Consistent benefits and safety were seen with TAS-102 (trifluridine/tipiracil; Lonsurf) in a real-world treatment setting for patients with refractory metastatic colorectal cancer, according to preliminary data from the phase IIIb open-label PRECONNECT trial.
Alfredo Falcone, MD
Consistent benefits and safety were seen with TAS-102 (trifluridine/tipiracil; Lonsurf) in a real-world treatment setting for patients with refractory metastatic colorectal cancer (mCRC), according to preliminary data from the phase IIIb open-label PRECONNECT trial.
In findings from the ongoing study, presented at the 2018 World Congress on GI Cancer,1the investigator-assessed median progression-free survival (PFS) with TAS-102 was 2.8 months (95% CI, 2.7-3.3). The objective response rate (ORR) was 2.4% (95% CI, 1.2%-4.2%) and the disease control rate was 36.8% (95% CI, 32.4%-41.4%). The median time to deterioration to ECOG performance status ≥2 was 8.7 months (range, 0.2-11.0).
Findings from the PRECONNECT study, which enrolled primarily in Europe, were in alignment with the pivotal phase III RECOURSE study, which led to approval for the medication in the United States, Japan, and more than 48 countries throughout Europe and Asia. In this study,2the median overall survival for patients with mCRC who received TAS-102 was 7.2 months compared with 5.2 months with placebo (HR, 0.69;P<.0001). Median PFS in the TAS-102 arm was 2.0 months versus 1.7 months with placebo (HR, 0.48;P<.0001). The ORR was 1.6% for TAS-102 compared with 0.4% for placebo.
“These are the first data reported on the widespread use of trifluridine/tipiracil in the clinical setting outside of the United States and Japan. The safety and efficacy results of this interim analysis are consistent with that in the RECOURSE randomized controlled trial,” said lead investigator Alfredo Falcone, MD, of the University of Pisa in Pisa, Italy.
Due to the descriptive nature of the study, no formal calculation of sample size or formal statistical testing was conducted or planned, including an assessment of overall survival. “However, I am sure that overall survival will be retrospectively analyzed,” Falcone remarked. “The study aims to assess the safety and efficacy of trifluridine/tipiracil in daily practice, but also to provide early access to this drug for eligible adult patients with metastatic colorectal cancer,” he said.
Between October 2016 and May 2017, the ongoing PRECONNECT study enrolled and provided at least 1 dose of TAS-102 to 462 patients. Patients were treated with oral TAS-102 at 35 mg/m2twice daily on days 1 through 5 and 8 through 12 in 28-day cycles. Treatment was continued until disease progression, unacceptable toxicity, or commercial availability of the study drug.
The median age of patients was 64 years (range, 28-87) and 63.6% were male. Fifty-four percent of patients had ECOG performance status of 1; more than 97% of patients had received prior fluoropyrimidine, oxaliplatin, or irinotecan and 96.3% received combined oxaliplatin and irinotecan. Other prior treatments included anti-VEGF therapy (83.9%), anti-EGFR therapy (41.5%), and regorafenib (35.7%). The remaining 16.7% of patients had received other therapies.
The primary tumor site was in the right colon for 24.4% of patients and 51.9% of patients had synchronous metastases at diagnosis.RASmutations were reported for 52.1% of patients and 2.6% hadBRAFmutations.
Of the 462 patients with treatment exposure, 77.3% had withdrawn due to disease progression at the November 2017 data cut-off. There had been 40 deaths.
After a minimum of 5 months of follow-up, the median treatment duration was 3 months (range, 0.5-11.0) and patients had received a median of 3 cycles (range, 1-12). Treatment discontinuation due to adverse events (AEs) was low. “Just 2.2% of patients withdrew from the study due to treatment-related adverse events,” Falcone noted. Dose reductions due to AEs were necessary in just 8% of patients. “The median relative dose intensity was high, at 89%,” Falcone said.
AEs of all grades occurred in 92.6% of patients and grade ≥3 AEs were seen in 72.5% of patients; the most commonly reported grade ≥3 AEs were neutropenia in 39.3% of patients, anemia in 11.8%, and diarrhea (5.2%). Febrile neutropenia was experienced by 1.7% of patients.
“These PRECONNECT data provide further support of trifluridine/tipriracil as a safe and efficacious treatment for pretreated mCRC patients,” Falcone said.
Overall, 793 patients had been enrolled in PRECONNECT as of May 2018 and final enrollment of 1000 patients is planned. “Preliminary quality of life results and subgroup analyses are anticipated for upcoming congresses and the final results are expected in 2020,” said Falcone.