In CORRECT, REG significantly improved overall survival and PFS vs placebo in pts with treatment-refractory mCRC. We did a retrospective, exploratory subgroup analysis of REG-treated pts in CORRECT with PFS >4 m (long PFS) and ≤4 m (short PFS).
Pts with pretreated mCRC were randomized 2:1 to REG 160 mg or placebo QD for 3 weeks on/1 week off until disease progression, death, or unacceptable toxicity. PFS was the time from randomization to progression or death. Of 505 pts randomized to REG, 98 (19%) had long PFS and 407 (81%) had short PFS.
Compared to short PFS pts, the long PFS group had a higher proportion of patients with ECOG PS0, 1–2 tumor sites, and ≥18 m since diagnosis of metastatic disease (Table). Long PFS pts received a median of 6 (1–12) cycles, short PFS pts a median of 2 (1–11). Mean actual daily doses were 138.7 mg (long PFS) and 149.2 mg (short PFS). Dose modifications occurred in 91% (long PFS) and 72% (short PFS). NCI-CTCAE (v3) grade (Gr) ≥3 REG-related treatment-emergent adverse events (TEAE) occurred in 64% (long PFS) and 53% (short PFS). Most common REG-related Gr ≥3 TEAEs included (long PFS, short PFS) hand–foot skin reaction (20%, 16%), hypertension (17%, 5%), fatigue (13%, 9%), diarrhea (16%, 5%), rash/desquamation (3%, 6%), and hypophosphatemia (5%, 3%). Gr ≥3 laboratory toxicities (long PFS, short PFS) included increased bilirubin (8%, 13%), ALT (6%, 5%), and AST (5%, 6%). Although REG-related TEAEs led to a higher dose modification rate in long PFS pts (71% vs 52% for short PFS), discontinuations due to REG-related TEAEs were similar (long PFS 5%; short PFS 9%).
|Long PFS (n = 98)||Short PFS (n = 407)|
|Median age, yrs (range)||61 (34–82)||61 (22–82)|
|Median body mass index, kg/m2||25.6||24.7|
|ECOG PS, % 0 1||63 37||50 50|
|No. of tumor sites, % 1 2 3 ≥4||30 38 16 16||17 35 30 18|
|KRAS status, % mutant wildtype||47 44||56 40|
|Primary site of disease, % Colon Rectum Both||52 37 10||67 28 5|
|No. of prior regimens on or after diagnosis of metastatic disease, % 0–2 3 ≥4||22 22 55||28 25 47|
|Time since first diagnosis of metastatic disease to randomization, % |
This exploratory analysis showed that pts with mCRC treated with REG who had PFS >4 m tended to have a better performance status, fewer metastatic tumor sites, and a longer time since diagnosis of metastatic disease, compared to pts with short PFS.
Clinical trial identification
Legal entity responsible for the study
A. Grothey: Advisory board: Bayer. Corporate-sponsored research: Bayer. A. Falcone: Advisory board: Amgen, Roche, Bayer, Lilly, Sanofi, Servier, Merck. Corporate-sponsored research: Roche, Amgen, Bayer, Merck, Sanofi. O. Bouche: Advisory board: Merck Serono, Roche. L. Mineur: Advisory board participation. A. Adenis: Corporate-sponsored research: Bayer, Sanofi Other substantive relationship: Bayer, Sanofi, Pfizer, Roche. J. Tabernero: Advisory board: Amgen, Bayer, Boehringer Ingelheim, Celgene, Chugai, Lilly, MSD, Merck Serono, Novartis, Roche, Sanofi, Symphogen, Takeda, Taiho. T. Yoshino: Corporate-sponsored research: GlaxoSmithKline K.K. Boehringer Ingelheim GmbH H-J. Lenz: Advisory board: Bayer. Lectures: Bayer. Clinical trial support: Bayer. R.M. Goldberg: Corporate-sponsored research: Bayer. L. Huang: Stock ownership: Bayer Other substantive relationships: Bayer (employee). A. Wagner: Other substantive relationships: Bayer (employee). E. Van Cutsem: Corporate-sponsored research: Bayer. All other authors have declared no conflicts of interest.