tAnGo At 10 Years Shows Adding Gemcitabine Does Not Boost Early Breast Cancer Survival

Final results from the tAnGo study of women with early breast cancer rule out the use of gemcitabine with adjuvant anthracycline and taxol chemotherapy

medwireNews: Ten-year results from tAnGo confirm that adding gemcitabine to an adjuvant regimen of epirubicin, cyclophosphamide and paclitaxel does not improve disease-free survival (DFS) or overall survival (OS) in any subgroup of patients with a new diagnosis of early breast cancer.

The final findings, published in The Lancet Oncology, also show increased toxicity with gemcitabine use compared with the standard regimen, including higher rates of myelosuppression, fatigue and infection.

When viewed alongside those of the NSABP B-38 trial, the tAnGo results “leave no doubt that gemcitabine has no proven role in the adjuvant setting”, writes the author of a linked comment, Dimitrios Mavroudis, from University Hospital of Heraklion in Crete, Greece.

“Unfortunately, the same is true for gemcitabine in the neoadjuvant setting, based on results of the companion study Neo-tAnGo and the NSABP B-40 trial”, he adds.

The protocol-specified final analysis, after a median of 10 years’ follow-up, includes data for 1087 DFS events and 914 deaths among the 1570 patients given open-label epirubicin, cyclophosphamide and paclitaxel plus gemcitabine and the 1571 patients given chemotherapy without gemcitabine.

DFS rates were comparable between the groups at 2, 5 and 10 years; 10-year DFS was achieved by 65% of patients in both treatment arms and median DFS was not reached.

Rates of OS were similar at 2, 5 and 10 years for the gemcitabine and control groups, with 70% and 71% alive at the 10-year mark, respectively. And breast cancer-specific survival was also comparable, with 25% and 26% of patients in each group, respectively, dying from breast cancer.

Furthermore, forest plot analyses failed to identify a significant DFS treatment benefit with gemcitabine for any subgroups of patients based on tumour nodal status, hormone or genetic biomarkers, or patient age and performance status.

Adverse events records for 1565 gemcitabine-treated patients and 1567 controls initially suggested that the regimens were “similarly well tolerated”, observe Helena Earl, from the University of Cambridge in the UK, and co-investigators.

However, the final analysis revealed that gemcitabine use was associated with a higher rate of grade 3 adverse events, including neutropenia, myalgia and arthralgia, fatigue, infection, vomiting and nausea, neurosensory neuropathy, fever, diarrhoea and constipation, and anaemia and thrombocytopenia.

“It is difficult to explain why the overall results for adjuvant gemcitabine were negative when the drug had seemed so promising in the metastatic setting, especially given the ongoing positive results in metastatic triple-negative breast cancer”, the researchers say.

Nevertheless, Helena Earl et al emphasize that “[t]he rejection of gemcitabine from standard adjuvant breast cancer treatment because of an absence of benefit can be seen as a cost-effective result in terms of both financial and patient toxicity costs.”

They add that “[F]urther improvements in treatment outcomes for women with early breast cancer are likely to depend on the development of targeted therapies whose selective application is predicated on the biological heterogeneity of this disease.”

References

Earl HM, Hiller L, Howard HC, et al. Addition of gemcitabine to paclitaxel, epirubicin, and cyclophosphamide adjuvant chemotherapy for women with early-stage breast cancer (tAnGo): final 10-year follow-up of an open-label, randomised, phase 3 trial. Lancet Oncol; Advance online publication 4 May 2017. DOI: http://dx.doi.org/10.1016/S1470-2045(17)30319-4

Mavroudis D. The tAnGo fell short of inspiring the audience. Lancet Oncol; Advance online publication 4 May 2017. DOI: http://dx.doi.org/10.1016/S1470-2045(17)30311-X

medwireNews is an independent medical news service provided by Springer Healthcare. © 2017 Springer Healthcare part of the Springer Nature group