Regorafenib (Reg) As A Single Agent For First-Line Treatment Of Frail And/ Or Unfit For Polychemotherapy (Pcht) Patients (Pts) With Metastatic Colorectal Cancer (Mcrc): A Phase Ii Study Of The Spanish Cooperative Group For Digestive Tumor Therapy (Ttd).

3527 Background: A 15-20% of pts diagnosed of mCRC do not qualify to receive PChT as first-line therapy, due to age and/or comorbidities, and their optimal treatment strategy has not been defined. REG is an oral multikinase inhibitor indicated for pretreated mCRC. We aimed to assess the efficacy and safety of REG as a single agent in first-line setting of this frail and/or unfit patient population. Methods: Phase II, single-arm study in frail and/or unfit to receive PChT, mCRC pts. Inclusion criteria: pts ≥ 18 years, ECOG PS ≤ 2, adequate organ function, at least one of the following: dependence in activities of daily living, presence of 3 or more comorbidities or geriatric syndromes. Primary endpoint was progression-free survival (PFS) rate at 6 months. Pts received REG 160 mg PO, 3 weeks on/1 week off, in a 4-week cycle. Results: Forty-seven pts were included. Median age was 80 years (range 63-89), 36% had ECOG 2, 55% were dependent, 38% had geriatric syndromes and 57% ≥ 3 comorbidities; 63.8% had ≥ 2-affected organs and 34% did not undergo primary tumor surgery. Treatment: 192 cycles were administered (median 2, range 1-16). Median dose intensity was 75% due to dose reductions (DR) or delays. Average daily dose: 90.4 mg/day. Response rate 6.4%, disease control rate 51.1%. Median PFS 5 months. Six-month PFS rate: 43.6%. Median overall survival, 16.7 months. Eleven (23.4%) pts discontinued treatment due to toxicity. Three pts (6.4%) had grade 4 toxicity: hypertension, hyperuricemia and lipase increase, and two pts grade 5 toxicity: one sudden death and one rectorrhagia. Most frequent grade 3-4 toxicities: hypertension (37.5%), fatigue (35.0%), hypophosphatemia (15.0%) and increased AST (7.5%). Grade 2-3 skin toxicity, 19.1% of pts. Conclusions: In this group of mCRC pts, REG at a standard starting dose showed a modest antitumor activity and led to a considerable rate of adverse events with frequent DR and/or delays. In the absence of reliable biomarkers, first-line full-dose REG in frail and/or unfit mCRC pts did not achieve the prespecified efficacy threshold (55% PFS rate at 6 months). Clinical trial information: NCT01875380.