Paclitaxel-carboplatin an adjuvant chemo alternative for women with operable TNBC

A paclitaxel-carboplatin (PCb) regimen may be an alternative adjuvant chemotherapeutic strategy for women with operable triple-negative breast cancer (TNBC), given its greater benefit over a conventional regimen comprising cyclophosphamide, epirubicin, and fluorouracil, followed by docetaxel (CEF-T), the phase III PATTERN* trial has shown.

Compared with other BC subtypes, TNBC is more likely to have a higher histologic grade and be more aggressive, thus increasing the risk of local recurrence and visceral metastasis. [N Engl J Med 2010;363:1938-1948] “[P]latinum-containing regimens have been proven to be effective in gBRCA1/2 variant carriers [in the neoadjuvant setting],” said the researchers. However, there is insufficient evidence for platinum-based therapy in the adjuvant setting, they pointed out.

“[As such, we sought] to determine whether PCb is superior to CEF-T in the adjuvant setting of TNBC … [F]or the first time, to our knowledge, [our findings showed that the platinum-based regimen] is superior to the anthracycline/taxane regimen for early-stage TNBC,” they said.

A total of 647 women (mean age 51 years) with early-stage TNBC (74 percent node-negative) were randomized to receive either PCb** or CEF-T***. CT completion rates were high in both PCb and CEF-T arms (95 percent and 93 percent, respectively). About 9 percent required dose reductions. [JAMA Oncol 2020;doi:10.1001/jamaoncol.2020.2965]

At a median follow-up of 62 months, there were fewer disease-free survival (DFS) events with PCb vs CEF-T (n=42 vs 62), translating to a significantly higher 5-year DFS rate with the former vs the latter regimen (86 percent vs 80 percent; hazard ratio [HR], 0.65; p=0.03).

PCb also outdid CEF-T in terms of distant DFS (n=22 vs 36 events; 93 percent vs 88 percent; HR, 0.59; p=0.05) and relapse-free survival (n=26 vs 46 events; 91 percent vs 84 percent; HR, 0.54; p=0.01).

Overall survival (OS) rates were similar between PCb and CEF-T (93 percent vs 90 percent; HR, 0.71; p=0.22). “[A]dequate efficacy assessment of PCb on OS will require long-term follow-up and more events,” said the researchers.

Both regimens were well-tolerated, with no fatal events or treatment-related deaths reported. Haematologic toxicity was predominant, the most common being anaemia and thrombocytopenia for PCb, and grade 3/4 febrile neutropenia for CEF-T.

However, the findings should be interpreted with caution, as evidence supporting the potential of platinum-based chemotherapy as a new standard of care in this setting is lacking, noted the researchers. Confirmatory trials for ethnic extrapolation are also warranted as the current study only evaluated Chinese patients, they added.

It is also important to note that CEF-T is no longer a primary recommendation in the NCCN^# guidelines. Updated ECOG^## data identified epirubicin and cyclophosphamide followed by weekly paclitaxel (EC-wP) as a potential regimen for TNBC. [N Engl J Med 2008;358:1663-1671] “However, we lack a head-to-head comparison between CEF-T and EC-wP, and … our trial predominantly enrolled patients with early-stage TNBC. In such patients with a lower tumour burden, whether an EC-wP regimen is the optimal choice remains inconclusive.”

Future trials should also explore predictive biomarkers for better selection of candidates suitable for adjuvant platinum-based therapy. “In the era of molecular classification, subsets of TNBC sensitive to PCb should be further investigated,” they added.