Abstract 2383
Background
In the phase 3 randomized CORRECT trial, REG improved survival vs placebo in treatment-refractory mCRC; 19% of REG-treated patients had PFS >4 m. In the single-arm phase 3b CONSIGN trial (NCT01538680) of REG, adverse events (AEs) and PFS were consistent with phase 3 trials in mCRC. We performed a retrospective analysis of CONSIGN patients with PFS >4 m (long PFS) and ≤4 m (short PFS).
Methods
Patients with treatment-refractory mCRC received REG 160 mg QD for 3 wks on/1 wk off until disease progression, death, or unacceptable toxicity. Treatment beyond progression was at the investigator's discretion. PFS (investigator assessed) was the time from treatment assignment to progression or death. Of 2872 patients assigned to REG, 674 (23%) had long PFS and 2198 (77%) had short PFS. Descriptive statistics are reported.
Results
Compared to the short PFS group, the long PFS group had a higher proportion of patients with ECOG PS 0, with no liver metastases, and ≥18 m since diagnosis of metastatic disease (Table). Long PFS patients received a median of 7 cycles (2–29); 75% ≥6 cycles; 34% ≥9 cycles. Short PFS patients received a median of 2 cycles (1–33). Dose reductions due to AEs (long PFS, short PFS) were 65%, 40%; actual mean daily doses were 136 mg, 149 mg, respectively. The most common drug-related NCI-CTCAE v4 grade ≥3 AEs (long PFS, short PFS) were hypertension (20%, 14%), hand–foot skin reaction (19%, 12%), fatigue (13%, 13%), diarrhea (8%, 4%), and hypophosphatemia (8%, 4%).
Long PFS (n = 674) | Short PFS (n = 2198) | |
---|---|---|
Median age, yrs (range) | 62 (27–86) | 62 (19–89) |
Age, % ≥70 yrs ≥75 yrs | 19 8 | 23 10 |
ECOG PS, % 0 1 | 58 41 | 44 56 |
Liver metastases, % No Yes | 32 67 | 20 80 |
KRAS status, % mutant wild-type | 47 49 | 52 43 |
Primary site of disease, % Colon Rectum Both | 66 28 6 | 64 28 8 |
No. of prior regimens on or after diagnosis of metastatic disease, % 0–2 3 ≥4 | 22 28 50 | 28 27 45 |
Time since first diagnosis of metastatic disease to treatment assignment, % ConclusionsThis exploratory analysis suggests that among patients with mCRC treated with regorafenib, the long PFS (>4 months) subgroup tended to have a higher proportion of patients with better performance status, with no liver involvement, and a longer time since diagnosis of metastatic disease. Higher rates of some AEs and dose reductions in the long PFS group may be related to longer treatment duration. Clinical trial identificationNCT01538680 Legal entity responsible for the studyBayer FundingBayer DisclosureR. Garcia-Carbonero: Advisory board: Roche, Amgen, Merck, Sanofi, Lilly, Boehringer Ingelheim, Bayer, Novartis, Ipsen. E. Van Cutsem: Corporate-sponsored research: Bayer. F. Ciardiello: Advisory board: Bayer, Roche, Merck Serono, Lilly, Sanofi, AstraZeneca. Corporate-sponsored research: AstraZeneca, Merck Serono, Roche, Bayer. M. Ychou: Advisory board: Bayer, Roche, Merck. J-F. Seitz: Advisory board: Roche, Sanofi-Aventis. R.D. Hofheinz: Corporate-sponsored research: Amgen, Medac, Merck, Roche, Sanofi. U. Verma: Advisory board: Bayer. Speakers bureau: Intramed. A. Grothey: Advisory board: Bayer Corporate-sponsored research: Bayer (institute). A. Miriyala, J. Kalmus, C. Kappeler: Stock ownership: Bayer. Other substantive relationships: Bayer (employee). A. Falcone: Advisory board: Amgen, Roche, Bayer, Lilly, Sanofi, Servier, Merck. Corporate-sponsored research: Roche, Amgen, Bayer, Merck, Sanofi. All other authors have declared no conflicts of interest. Resources from the same session2354 - The clinicopathologic features and treatment of 607 hindgut neuroendocrine tumor (NET) patients at a single institutionPresenter: Seung Tae Kim Session: Poster Display Resources: Abstract 2594 - Neuroendocrine carcinomas of the colorectal origin - Polish experiencePresenter: Agnieszka Kolasińska-Ćwikła Session: Poster Display Resources: Abstract 2539 - Neuroendocrine neoplasms of the appendix including goblet cell carcinoidsPresenter: Agnieszka Kolasinska-Cwikla Session: Poster Display Resources: Abstract 1245 - Prognostic validity of AJCC staging system in neuroendocrine tumors of the appendixPresenter: Amir Mehrvarz Sarshekeh Session: Poster Display Resources: Abstract 3902 - Enhancer of zest homolog 2 (EZH2) expression in well and moderately differentiated pancreatic neuroendocrine tumor (pNET)Presenter: Riccardo Marconcini Session: Poster Display Resources: Abstract 3882 - Differential clinical and pathological characteristics of hereditary neuroendocrine pancreatic tumours (NEPT)Presenter: Gema Marín Zafra Session: Poster Display Resources: Abstract 2296 - Natural course of thyroid cancer nodules compared with benign thyroid nodulesPresenter: Kyung-Jin Yun Session: Poster Display Resources: Abstract 4083 - Reassessment of proliferative activity at disease progression in neuroendocrine neoplasmsPresenter: Noemi Cicchese Session: Poster Display Resources: Abstract 3866 - 18F-FDG-PET to predict disease progression in advanced digestive neuroendocrine neoplasmsPresenter: Maria Rinzivillo Session: Poster Display Resources: Abstract 3651 - UK phase IV, observational study to assess quality of life in patients (pts) with pancreatic neuroendocrine tumours (pNETS) receiving treatment with everolimus: The “real-world” OBLIQUE studyPresenter: John Ramage Session: Poster Display Resources: Abstract This site uses cookies. Some of these cookies are essential, while others help us improve your experience by providing insights into how the site is being used. For more detailed information on the cookies we use, please check our Privacy Policy.
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