A recent phase II trial, KEYLYNK-009, explored the efficacy of a maintenance strategy involving a checkpoint blockade and a PARP inhibitor for patients with triple-negative breast cancer (TNBC). Unfortunately, the results indicated that this approach did not improve survival outcomes for unselected patients with TNBC. Despite the disappointing findings, the trial did demonstrate a good safety profile for the treatment regimen.
The participants in the study were patients with locally recurrent inoperable or metastatic TNBC who had responded or had stable disease following induction treatment with pembrolizumab and platinum-based chemotherapy. The median follow-up period was 17 months. The trial aimed to assess the progression-free survival (PFS) and overall survival (OS) of patients who received maintenance pembrolizumab plus olaparib or continued with pembrolizumab plus chemotherapy.
The analysis of the data revealed that the PFS and OS were essentially the same for both groups. The median PFS for those receiving maintenance pembrolizumab plus olaparib was 5.5 months, while it was 5.6 months for those continuing with pembrolizumab plus chemotherapy. The HR for PFS was 0.98, suggesting no significant difference between the two groups. Similarly, the median OS was 25.1 months in the pembrolizumab plus olaparib arm and 23.4 months in the pembrolizumab plus chemotherapy arm, with an HR of 0.95.
Dr. Hope Rugo, who presented the findings, emphasized the importance of considering the previous duration of induction chemotherapy when interpreting the results. The patients in the trial had already received a median of 4.2 months of induction chemotherapy, which was not included in the PFS and OS numbers. This factor may have influenced the outcomes of the trial.
Although the overall results showed no significant difference in survival outcomes between the two groups, a trend toward a more favorable PFS was observed in the subgroup of patients with a BRCA mutation. In this subgroup, the median PFS for those receiving pembrolizumab plus olaparib was 12.4 months, compared to 8.4 months for those continuing with pembrolizumab plus chemotherapy. However, this finding requires confirmation in larger trials before conclusions can be drawn.
One positive aspect of the trial was the good safety profile for both treatment regimens. Patients receiving pembrolizumab and olaparib experienced fewer treatment-related adverse events (TRAEs), especially grade 3 or higher TRAEs, compared to those receiving pembrolizumab and chemotherapy. The incidence of immune-mediated adverse events was similarly low in both groups. Additionally, treatment discontinuation due to TRAEs was less common in the olaparib arm.
Dr. Allison Kurian, an expert in the field, noted that the trial’s results provide reassurance for clinicians in their choices for maintenance therapy. The trial demonstrated that both a PARP inhibitor and continuing chemotherapy with pembrolizumab are viable options, with olaparib showing a slightly better side effect profile. Kurian suggested that future studies could explore the use of pembrolizumab alone for maintenance therapy after a positive response to induction therapy with pembrolizumab and chemotherapy. While it is not yet a standard of care, dropping chemotherapy in favor of pembrolizumab alone is a practice already seen in some clinics.
Leave a Reply