Sequence effect for third-line treatment of mCRC

For patients with metastatic colorectal cancer (mCRC) whose cancer progressed despite 2 lines of chemotherapy, treatment with trifluridine/tipiracil followed by regorafenib is a better option than treatment with regorafenib followed by trifluridine/tipiracil, results from the phase 2 SOREGATT trial showed.

Until recently, only 2 treatment options were available for patients with mCRC whose cancer progressed despite 2 lines of chemotherapy: regorafenib or trifluridine/tipiracil. Both treatment options showed comparable efficacy in phase 3 studies against placebo.

The phase 2 SOREGATT trial (NCT04450836) was designed to investigate the optimal sequence of regorafinib and trifluridine/tipiracil. The primary endpoint was the feasibility of the treatment sequences, i.e. the percentage of participants treated with at least 2 cycles of both regorafenib and trifluridine/tipiracil. Prof. Michel Ducreux (Gustave Roussy, France) presented the results [1].

The study meant to randomise 340 participants who failed on 2 lines of chemotherapy 1:1 to regorafenib followed by trifluridine/tipiracil (Arm A) or trifluridine/tipiracil followed by regorafenib (Arm B). However, enrolment was prematurely stopped after presentation of the results of the SUNLIGHT trial demonstrating superior efficacy of trifluridine/tipiracil plus bevacizumab over trifluridine/tipiracil alone [2]. Eventually, 231 participants were randomised and treated in the SOREGATT trial.

In Arm A of SOREGATT, 40% of the participants were treated with at least 2 cycles of both treatment regimens, in Arm B this was 55.5% (P=0.018). The main reasons to end the first treatment were disease progression (80.4% in Arm A; 90.8% in Arm B) and toxicity (14.3% in Arm A; 7.6% in Arm B). No significant difference was observed between both study arms in median overall survival (6.0 vs 6.9 months; P=0.3) nor median progression-free survival (1.87 vs 1.97 months; P=0.10). A trend of a better outcome in Arm B was observed for PFS2 (the time interval from randomisation until death or disease progression observed in the second sequence of treatment): 26.9% at 6 months in Arm B versus 16.1% in Arm A. In addition, time to failure was longer in Arm B: 22.7% non-failure in Arm B after 6 months versus 12.2% non-failure in Arm A.

Despite the premature termination of the study due to the publication of data from the SUNLIGHT study, this study provides important information, Prof. Ducreux concluded. “There is indeed a sequence effect, and starting with trifluridine/tipiracil clearly appears to be a better strategy. However, the median overall survival of these patients remains short: around 6 to 7 months.”

1. Ducreux MP, et al. PRODIGE 68 - UCGI 38 - SOREGATT: A randomized phase 2 study comparing the sequences of regorafenib (reg) and trifluridine/tipiracil (t/t) after failure of standard therapies in patients (pts) with metastatic colorectal cancer (mCRC). Abstract 3O, ESMO Gastrointestinal Cancers Congress 2024, 26–29 June, Munich, Germany.
2. Prager GW, et al. N Engl J Med 2023;388:1657-1667.

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Posted on 21 August 202421 August 2024