Rapid Fire Session 3

In this video, Dr Lefèvre comments on the data of some interesting studies presented during the Rapid Fire Session  3 at SABCS 2024.

The first study examined a new neoadjuvant therapy combining the checkpoint inhibitor dostarlimab with the PARP inhibitor niraparib for patients with HER2-negative breast cancer who have germline BRCA or PALB2 mutations. This was part of a three-arm study, with Arm C focusing on ER+/HER2- patients. Participants received 18 weeks of this combination therapy, followed by surgery. A biopsy was mandatory at baseline, after the second cycle, and post-surgery. Patients who showed inadequate responses were allowed to switch to chemotherapy. The primary aim was to measure the pCR rate and assess changes in tumour-infiltrating lymphocytes (TILs). The results showed a pCR rate of 18.7% and 44.4% of patients achieving a Residual Cancer Burden (RCB) score of 0 or 1, indicating good responses in some patients. Common side effects included rash, ALT elevation, and nausea, consistent with this class of treatment. Importantly, the therapy led to an increase in TILs by 11.9%, and patients with higher TIL levels at baseline were more likely to achieve a pCR. These findings highlight the potential of non-chemotherapy, targeted approaches for ER-positive breast cancer, but more research is needed to confirm these early results.

The second study provided an analysis of biomarkers from the A-BRAVE trial, a phase III study evaluating the use of adjuvant avelumab versus observation in high-risk triple-negative breast cancer patients. An earlier presentation at ASCO 2024 showed that although the co-primary endpoints for DFS in the ITT population were not met, there was a notable improvement in three-year OS and distant DFS. The biomarker analysis focused on PD-L1 status, TIL percentage, and RCB. PD-L1 was assessed in the pre-treatment biopsy, while TILs and RCB were evaluated in the surgical specimens. Results showed that higher PD-L1 expression correlated with better prognoses, but patients with low PD-L1 expression derived the most benefit from avelumab. Similarly, patients with poor prognostic indicators, such as higher RCB scores or lower TIL levels, experienced a greater therapeutic benefit from the immunotherapy. This analysis underlines the potential value of tailoring triple-negative breast cancer treatment based on biomarker profiles to maximize therapeutic outcomes.

The third study discussed the neoHIP trial, which explored the addition of pembrolizumab to neoadjuvant HER2-targeted therapy in early HER2+ breast cancer. The trial enrolled patients with stage II or III disease and randomised them into three arms. One arm received the standard combination of paclitaxel, trastuzumab, and pertuzumab (THP), another added pembrolizumab to this regimen, and a third arm replaced pertuzumab with pembrolizumab. The study aimed to evaluate the pCR rates, and it found that adding pembrolizumab to the THP regimen increased the pCR rate by 18.9%, which is considered clinically meaningful. Safety outcomes were similar across the groups, with low rates of immune-related adverse events and no severe complications. The third arm, which lacked dual HER2-targeted therapy, was closed early due to inferior outcomes, emphasising the necessity of using both trastuzumab and pertuzumab. This is the first trial to show that adding immunotherapy to dual HER2-targeted therapy improves outcomes in early HER2+ breast cancer, setting a foundation for further research in this area.

The fourth study presented the results of an Alliance trial, which aimed to prevent radiation dermatitis in patients undergoing post-mastectomy radiotherapy using a Mepitel film. Radiation dermatitis is a common and uncomfortable side effect of treatment that affects patients’ quality of life, particularly in those receiving extensive radiotherapy. The study compared the use of a novel Mepitel film to the standard institutional approach. The Mepitel film was applied before the start of radiation therapy and replaced weekly. The severity of dermatitis was assessed using the RISRAS scale, which includes both patient-reported symptoms like pain and burning and physician-observed signs like redness or necrosis. Results showed that the film significantly reduced the severity of dermatitis, with improvements observed during treatment and persisting for weeks afterwards. Importantly, oncologic outcomes were unaffected, indicating the film’s safety. This simple intervention could represent a new standard of care, providing a practical and effective way to reduce a common side effect of radiotherapy.