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TAS-102 Plus Bevacizumab May Be ‘New Treatment Option’ For Chemorefractory Metastatic CRC

Phase II trial investigators report improved progression-free survival with use of trifluridine–tipiracil alongside bevacizumab in metastatic colorectal cancer patients unable to undergo further chemotherapy
31 Jan 2020
Anticancer Agents;  Colon and Rectal Cancer

Author: By Lynda Williams, Senior medwireNews Reporter

medwireNews: The addition of bevacizumab to TAS-102 significantly extends progression-free survival (PFS) for metastatic colorectal cancer (mCRC) patients unable to undergo conventional chemotherapy, suggest results from an open-label trial. 

The investigator-initiated phase II study included 93 heavily pretreated patients attending four Danish centres who were intolerant or refractory to fluoropyrimidine, irinotecan, oxaliplatin or, for RAS wild-type patients, cetuximab or panitumumab.  

A median PFS of 4.6 months was achieved by the 46 participants who were randomly assigned to receive oral TAS-102 – also known as trifluridine–tipiracil – at a dose of 35 mg/m2 twice daily on days 1–5 and 8–12 of each 28-day cycle, alongside bevacizumab 5 mg/kg on days 1 and 15. 

This was significantly better than the PFS of 2.6 months reported for the 47 patients who received only TAS-102, giving a hazard ratio of 0.45 for disease progression or death in favour of the combination. 

At data cutoff, after a median of 10.0 months of follow-up, 60% of the patients had died, with median overall survival of 9.4 months with the combination regimen versus 6.7 months with TAS-102 alone, giving a significant HR of 0.55. 

One patient given TAS-102 plus bevacizumab achieved a partial response and disease control was achieved by 67% of the combination group versus 51% of those in the TAS-102 arm. 

Neutropenia was the most common grade 3 or worse adverse event, affecting 67% of patients given TAS-102 plus bevacizumab versus 38% of patients given TAS-102 monotherapy. Severe events included febrile neutropenia in three patients given the combination regimen and one patient given TAS-102 alone.

“The combination of TAS-102 plus bevacizumab is an encouraging new potential treatment option in patients with refractory metastatic colorectal cancer and could be practice changing”, say Per Pfeiffer, from Odense University Hospital in Denmark, and co-workers. 

Discussing the study findings in a linked comment, Cathy Eng, from Vanderbilt-Ingram Cancer Center in Nashville, Tennessee, USA, writes that “[c]learly this trial was an unmet need for the Danish patient population given the rapid enrollment of 93 patients over the 9-month period from a small number of participating institutions.”

Nevertheless, the commentator notes that over 40% of patients in each treatment arm were admitted to hospital at least once; this may be linked to the high incidence of neutropenia, the cause of which “remains unclear given the small number of neutropenia cases with single agent bevacizumab.”

Cathy Eng continues: “Given that the average age a patient is diagnosed with colorectal cancer is 67 years, similar to the median age of patients in both groups from this trial, it is likely we will see greater incidences of neutropenia in a real-world setting, potentially placing patients at increased risk of morbidity and mortality.”

She therefore suggests that alternative TAS-102 schedules and use of granulocyte colony-stimulating factor may be required to combat neutropenia with the combination regimen.

“Although this trial provides promising results for TAS-102 with bevacizumab, additional data are warranted before treatment guidelines are changed”, she concludes.


Pfeiffer P, Yilmaz M, Möller S, et al. TAS-102 with or without bevacizumab in patients with chemorefractory metastatic colorectal cancer: an investigator-initiated, open-label, randomised, phase 2 trial. Lancet Oncol; Advance online publication 27 January 2020. https://doi.org/10.1016/S1470-2045(19)30827-7 

Eng C. TAS-102 plus bevacizumab: a new standard for metastatic colorectal cancer? Lancet Oncol; Advance online publication 27 January 2020. https://doi.org/10.1016/S1470-2045(20)30009-7

medwireNews (www.medwireNews.com ) is an independent medical news service provided by Springer Healthcare. © 2020 Springer Healthcare part of the Springer Nature group

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