1088 - Phase II trial to evaluate efficacy and tolerance of regorafenib monotherapy in patients (pts) over 70 with previously treated metastatic colorectal adenocarcinoma (mCRC) FFCD 1404 - REGOLD

Background

Regorafenib (REG) significantly increases overall survival (OS) in previously treated mCRC pts. However, no prospective trial specific to elderly population including geriatric parameter evaluation has evaluated the safety and efficacy of REG in its registered indication.

Methods

Multicenter one-arm phase II that enrolled pts ≥70 years, ECOG performance status ≤1, with mCRC after failure of fluoropyrimidine-based chemotherapy, anti-VEGF and anti-EGFR treatment. Primary endpoint was tumor control rate 2 months after initiation of REG administered at 160mg/day (3weeks on/1 week off).

Results

43 pts were enrolled from January 2016 to April 2017, median age 77 (range 70 – 91), ECOG 0: 37.2%, ECOG 1: 60.5%, altered activities of daily living (ADL) in 37.5%. Median time from diagnosis of metastases to enrolment: 27.7 months, median number of previous lines: 3. At the time of analysis, the median follow-up was 13.3 months and 62.8% pts had died. One patient never started treatment. The median duration of REG treatment was 45.0 days [5 to 440]. 8 patients were not evaluable for the primary endpoint. Tumor control rate at 2 months in the 35 evaluable pts was 31.4% [18.7% – 46.6%]. Among the 11 pts with tumor control, 9 (81.8%) were < 80 yrs. In the 42 treated pts, median progression free survival (PFS) and OS were 2.2 [1.9-3.3] and 7.5 [5.5-14.6] months, respectively. Modification of the initial dose was performed in 54.3% of the 116 cycles delivered. A grade 3-4 adverse event was observed in 37 (88.1%) pts notably: asthenia (45.2%), hand foot syndrome (21.4%), arterial hypertension (21.4%), and diarrhea (7.1%). Treatment was stopped for toxicity without progression in 12 (28.6%) pts. Among them, 10 (83.3%) pts were ECOG 1, 6 (50%) were over 80 years and 6 (50%) had abnormal baseline ADL. No toxic death was observed.

Conclusions

Treatment with REG in heavily pretreated elderly pts gives a tumor control at 2 months in around 30% of pts. The median PFS and OS are comparable to those observed in the pivotal study. With caution due to small number, drop-out rate for treatment toxicity seems higher in pts with ECOG 1, age over 80 yrs and abnormal ADL.

Clinical trial identification

EudraCT: 2015-002086-29.

Legal entity responsible for the study

Fédération Francophone de Cancérologie Digestive.

Funding

Bayer.

Editorial Acknowledgement

Disclosure

T. Aparicio: Consulting or advisory role: Pierre Fabre, Ipsen, Halio DX, Bristol-Myers Squibb; Travel, accommodations, expenses: Ipsen, Novartis, Ipsen, Roche, Hospira; Honoraria: Pfizer, Roche, Sanofi, Léo Pharma, Amgen, Bristol-Myers Squibb, Servier; Research funding: Bayer. A. Darut Jouve: Travel, accommodations, expenses: Novartis, Bayer. F. Khemissa: Travel, accommodations, expenses: Ipsen, Roche, Sanofi, Bayer; Honoraria: Sanofi, Roche, Bayer; Speakers' bureau: Sanofi, Roche. P. Artru: Consulting or advisory role: Roche, Merck; Travel, accommodations, expenses: Roche, Merck, Bayer; Honoraria: Roche, Amgen, Bayer, Servier, Lilly, Merck; Speakers' bureau: Roche, Merck, Servier. L. Cany: Travel, accommodations, expenses: Novartis. O. Romano: Consulting or advisory role: Roche, Sanofi, Pierre Fabre; Travel, accommodations, expenses: Novartis; Honoraria: Roche, Sanofi, Pierre Fabre; Research funding: Sanofi. C. Falandry: Consulting or advisory role: Pfizer, AstraZeneca, Novartis, Teva, Pierre Fabre, Roche; travel, accommodations, expenses: AstraZeneca, Roche, Pfizer; Honoraria: Pfizer, AstraZeneca, Novartis. M. Duluc: ravel, accommodations, expenses: Ipsen. J.L. Legoux: Consulting or advisory role: Lilly, Novartis; Travel, accommodations, expenses: Merck Serono, Lilly, Ipsen, Novartis; Honoraria: Novartis Research funding: Sanofi/Regeneron. M. Ben Abdelghani: Consulting or advisory role: Amgen, Sanofi, Merck Serono, Bayer, Ipsen, Novartis/Pfizer Travel, accommodations, expenses: Roche, Amgen, Novartis/Pfizer, Ipsen, Bayer, Sandoz, Sanofi. E. Assenat: Consulting or advisory role: Ipsen, Sanofi; Travel, accommodations, expenses: Bayer, Ipsen; Honoraria: Bayer, Sirtex Medical. M. Dhooge: Travel, accommodations, expenses: Norgine SAS. C. Lepage: Consulting or advisory role: Advanced Accelerator Applications; Travel, accommodations, expenses: Amgen, Novartis, Ipsen, Bayer; Honoraria: Novartis. All other authors have declared no conflicts of interest.