Proffered paper session: Breast Cancer, early stage

In this video, Dr Elisa Agostinetto discusses and comments on the data of some interesting studies presented at ESMO 2024 during the proffered paper session on early-stage breast cancer.  

The OptiTrain breast cancer trial focused on the role of exercise and physical activity in breast cancer patients, particularly those undergoing chemotherapy for early breast cancer. This trial addresses a growing area of interest in oncology, where exercise is increasingly recognised as a supportive therapy and a potential factor in improving prognosis and survival. In the trial, patients were randomised to engage in high-intensity training, which included either aerobic or resistance training or a control arm without structured exercise. The findings revealed that patients who participated in high-intensity exercise experienced significantly longer overall survival and a lower risk of breast cancer recurrence compared to those in the control group. While these results are promising, interpreting such trials can be challenging due to potential biases and confounding factors, such as patient motivation or other lifestyle variables. Nevertheless, the findings are very relevant to clinical practice, as exercise is a simple, low-cost intervention that can be easily recommended to patients and may offer substantial benefits for both physical well-being and cancer outcomes. This trial supports the growing evidence that physical activity could play a meaningful role in breast cancer treatment strategies.

The Neo-CheckRay trial, sponsored by the Institute Jules Bordet, investigated an innovative treatment strategy for patients with luminal B high-risk early breast cancer, a type of breast cancer typically characterised as immunologically cold. The trial tested a combination of radiation therapy on the primary tumour, with or without durvalumab and with or without oleclumab, an anti-CD73, all integrated into a neoadjuvant chemotherapy regimen.

The study included three arms: Arm 1 (Control): Radiation therapy on the primary tumour plus chemotherapy. 

Arm 2: Radiation therapy plus chemotherapy and durvalumab. And Arm 3: Radiation therapy plus chemotherapy, durvalumab, and oleclumab.

The trial’s primary endpoint was the proportion of patients achieving Residual Cancer Burden (RCB) 0/1 after surgery, with pathologic complete response (pCR) as a secondary endpoint. It’s important to note that the radiation therapy was not intended to be ablative but aimed at stimulating an immune response. The findings of the trial were quite intriguing. All three arms showed a much higher-than-expected proportion of RCB 0/1, suggesting that the combination therapies were more effective than anticipated. Although the study didn’t formally meet its primary endpoint, the results highlighted a synergistic effect between the immune-stimulating radiotherapy and the immunotherapy, especially in patients with PD-L1 negative tumours—the “coldest” subgroup of luminal B tumours from an immunological perspective. In this PD-L1 negative group, the difference in pCR rates between the patients receiving only radiation and chemotherapy (Arm 1) and those also receiving immunotherapy (Arms 2 and 3) was striking. The pCR rate was significantly higher, nearly ten times higher, in the arms where immunotherapy was added. This suggests that combining radiation therapy with immunotherapy may offer a promising new strategy for treating immunologically cold luminal B breast cancers.

The NATALEE trial, a phase III randomised study, was one of the most anticipated presentations at ESMO 2024. It provided important updates on the use of adjuvant ribociclib combined with standard endocrine therapy in patients with high-risk hormone receptor-positive, HER2-negative early breast cancer. The latest data presented focused on the four-year outcomes of the trial, adding another year of follow-up to the previously reported three-year results.

At three years, the NATALEE trial had already shown a significant improvement in invasive disease-free survival (iDFS) by adding ribociclib to standard endocrine therapy compared to endocrine therapy alone. This presentative at ESMO confirmed and extended those findings, with a 4.9% difference in iDFS between the two arms at four years (up from 2.7% at three years). This demonstrates that the curves continue to separate, indicating an ongoing and increasing benefit with the extended follow-up period. In addition to the iDFS benefit, the trial also reported a significant improvement in distant disease-free survival (DDFS), which is particularly important for preventing metastases. However, data on OS remains immature at this stage, so no conclusions can yet be drawn regarding OS. These findings further support the benefit of adding ribociclib to endocrine therapy in patients with stage II and III hormone receptor-positive, HER2-negative early breast cancer, a group known for having a higher risk of recurrence. However, these results also raise new questions, particularly when it comes to selecting between ribociclib and abemaciclib, another CDK4/6 inhibitor, for adjuvant therapy. As eligibility criteria for the two agents overlap in certain patient populations, clinicians must carefully consider how to choose between these treatments. Overall, the NATALEE trial provides highly significant data that could lead to more effective treatment strategies, offering better long-term outcomes for patients with high-risk early breast cancer.