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Paolo Tarantino, MD The treatment paradigm for HER2-positive breast cancer continues to evolve with a growing emphasis on anthracycline-sparing approaches and the refinement of initial strategies in both the early-stage and metastatic settings, according to Paolo Tarantino, MD. "I do feel the future will have more and more anthracycline-sparing [regimens], acknowledging that there are few selected populations of patients that may still benefit from anthracyclines, such as those in whom HER2 positivity remains unclear, HER2-positive pregnant patients, and those with inflammatory breast cancer," Tarantino said. In an interview with OncLive ® , Tarantino discussed the growing trend of avoiding anthracycline-containing regimens in the management of HER2-positive breast cancer; highlighted the enduring influence of the phase 3 CLEOPATRA trial (NCT00567190), which established trastuzumab (Herceptin), pertuzumab (Perjeta), and docetaxel (THP) as the standard first-line regimen in the metastatic setting; and detailed how THP has evolved over the past decade with alternative taxanes, endocrine therapy, and, most recently, CDK4/6 inhibitors.
Tarantino is a breast medical oncologist at Dana-Farber Cancer Institute in Boston, Massachusetts, and a researcher at the University of Milan in Italy. Tarantino : Anthracyclines and taxanes have never really been directly compared because anthracyclines came first, and taxanes were subsequently added to anthracyclines. However, [recently] in HER2-positive breast cancer [management], we've been trying to spare anthracyclines as much as possible, mostly because of the long-term [adverse] effects of these type of drugs.
They are highly effective, but they can cause cardiac dysfunction—even years after treatment—and secondary leukemia, which are rare, but can be life threatening. This is why several attempts were made to develop regimens that would not include anthracyclines, and then use only taxanes or replace them with platinum compounds. In truth, if you look at the current National Comprehensive Cancer Network Guidelines, the main treatment recommended for most patients with stage II and III, HER2-positive breast cancer is neoadjuvant docetaxel and carboplatin with dual HER2 blockade.
For patients with stage I disease, we mostly utilize paclitaxel, trastuzumab, or ado-trastuzumab emtansine [T-DM1; Kadcyla]. We are not using that much anthracycline anymore, mostly because taxanes combined with the HER2 blockade are extremely effective, and we do expect more data, hopefully coming soon, from the [phase 2] COMPASSHER2-pCR trial [NCT04266249], where patients received only 12 weeks of trastuzumab, and if they have a pathologic complete response, they can avoid any further stereotaxic treatment. [When] talking [about] first-line treatments for metastatic HER2-positive breast cancer, we have to acknowledge that there is a trial conducted more than 10 years ago now that really has set the standard of care for a long time: CLEOPATRA.
In 2012, the phase 3 CLEOPATRA trial changed the way we treat patients with metastatic, HER2-positive breast cancer in the first-line setting by adding pertuzumab—a second HER2 antibody—to trastuzumab and docetaxel, and that THP regimen was extremely effective. After a few months of chemotherapy, you drop the chemotherapy, and the patient could just receive HER2 blockade, so [it was also an] extremely well-tolerated regimen. In the last 10 years, we have further refined [this approach] in several ways.
First, phase 3 PERUSE study [NCT01572038] compared different types of taxanes and found that paclitaxel was equally effective compared with docetaxel, and nab-paclitaxel [Abraxane] was also an option, so that allowed us to optimize the taxane backbone. There were [also] other trials showing that endocrine treatment could be important in this setting when combined with THP, and more recently, that eribulin would be as effective as a taxane when combined with HP, allowing us to give the patient first-line THP with different toxins or eribulin. The most recent update in the field has been adding a CDK4/6 inhibitor in the maintenance space.
There was a trial presentation at the 2024 San Antonio Breast Cancer Symposium of the phase 3 PATINA trial [NCT02947685] showing that palbociclib [could also be added as maintenance]. [This trial enrolled] patients with estrogen receptor–positive and HER2-positive disease, [and] the medium progression-free survival with this treatment strategy reached up to 44 months, which was outstanding. Here we're talking almost 4 years on first-line treatment for triple-positive metastatic breast cancer.
We still use the same treatment strategy CLEOPATRA developed a decade ago, but we’ve made it better, and we do expect to further improve this with some upcoming trials [in the future]..
