Dr Armaghani on the Investigation of De-Escalated Treatment Approaches in TNBC

Avan Armaghani, breast medical oncologist, Moffitt Cancer Center, discusses the feasibility of de-escalating treatment in triple-negative breast cancer (TNBC), as well as planned or ongoing research investigating this approach in the neoadjuvant and metastatic settings.

The evolving treatment landscape in breast cancer, particularly in TNBC, is marked by a concerted effort to minimize the use of anthracycline-based chemotherapy while maintaining or improving patient outcomes, Armaghani begins. This may be accomplished by utilizing immunotherapy plus a non–anthracycline-based regimen, substituting anthracycline with antibody drug conjugates (ADCs), or other alternative approaches, Armaghani suggests.

Studies conducted in both the neoadjuvant and metastatic settings are at the forefront of these endeavors, Armaghani states. For instance, the phase 2 NeoPACT study (NCT03639948) investigated neoadjuvant pembrolizumab (Keytruda), carboplatin, and docetaxel followed by surgery and adjuvant therapy as per provider's discretion, Armaghani details. Findings from the single-arm trial were presented at the 2022 ASCO Annual Meeting, and showed that the experimental combination produced a pathologic complete response rate of approximately 58% in the overall population and a 2-year disease-free survival (DFS) rate of 89% in the overall population. These data illustrate the potential efficacy of neoadjuvant chemoimmunotherapy in TNBC.

Looking to the future, ongoing studies such as the phase 2 NeoSTAR trial(NCT04230109) are exploring the use of the ADC sacituzumab govitecan-hziy (Trodelvy) alone or in combination with pembrolizumab, Armaghani continues. Thus far, findings from this study have shown high response rates with single-agent sacituzumab govitecan in patients with localized TNBC.

Additionally, the phase 3 SCARLET/SWOG-2212 trial (NCT05929768) will compare the NeoPACT regimen, which excludes anthracycline, with the KEYNOTE-522 regimen, which combines anthracycline-based chemotherapy with pembrolizumab, she says. The trial aims determine the most effective treatment strategy in the early-stage setting, Armaghani explains.

In the metastatic setting, efforts to de-escalate therapy continue with studies such as the phase 3 ASCENT-03 trial (NCT05382299) comparing sacituzumab govitecan with the physician's choice of treatment in previously untreated patients with metastatic TNBC, Armaghani says. This study is exploring the possibility of using sacituzumab govitecan as a first-line therapy option, she notes. The phase 3 ASCENT-04 trial (NCT05382286) is another study evaluating sacituzumab govitecan in combination with pembrolizumab versus the physician's choice of treatment alongside pembrolizumab, Armaghani adds.

The results from these trials have the potential to reshape the treatment paradigm in TNBC by offering alternative therapies that can potentially replace or reduce the use of anthracyclines, thereby improving the overall experience and outcomes for TNBC patients, Armaghani concludes.