medwireNews: The addition of atezolizumab to neoadjuvant carboplatin and nab-paclitaxel does not significantly increase the rate of pathologic complete response (pCR) among women undergoing surgery for treatment-naïve triple-negative breast cancer (TNBC), research suggests.
The NeoTRIP trial included 280 patients with early high-risk (T1cN1; T2N1; T3N0) or locally advanced (T3N1; T4a, b, c; T4d any N; any T and N2–3) TNBC. Around half had PD-L1 positive tumors (56%) and locally advanced disease (49%), while 88% had positive axillary nodes.
The participants were randomly assigned to receive atezolizumab 1200 mg on day 1 and neoadjuvant carboplatin AUC2 and nab-paclitaxel 125 mg/m2 on days 1 and 8 of a 3-week cycle (n=138) or the same regimen without atezolizumab (n=142). Both groups received eight cycles prior to surgery followed by four cycles of adjuvant anthracycline.
The secondary endpoint of pCR, defined as the absence of invasive tumor cells in breast and lymph nodes, did not significantly differ between patients given atezolizumab and controls, at 48.6% versus 44.4%, write the researchers in the Annals of Oncology.
In multivariate analysis, those with PD-L1-positive tumors were a significant 2.08 times more likely to have a pCR than those with PD-L1-negative tumors. However, atezolizumab use and disease stage were not significantly associated with pCR.
Subgroup analyses revealed a significantly higher pCR rate among women with PD-L1-positive tumors (≥1%) relative to those with PD-L1-negative tumors, with respective rates of 59.5% and 33.9% after having received atezolizumab, although a similar nonsignificant trend was also found in the PD-L1-positive and -negative control arms (51.9 vs 35.4%).
When PD-L1 positivity was categorized by number of immune cells, there was a trend toward higher rates of pCRwith greater PD-L1 expression. Indeed, atezolizumab-treated patients who had strong PD-L1 expression (≥5%) had a rate of 71.4% compared with 33.9% among those without PD-L1 expression (<1%; significant odds ratio [OR]=4.87). Those with weak PD-L1 expression (≥1 to <5%) had a pCR rate of 52.9%, still higher than those without PD-L1 expression (significant OR=2.19).
The researchers point out that although the “[t]reatment-related adverse events were similar with either regimen,” the incidence of serious adverse events was significantly higher among those who did versus did not receive atezolizumab, at respective rates of 18% and 6%. Specifically, the atezolizumab group experienced a significantly higher incidence of liver transaminase abnormalities than the chemotherapy alone group, at both any-grade (38 vs 18%) and grade 3 (8% vs 1%).
“In summary, the present analysis of NeoTRIP shows that atezolizumab with nab-paclitaxel and carboplatin was feasible but did not improve the antitumour activity of chemotherapy measured as clinical response and as pCR rate in women with TNBC,” say the study authors.
However, they note that some earlier trials of immune checkpoint inhibitors – including KEYNOTE-522 and GeparNuevo – did not find pCR to predict event-free survival (EFS).
They add that “the primary endpoint of NeoTRIP is EFS, and the lack of pCR improvement may be misleading as to the impact of atezolizumab on efficacy and survival in high-risk TNBC.”
Luca Gianni (Fondazione Michelangelo, Milan, Italy) and colleagues conclude: “Continuing follow up for the event-free survival is ongoing, and molecular studies are under way.”
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Ann Oncol 2022; doi:10.1016/j.annonc.2022.02.004