The Efficacy of Maintenance Strategy in Triple-Negative Breast Cancer: An Analysis of KEYLYNK-009 Trial

Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer that lacks expression of estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 (HER2). Currently, there is a lack of targeted therapies for TNBC, making the exploration of maintenance strategies crucial for improving patient outcomes. In the phase II KEYLYNK-009 trial, a maintenance strategy involving checkpoint blockade and a PARP inhibitor was evaluated. While the safety profile was favorable, the trial did not demonstrate improved survival outcomes in unselected patients with TNBC. This article critically evaluates the trial and its implications for the management of TNBC.

The open-label KEYLYNK-009 study recruited patients with locally recurrent inoperable or metastatic TNBC who had responded or had stable disease following induction treatment with pembrolizumab and platinum-based chemotherapy. After a median follow-up of 17 months, the trial did not show significant differences in progression-free survival (PFS) or overall survival (OS) between patients who received maintenance pembrolizumab plus olaparib or continued with pembrolizumab plus chemotherapy. The respective median PFS values were 5.5 and 5.6 months, while the median OS values were 25.1 and 23.4 months.

Subgroup Analysis: BRCA Mutation and PD-L1 Status

A trend towards a more favorable PFS was observed with the chemotherapy-free strategy in the subgroup of patients with a BRCA mutation. The median PFS for this subgroup was 12.4 months with pembrolizumab plus olaparib compared to 8.4 months with pembrolizumab plus chemotherapy. This finding suggests that maintenance with pembrolizumab plus olaparib could be an effective strategy for patients with germline BRCA mutations receiving immunotherapy with induction chemotherapy, although confirmation in larger trials is needed.

In terms of PD-L1 status, patients with a combined positive score (CPS) of ≥10 did not demonstrate different OS rates between treatment arms. This indicates that the addition of a PARP inhibitor did not confer additional benefits in this subgroup of patients. It is worth noting that only 48% of the randomized patients had a PD-L1 CPS ≥10, suggesting that the majority of patients may not have derived significant benefit from pembrolizumab or pembrolizumab plus olaparib.

One of the notable findings of the KEYLYNK-009 trial was the lower incidence of treatment-related adverse events (TRAEs) in patients receiving pembrolizumab and olaparib compared to pembrolizumab and chemotherapy. This observation is clinically significant, as it suggests that the combination of pembrolizumab and olaparib may offer a more favorable side effect profile. In fact, the rate of grade ≥3 TRAEs was markedly lower with pembrolizumab and olaparib (33% vs. 68%).

Furthermore, the trial showed that in patients who had a great response or stable disease to induction chemotherapy with pembrolizumab, dropping chemotherapy in the maintenance setting and continuing with pembrolizumab alone did not impact outcomes. This finding is important as it challenges the current standard of care and suggests that pembrolizumab alone may be sufficient for maintenance therapy in selected patients.

The KEYLYNK-009 data provide reassurance to clinicians that both a PARP inhibitor and continued chemotherapy can be safely used as maintenance therapies with pembrolizumab. The slightly better side effect profile observed with olaparib suggests that it may be the preferred option in this setting. However, further research is needed to explore the possibility of using pembrolizumab alone for maintenance after a response to induction therapy with pembrolizumab and chemotherapy. This approach, while not currently the standard of care, is being implemented in clinical practice and warrants investigation in future studies.

The results of the KEYLYNK-009 trial do not support the use of a maintenance strategy involving pembrolizumab plus olaparib or chemotherapy for unselected patients with TNBC. The lack of significant improvements in PFS and OS suggests a need for more personalized approaches to treatment. Subgroup analyses have highlighted the potential benefits of pembrolizumab plus olaparib in patients with BRCA mutations. The favorable safety profile of pembrolizumab and olaparib compared to pembrolizumab and chemotherapy offers an alternative option for maintenance therapy. However, further research is required to optimize maintenance strategies and improve outcomes for patients with TNBC.

Health

Articles You May Like

The Impact of Melting Polar Ice Caps on Earth’s Rotation
The Endorsement of Donald Trump by Elon Musk in the Wake of a Rally Shooting
Analysis of the Effect of a GOP Sweep on Defense Stocks
The Tough Loss of England in Euro 2024

Leave a Reply

Your email address will not be published. Required fields are marked *