medwireNews: End-of-study findings from the GIM2 trial indicate that adjuvant anthracyclines plus taxane chemotherapy for high-risk early breast cancer should be given in a dose-dense regimen and should not include fluorouracil.
The results are published in The Lancet Oncology following an earlier presentation at the ESMO Congress 2022 in Paris, France, by lead investigator Lucia Del Mastro (IRCCS Ospedale Policlinico San Martino, Genova, Italy).
“Although these results are from an old study, which was not planned according to the modern concept of different breast cancer subtypes, these findings are still useful for optimising adjuvant chemotherapy regimen in patients with breast cancer at high risk of relapse,” the authors say.
They explain that the GIM2 study previously demonstrated that women with node-positive early breast cancer did not derive a significant survival benefit from the use of fluorouracil alongside epirubicin, cyclophosphamide, and paclitaxel, but that giving the regimen every 2 weeks instead of every 3 weeks improved both disease-free survival (DFS) and overall survival (OS).
The current analysis, after a median follow-up of 15.1 years, confirmed that there was no significant difference in DFS between the 1044 patients who were and the 1047 patients who were not given fluorouracil (median 17.09 years vs not reached).
And the 1002 patients given the dose-dense 2-week schedule, when compared with the 1001 patients given the standard 3-week regimen, experienced significantly longer median DFS (not reached vs 16.52 years; hazard ratio [HR]=0.77) and median OS (unreached vs unreached; HR=0.72).
Post-hoc analysis did not show an interaction between hormone receptor status and the outcome of a 2-week versus 3-week chemotherapy schedule or by use of fluorouracil.
The most commonly reported grade 3–4 adverse event was neutropenia, affecting 48% and 37% of patients given dose-dense regimens who did and did not receive fluorouracil, respectively, and 20% and 10% of those given standard-dose regimens with and without fluorouracil, respectively. The corresponding rates of alopecia were 47%, 44%, 46%, and 48%.
There were no treatment-related deaths in the study, and during the extended follow-up there were no further grade 3 or 4 adverse events, the researchers say.
The authors of a linked comment say that in the “modern era driven by treatment tailoring, results of a study aged 20 years recommending chemotherapy escalation for all subtypes indiscriminately might feel anachronistic.”
But Stefania Morganti and Sara Tolaney, both from the Dana-Farber Cancer Institute in Boston, Massachusetts, USA, believe the findings can be “contextualised in current practice.”
They acknowledge that dose-intensification did not show benefits for women with HER2-positive tumors in GIM2 and its use “remains unclear” in this population, whereas dose-dense chemotherapy is “already well established” for triple-negative breast cancer and the debate now focuses on the use of pembrolizumab.
Moreover, the commentators say that the use of dose-dense chemotherapy is “more controversial” for patients with estrogen receptor (ER)-positive or HER2-negative disease, following results from the RxPONDER and MINDACT studies indicating that the “intrinsic biology” of ER-positive tumors “makes them insensitive to cytotoxic agents.”
Nevertheless, Morganti and Tolaney believe that the GIM2 study “supports a preference for dose-intensification when an anthracycline-based regimen is chosen, but keeping in mind that anthracyclines can be safely spared in many patients with [ER]-positive disease.”
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Lancet Oncol 2022; doi: 10.1016/ S1470-2045(22)00632-5
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