madison, said the findings showed very “exciting advantages in progression-free and overall survival.” He agreed that “FTD/TPI and bevacizumab should be considered the preferred nontargeted regimen in the refractory setting” and added that “this trial does change standard clinical practice.”

Dr. Deming also said that this has implications for future clinical trials because these results create a new standard for control arms.
 

Improvement in all endpoints

FTD/TPI, which is marketed as Lonsurf, is already approved as a monotherapy for third-line use in refractory metastatic colorectal cancer, and bevacizumab is an established anticancer agent that targets vascular endothelial growth factor and inhibits angiogenesis, he explained. The combination of bevacizumab plus FTD/TPI has previously produced encouraging results in the treatment of refractory metastatic colorectal cancer in smaller phase 2 randomized and single-arm studies.

“The phase 3 SUNLIGHT study was designed to confirm the efficacy and safety of FTD/TPI plus bevacizumab, as compared with FTD/TPI alone, in patients with refractory metastatic colorectal cancer following two chemotherapy regimens,” said Dr. Tabernero.

The cohort included 492 patients who were randomly assigned to receive either FTD/TPI plus bevacizumab (FTD/TPI 35 mg/m2 twice daily on days 1-5 and 8-12 [28-day cycle] and bevacizumab 5 mg/kg on days 1 and 15) or FTD/TPI alone.

Across both arms, most patients (72%) had already received prior treatment with bevacizumab.

At 6 months, the overall survival rate was 77% with the combination therapy versus 61% with the control therapy, and after 12 months, the overall survival rate was 43% versus 30%.

Median progression-free survival was 5.6 months in the treatment arm versus 2.4 months in the control arm (HR, 0.44; P < .001). At 6 months, progression-free survival was 43% versus 16%, respectively, and at 12 months, it was 16% versus 1%.

Both overall response rate and disease control rate were also superior in the investigational arm. The overall response rate was 6.3% versus 0.0% in the control arm, with an absolute gain of 5.4% (P = .004). Similarly, the absolute gain for disease control rate was 29.6% (76.6% vs. 47.0%; P < .001).

For quality of life, worsening in global health status in the investigational arm was significantly delayed, compared with the control arm (8.5 months vs. 4.7 months; HR, 0.50; P < .001), as was worsening to an Eastern Cooperative Oncology Group performance status of 2 or greater (9.3 months vs. 6.3 months; HR, 0.54; P < .001).

When looking at toxicity, Tabernero reported that there were no treatment-related deaths and the rates of severe adverse events were similar in both groups: 72% in the FTD/TPI plus bevacizumab group versus 70% among controls.

“The safety profile was manageable and consistent with the individual safety profiles of FTD/TPI plus bevacizumab,” said Dr. Tabernero.

Overall, adverse events were comparable in both groups, except for slightly higher rates in the bevacizumab plus FTD/TPI arm for hypertension (10% vs. 2%), nausea (37% vs. 27%), and neutropenia (62% vs. 51%).

The study was sponsored by Taiho Oncology, manufacturer of Lonsurf (trifluridine plus tipiracil). Dr. Tabernero and Dr. Deming both reported relationships with numerous pharmaceutical companies. Several of the study authors also reported conflicts of interest.

A version of this article first appeared on Medscape.com.

SUNLIGHT “is the first phase 3 study in the setting of refractory metastatic colorectal cancer to demonstrate an improvement in overall survival versus an active control,” say the trial investigators. An expert not involved in the study predicted that it will change clinical practice.

The results show that adding bevacizumab to trifluridine (FTD)/tipiracil (TPI) significantly improved survival, compared with those who received FTD/TPI alone. Median overall survival was 10.8 months in the investigational arm vs 7.5 months among controls (hazard ratio, 0.61; P < .001).

Adding bevacizumab also did not increase the risk for serious adverse events or events that led to treatment discontinuation, the researchers noted.

The new data were presented by Josep Tabernero, MD, PhD, head of the department of medical oncology, Vall d’Hebron University Hospital, and director of the Vall d’Hebron Institute of Oncology, Barcelona, at the ASCO Gastrointestinal Cancers Symposium 2023. He concluded that bevacizumab added to FTD/TPI “represents a new standard of care for the treatment of patients with refractory metastatic colorectal cancer who had previously progressed after two lines of therapy.”

Discussant for the abstract, Dustin Deming, MD, an associate professor in the division of hematology, medical oncology and palliative care at the University of Wisconsin–Madison, said the findings showed very “exciting advantages in progression-free and overall survival.” He agreed that “FTD/TPI and bevacizumab should be considered the preferred nontargeted regimen in the refractory setting” and added that “this trial does change standard clinical practice.”

Dr. Deming also said that this has implications for future clinical trials because these results create a new standard for control arms.
 

Improvement in all endpoints

FTD/TPI, which is marketed as Lonsurf, is already approved as a monotherapy for third-line use in refractory metastatic colorectal cancer, and bevacizumab is an established anticancer agent that targets vascular endothelial growth factor and inhibits angiogenesis, he explained. The combination of bevacizumab plus FTD/TPI has previously produced encouraging results in the treatment of refractory metastatic colorectal cancer in smaller phase 2 randomized and single-arm studies.

“The phase 3 SUNLIGHT study was designed to confirm the efficacy and safety of FTD/TPI plus bevacizumab, as compared with FTD/TPI alone, in patients with refractory metastatic colorectal cancer following two chemotherapy regimens,” said Dr. Tabernero.

The cohort included 492 patients who were randomly assigned to receive either FTD/TPI plus bevacizumab (FTD/TPI 35 mg/m2 twice daily on days 1-5 and 8-12 [28-day cycle] and bevacizumab 5 mg/kg on days 1 and 15) or FTD/TPI alone.

Across both arms, most patients (72%) had already received prior treatment with bevacizumab.

At 6 months, the overall survival rate was 77% with the combination therapy versus 61% with the control therapy, and after 12 months, the overall survival rate was 43% versus 30%.

Median progression-free survival was 5.6 months in the treatment arm versus 2.4 months in the control arm (HR, 0.44; P < .001). At 6 months, progression-free survival was 43% versus 16%, respectively, and at 12 months, it was 16% versus 1%.

Both overall response rate and disease control rate were also superior in the investigational arm. The overall response rate was 6.3% versus 0.0% in the control arm, with an absolute gain of 5.4% (P = .004). Similarly, the absolute gain for disease control rate was 29.6% (76.6% vs. 47.0%; P < .001).

For quality of life, worsening in global health status in the investigational arm was significantly delayed, compared with the control arm (8.5 months vs. 4.7 months; HR, 0.50; P < .001), as was worsening to an Eastern Cooperative Oncology Group performance status of 2 or greater (9.3 months vs. 6.3 months; HR, 0.54; P < .001).

When looking at toxicity, Tabernero reported that there were no treatment-related deaths and the rates of severe adverse events were similar in both groups: 72% in the FTD/TPI plus bevacizumab group versus 70% among controls.

“The safety profile was manageable and consistent with the individual safety profiles of FTD/TPI plus bevacizumab,” said Dr. Tabernero.

Overall, adverse events were comparable in both groups, except for slightly higher rates in the bevacizumab plus FTD/TPI arm for hypertension (10% vs. 2%), nausea (37% vs. 27%), and neutropenia (62% vs. 51%).

The study was sponsored by Taiho Oncology, manufacturer of Lonsurf (trifluridine plus tipiracil). Dr. Tabernero and Dr. Deming both reported relationships with numerous pharmaceutical companies. Several of the study authors also reported conflicts of interest.

A version of this article first appeared on Medscape.com.

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