Author: By Lynda Williams, Senior medwireNews Reporter
medwireNews: PATTERN trial results indicate that adjuvant paclitaxel plus carboplatin might offer an alternative to a conventional anthracycline-based regimen for triple-negative breast cancer (TNBC) patients with node-positive disease or node-negative disease but a tumour of more than 10 mm in diameter.
“The value of platinum-based adjuvant chemotherapy in patients with [TNBC] remains controversial, as does whether BRCA1 and BRCA2 (BRCA1/2) germline variants are associated with platinum treatment sensitivity”, explain Zhi-Ming Shao, from Fudan University in Shanghai, China, and co-workers in JAMA Oncology.
To investigate further, the team designed a phase III trial comparing six cycles of paclitaxel 80 mg/m2 plus carboplatin AUC2 on days 1, 8 and 15 every 28 days versus three 21-day cycles of cyclophosphamide 500 mg/m2, epirubicin 100 mg/m2 and fluorouracil 500 mg/m2, followed by three cycles of docetaxel 100 mg/m2 every 21 days (CEF-T).
After a median 62 months of follow-up, the primary endpoint of 5-year disease-free survival (DFS) was significantly higher for the 325 patients assigned to receive paclitaxel plus carboplatin after surgery than the 322 participants who instead received CEF-T, at 86.5% versus 80.3% and a hazard ratio (HR) of 0.65.
Paclitaxel plus carboplatin also achieved a significantly higher 5-year rate of recurrence-free survival (91.2 vs 84.4%, HR=0.54), as well as a positive trend towards better 5-year distant DFS (92.6 vs 87.9%, HR=0.59).
And overall survival at 5 years was comparable between the treatment arms, at 93.4% for paclitaxel plus carboplatin versus 89.8% for CEF-T.
However, the researchers emphasize the need for “long-term follow-up and more events” for this endpoint, noting that their survival results “should be considered with caution, as high-level evidence is still lacking to make platinum-based chemotherapy the new standard of care.”
Acknowledging that “identifying predictive biomarkers is imperative for the selection of appropriate patients for platinum-based regimens in the adjuvant setting”, the team performed several “hypothesis-generating subgroup analyses”.
The researchers found that paclitaxel plus carboplatin might have had greater DFS benefit over CEF-T for the 66 patients with a confirmed germline BRCA1/2 mutation compared with the 472 patients without BRCA1/2 mutations, with HRs of 0.44 and 0.68, respectively, although they admit that the interaction P value of 0.37 suggests that “this difference could be attributed to chance given the small number of participants with BRCA variants.”
Moreover, patients with germline variants in one of 12 homologous recombination repair genes, including BRCA1/2, might benefit more from paclitaxel plus cisplatin than CEF-T, with DFS rates of 88.4% versus 76.3% and a HR of 0.39, they say.
Zhi-Ming Shao et al add that both the paclitaxel plus carboplatin and CEF-T regimens were “generally well tolerated, and treatment-related deaths or life-threatening events were not observed.”
The majority of adverse events were haematological; patients in the paclitaxel plus carboplatin arm were more likely to experience anaemia, thrombocytopenia or peripheral neuropathy than those in the CEF-T arm but less likely to have febrile neutropenia.
Reference
Yu K-D, Ye F-G, He M, et al. Effect of adjuvant paclitaxel and carboplatin on survival in women with triple-negative breast cancer. A phase 3 randomized clinical trial. JAMA Oncol; Advance online publication 13 August 2020. doi:10.1001/jamaoncol.2020.2965
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