Pembrolizumab plus chemotherapy extends survival in triple-negative breast cancer subset
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- Researchers report nearly 7-month increase in median OS among patients with a PD-L1 CPS of 10 or higher.
- Safety consistent with previous analyses.
- Immunotherapy class “marks the continued improvement of breast cancer treatment.”
The addition of pembrolizumab to first-line chemotherapy significantly prolonged OS compared with chemotherapy alone among a subgroup of patients with inoperable or metastatic triple-negative breast cancer, according to study results.
Findings of the phase 3 KEYNOTE-355 trial, published in The New England Journal of Medicine, showed the OS benefit specifically among patients with tumors that expressed PD-L1 with a combined positive score (CPS) of 10 or higher.
Rationale and methods
As Healio previously reported, the KEYNOTE-355 trial included 847 patients (median age, 53 years; 68% white) with previously untreated, locally recurrent inoperable or metastatic disease whose tumors expressed PD-L1.
Javier Cortes, MD, PhD, head of the breast cancer program at IOB Institute of Oncology in Spain, and colleagues randomly assigned 566 women to 200 mg pembrolizumab (Keytruda, Merck) every 3 weeks plus investigator’s choice of chemotherapy, including nab-paclitaxel (Abraxane, Celgene), paclitaxel or gemcitabine/carboplatin, for up to 35 administrations. The other 281 patients received chemotherapy alone.
In the final OS analysis, Cortes and colleagues reported outcomes in subgroups of patients with PD-L1 CPS of 10 or higher (CPS-10 subgroup), a PD-L1 CPS of 1 or higher (the CPS-1 subgroup) and in the intention-to-treat population.
Median follow-up was 44.1 months.
Key findings
Results showed median OS of 23 months with the pembrolizumab combination vs. 16.1 months with chemotherapy alone (HR = 0.73; 95% CI, 0.55-0.95) among those in the CPS-10 group.
For those in the CPS-1 group, median OS was 17.6 months with pembrolizumab vs. 16 months with chemotherapy alone (HR = 0.86; 95% CI, 0.72-1.04), and median OS in the intention-to-treat group was 17.2 months vs. 15.5 months (HR = 0.89; 95% CI, 0.76-1.05).
No new safety signals were reported.
Implications
Cortes and colleagues’ findings confirm the association between PD-L1 expression and pembrolizumab that they observed in preclinical and clinical studies — “a finding that completes the bench-to-bedside cycle,” according to an accompanying editorial by Xavier Pivot, MD, PhD, oncologist at Institute of Cancerology Strasbourg in Strasbourg, France.
“This new class of immunotherapy is integral to the success of biologic agents and marks the continued improvement of breast cancer treatment. Other immunotherapies will emerge, but pembrolizumab will remain the first treatment shown to prolong OS, a welcome and definitive change in the treatment of a subgroup of women with advanced triple-negative breast cancer,” Pivot wrote.
References:
- Cortes J, et al. N Engl J Med. 2022;doi:10.1056/NEJMoa2202809.
- Pivot X, et al. N Engl J Med. 2022;doi:10.1056/NEJMe2207532.
Perspective
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Megan Kruse, MD
The initial findings from KEYNOTE-355 showing an improvement in PFS for patients with advanced PD-L1-positive, ER-negative, PR-negative, HER2-negative breast cancer when treated with the combination of pembrolizumab and chemotherapy compared with standard chemotherapy alone were enough to be practice changing on their own given the overall poor outcomes in this patient population.
The statistically significant and clinically meaningful approximately 7-month improvement in OS now demonstrated only serves to solidify pembrolizumab’s place in the first-line treatment setting for these patients.
Because the benefit of immunotherapy is limited to patients with PD-L1-positive disease — specifically those with CPS 10 or higher — upfront knowledge of a patient’s PD-L1 status is as crucial as ER/PR/HER2 results when counseling patients about treatment options. As such, a clear workflow for PD-L1 testing should be prioritized with pathology so results are not delayed.
If PD-L1 results are unavailable at time of consultation and treatment needs to be started urgently, it is reasonable to select one of the chemotherapy partner options from KEYNOTE-355 such that pembrolizumab can then be added if PD-L1 testing results indicate potential benefit.
I often am asked if there is any preference among the chemotherapy partner options for this regimen. The short answer is no. This decision must take into account any prior chemotherapy received for breast cancer, the disease-free interval, patient fitness/comorbidities and patient preferences. In practical terms, I generally will select a taxane-based regimen for patients with de novo disease, those with no prior exposure to this class of chemotherapy or those with long disease-free interval from taxanes (certainly more than 1 year, but preferable more than 2 years) and use the carboplatin/gemcitabine backbone for those with more recent prior taxane exposure.
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