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. 2024;20(31):2343-2355.
doi: 10.1080/14796694.2024.2357534. Epub 2024 Jun 26.

OptimICE-RD: sacituzumab govitecan + pembrolizumab vs pembrolizumab (± capecitabine) for residual triple-negative breast cancer

Sara M Tolaney  1   2 , Angela DeMichele  3 , Toshimi Takano  4 , Hope S Rugo  5 , Charles Perou  6 , Filipa Lynce  1   2 , Heather Anne Parsons  1   2 , Cesar Augusto Santa-Maria  7 , Gabrielle Betty Rocque  8 , Wenliang Yao  9 , Shawn W Sun  9 , Simonetta Mocci  9 , Ann H Partridge  1   2 , Lisa A Carey  6
Affiliations

OptimICE-RD: sacituzumab govitecan + pembrolizumab vs pembrolizumab (± capecitabine) for residual triple-negative breast cancer

Sara M Tolaney et al. Future Oncol. 2024.

Abstract

Patients with early-stage triple-negative breast cancer (TNBC) with residual invasive disease after neoadjuvant therapy have a high risk of recurrence even with neoadjuvant and adjuvant treatment with pembrolizumab. Sacituzumab govitecan, a Trop-2-directed antibody-drug conjugate with a topoisomerase I inhibitor payload, improved progression-free survival (PFS) and overall survival (OS) versus chemotherapy in patients with pre-treated metastatic TNBC. Moreover, preclinical data suggest that topoisomerase I inhibitors may enhance the effects of immune checkpoint inhibitors through activation of the cGAS-STING pathway. Here we describe the international randomized phase III AFT-65/ASCENT-05/OptimICE-RD trial, which evaluates the efficacy and safety of sacituzumab govitecan plus pembrolizumab versus treatment of physician's choice (pembrolizumab ± capecitabine) among patients with early-stage TNBC with residual invasive disease after neoadjuvant therapy.Clinical Trial Registration: NCT05633654 (ClinicalTrials.gov)Other Study ID Number(s): Gilead Study ID: GS-US-595-6184Registration date: 1 December 2022Study start date: 12 December 2022Recruitment status: Recruiting.

Keywords: TNBC; adjuvant; pembrolizumab; residual invasive disease; sacituzumab govitecan; triple-negative breast cancer.

Plain language summary

AFT-65/ASCENT-05/OptimICE-RD is an ongoing clinical trial that is testing a new treatment combination for patients with stage II or III triple-negative breast cancer (TNBC). Stage II–III means the cancer is confined to the breast and/or nearby lymph nodes and can be surgically removed. However, there remains a risk that the cancer could recur after surgery. To reduce this risk, patients with stage II–III TNBC receive anti-cancer medication before and after surgery. For some patients, receipt of anti-cancer medication before surgery produces a pathologic complete response (pCR), meaning there is no observable cancer left behind at surgery. Patients with a pCR have a lower risk of recurrence than patients with residual disease.The AFT-65/ASCENT-05/OptimICE-RD trial includes people with stage II-III TNBC who have residual cancer after completing their course of pre-surgery anti-cancer medication. All participants have any remaining cancer in their breast and/or lymph nodes removed surgically, after which they are randomly assigned to receive one of two treatments. The experimental therapy consists of pembrolizumab along with a medication called sacituzumab govitecan, which kills cancer cells directly and may strengthen the anti-cancer immune response. Pembrolizumab strengthens the anti-cancer immune response, so the hypothesis of this trial is that the two medications will be more effective together. The control therapy consists of pembrolizumab, alone or in combination with a chemotherapy medication called capecitabine, which is the current standard of care. To study the effectiveness of each treatment, the researchers are following up with all participants to learn if and when their breast cancer returns.

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Conflict of interest statement

The authors have no competing interests or relevant affiliations with any organization or entity with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Figures

Figure 1.
Figure 1.
Primary hypothesis: Sacituzumab govitecan induces DNA damage, which results in STING activation and increased anti-tumor immunity. Efficacy will be synergistically enhanced through combination with pembrolizumab.
Figure 2.
Figure 2.
Study schema. BID: Twice daily; d: Day; dDFS: Distant disease-free survival; ER: Estrogen receptor; iDFS: Invasive disease-free survival; IV: Intravenous; OS: Overall survival; PO: Orally; PR: Progesterone receptor; QoL: Quality of life; RFS: Recurrence-free survival; ROW: Rest of world; TEAEs: Treatment-emergent adverse events; TIL: Tumor-infiltrating lymphocytes; TNBC: Triple-negative breast cancer; TOI: Trial outcome index; TTW: Time to worsening.
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