Adding Avastin to Lonsurf Improved Outcomes in Pretreated Colorectal Cancer


Patients with pretreated metastatic colorectal cancer had better outcomes when Avastin was added to their Lonsurf treatment in the third line setting.

Previously treated patients with metastatic colorectal cancer tended to live longer and have better disease control when administered third-line Avastin (bevacizumab) plus Lonsurf (trifluridine/tipiracil; TAS-102) compared to those who were given Lonsurf alone, according to findings from the phase 3 SUNLIGHT trial.

Average overall survival, which is defined as the time from treatment until death of any cause, was 10.8 months in the Avastin/Lonsurf group and 7.5 months in the control (Lonsurf alone) arm. At six months, the overall survival rate was 77% compared to 61%, respectively, and at 12 months, the overall survival rate was 43% and 30%, respectively.

“The SUNLIGHT study 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,” Dr. Josep Tabernero, head, Department of Medical Oncology, Vall d’Hebron University Hospital, and director, Vall d’Hebron Institute of Oncology in Barcelona, Spain, said during the presentation of study data at the 2023 American Society of Clinical Oncology Gastrointestinal Cancers Symposium.

The study evaluated 492 patients with metastatic colorectal cancer who had been previously treated with fluoropyrimidine, irinotecan, oxaliplatin, an anti-VEGF monoclonal antibody (not necessarily Avastin), and/or an anti-EGFR monoclonal antibody in those patients whose tumor harbored a RAS mutation.

Patients were divided by geographic region (North America, the European Union or the rest of the world); time since diagnosis of first metastasis (less than 18 or 18 months or longer); and RAS status (wild-type or mutant). Participants were randomly assigned to receive either a regimen containing Avastin and Lonsurf (246 patients) or Lonsurf alone (246 patients).

The main goal of the trial was overall survival and secondary endpoints included progression-free survival (time from treatment until disease gets worse), disease control rate and safety.

“Seventy percent of patients in the treatment arm had RAS mutant status compared with 69% in the control arm, demonstrating an unmet need,” Tabernero said. Across both arms, prior treatment with Avastin was equal (72%).

When determining overall survival benefit by prespecified subgroup, the investigators noted that their analysis revealed that all subgroups benefited from the addition of Avastin, and in particular, patients who had not been previously treated with Avastin demonstrated greater benefit with the addition of the agent to Lonsurf.

The average progression-free survival was 5.6 months in the Avastin-Lonsurf group and 2.4 months in the control arm. The six-month progression-free survival rate was 43% versus 16%, respectively, and the 12-month rate was 16% vs 1%, respectively. Tabernero said a progression-free survival analysis by prespecified subgroup showed similar findings as the overall survival subgroup analysis, with all subgroups showing benefit.

“Both overall response rate and disease control rate was superior for the (Avastin-containing) arm in patients who were evaluable for tumor response,” Tabernero said. “The absolute gain for overall response rate was 5.4% and the absolute gain for disease control rate was 29.6%.”

Turning to quality-of-life characteristics, the median time to deterioration in global health status in the treatment arm was 8.5 months compared to 4.7 months in the control arm.

Similarly, the time to worsening to an ECOG performance status of 2 — meaning that patients are able to perform self-care tasks, but not work — or greater (worsening status) was statistically superior for patients receiving Lonsurf with Avastin (9.3 months) compared to Lonsurf alone (6.3 months).

“In looking at parameters related to quality of life, both worsening of the baseline global health status and ECOG performance status from zero or 1 to 2 or more was significantly delayed in patients who received Lonsurf plus Avastin compared with Lonsurf alone,” Tabernero said.

Regarding safety, overall side effects were equally reported for both arms.

Investigators reported zero treatment-related deaths, rates of severe side effects were 72% in the treatment arm and 70% in the control arm, and 13% of patients in both arms experienced side effects leading to withdrawal from the study.

Sixteen percent of patients in the treatment arm experienced dose reductions compared to 12% in the control arm. The percentage of dose delays was higher in the treatment arm (70%) versus the control arm (53%).

Treatment-emergent side effects were comparable in the two groups, although Tabernero noted that high blood pressure was higher in the treatment arm (10% vs 2%), and that nausea (37% vs 27%) and neutropenia (62% vs 51%) were more common in the treatment arm.

“Only one patient in the experimental arm experienced febrile neutropenia, compared to six patients in the control arm,” Tabernero said.

“To conclude, the combination of Lonsurf plus Avastin represents a new standard of care for the treatment of patients with refractory metastatic CRC who had previously progressed after two lines of therapy,” Tabernero said.

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