Phase II study of biweekly TAS-102, irinotecan and bevacizumab in pre-treated metastatic colorectal cancer (TABAsCO).

Authors

null

Patrick M Boland

Rutgers Cancer Institute of New Jersey, New Brunswick, NJ

Patrick M Boland , Sarbajit Mukherjee , Iman Imanirad , Namrata Vijayvergia , Seth D. Cohen , Medhavi Gupta , Renuka V. Iyer , Sarah Chatley , Beth Cahill , Deepak Vadehra , Kristopher Attwood , Howard S. Hochster , Christos Fountzilas

Organizations

Rutgers Cancer Institute of New Jersey, New Brunswick, NJ, Roswell Park Comprehensive Cancer Center, Buffalo, NY, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, Fox Chase Cancer Center, Philadelphia, PA, RWJBarnabas Health, Monmouth, NJ, Brown University Women and Infants Hospital, Providence, RI, Rutgers Cancer Institue of New Jersey, New Brunswick, NJ

Research Funding

Other
NCCN Oncology Research Program

Background: The efficacy of 2nd line FOLFIRI plus VEGF inhibition (VEGFi) is limited for metastatic colorectal cancer (mCRC). TAS-102 is a novel oral anti-metabolite approved for pts with mCRC following standard treatment with FP, oxaliplatin and irinotecan. TAS-102 has a distinct mechanism of action from 5-FU and overcomes 5-FU resistance in preclinical models, and in the clinic. We hypothesized that the combination of TAS-102 with irinotecan (TAS-IRI) and bevacizumab (BEV) would prove superior to FOLFIRI/VEGFi. Methods: Phase II, single-arm study of TAS-IRI and BEV in 2nd-line mCRC. Eligible patients had received prior treatment with a fluoropyrimidine and oxaliplatin in the advanced setting or experienced recurrence within 12 mos of this regimen in the adjuvant setting. Adequate organ function, ECOG PS 0-1, measurable disease (RECIST 1.1), no prior irinotecan or TAS-102 exposure and candidacy for BEV were required. Pts were treated with BEV 5 mg/kg IV, irinotecan 180 mg/m2 IV (day 1 and 15), and TAS-102 25 mg/m2 orally bid (days 2-6 and 16-20) in 4-week cycles (PMID: 31924737). Treatment continued until disease progression or unacceptable toxicity. The primary endpoint was median progression-free survival (PFS). Assuming a median PFS for historic control (FOLFIRI/VEGFi) of 6 mos vs. 9 mos for TAS-IRI plus BEV (HR: 0.67), treatment of 36 evaluable pts would achieve 80.5% power (at α = 0.1) to detect such an effect. Results: Forty-nine patients were enrolled; 42 were eligible and 38 had at least one disease assessment (median age 59 yr, 47% male, 74% colon primary, tumor KRAS/NRAS mutated in 55%/21%). The median PFS was 8.7 mos (range: 6.7-11.8 mos, p = 0.009), meeting the primary endpoint. The most common reason for study treatment discontinuation was progressive disease (53%). The objective response rate was 16% (90% CI: 8.0-27.3%); the median OS was 16.5 mo (range: 11.8-25.3). Twenty-eight pts (67%) had a treatment-related adverse event (TRAE) G3 or higher (Table). The most common TRAEs were gastrointestinal and hematologic. Grade 3/4 neutropenia occurred in 34%, with only 1 episode of febile neutropenia, though G-CSF use was frequently needed to maintain dose density/intensity. Conclusions: TAS-IRI plus BEV is an effective 2nd line therapy for patients with mCRC. The median PFS appears higher compared to historical controls (FOLFIRI/VEGFi). Neutropenia is common and can affect dose density/intensity mandating use of G-CSF. A randomized study versus standard of care therapy is warranted. (Clinical trial registration ClinicalTrials.gov NCT04109924). Clinical trial information: NCT04109924.

TRAETotal (%)Grade 3/4(%)
Neutropenia27 (71)13 (34)
Diarrhea25 (66)6 (16)
Nausea25 (66)-
Fatigue22 (58)1 (3)
Alopecia14 (37)-
Anemia12 (32)5 (13)
Anorexia12 (32)1 (3)
Vomiting11 (29)-
Thrombocytopenia9 (24)2 (5)
Constipation7 (18)-
Epistaxis7 (18)-
Infusion related reaction6 (16)-
Abdominal pain5 (13)3 (8)

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Abstract Details

Meeting

2023 ASCO Annual Meeting

Session Type

Poster Session

Session Title

Gastrointestinal Cancer—Colorectal and Anal

Track

Gastrointestinal Cancer—Colorectal and Anal

Sub Track

Colorectal Cancer–Advanced Disease

Clinical Trial Registration Number

NCT04109924

Citation

J Clin Oncol 41, 2023 (suppl 16; abstr 3590)

DOI

10.1200/JCO.2023.41.16_suppl.3590

Abstract #

3590

Poster Bd #

290

Abstract Disclosures