KEYNOTE-028 results point to pembrolizumab efficacy in SCLC, nasopharyngeal cancer
medwireNews: Findings from the multicohort, phase Ib KEYNOTE-028 trial indicate that pembrolizumab elicits durable responses and is well tolerated in patients with extensive-stage small-cell lung cancer (SCLC) and those with recurrent or metastatic nasopharyngeal carcinoma.
Patrick Ott (Dana-Farber Cancer Institute, Boston, Massachusetts, USA) and co-researchers report the results of the SCLC cohort, which included 24 patients with programmed cell death ligand 1 (PD-L1)-positive disease, defined as PD-L1 expression on at least 1% of tumor or inflammatory cells or positive staining in the stroma. The majority (87.5%) had received at least two prior lines of therapy.
Over a median follow-up of 9.8 months, treatment with the programmed cell death protein 1 inhibitor at a dose of 10 mg/kg every 2 weeks induced a complete response in one patient, while seven achieved a partial response, giving an objective response rate (ORR) of 33.3%.
As reported in the Journal of Clinical Oncology, responses were observed at a median of 2.0 months and lasted for a median duration of 19.4 months. At the time of analysis, three patients continued to receive and respond to pembrolizumab.
Two-thirds (66.7%) of patients had an adverse reaction to pembrolizumab, with two patients experiencing events of grade 3 or worse, one a grade 3 case of bilirubin elevation and the other grade 3 asthenia and grade 5 colitis and intestinal ischemia. One patient experienced an immune-related adverse event, namely grade 2 autoimmune thyroiditis.
On the whole pembrolizumab was well tolerated and “the safety was consistent with the reported safety profile in other tumor types,” the researchers say.
In conclusion, they note that building on these initial promising results, multiple trials have been initiated to better define biomarkers of response and improve the efficacy of the drug “by moving treatment with pembrolizumab to the front-line and maintenance settings, as well as to combinations with chemotherapy, radiotherapy, and other immune-modulating agents.”
The findings of the nasopharyngeal cancer cohort were reported in the same journal, by a team led by Chiun Hsu, from the National Taiwan University Hospital in Taipei.
A total of 27 patients with PD-L1-expressing (positivity in ≥1% of tumor or tumor-infiltrating cells), locally advanced or metastatic disease received pembrolizumab at the same dose and were followed up for a median of 20 months. The study population was heavily pretreated, with 70.4% having received at least three previous lines of therapy for advanced disease.
No patient had a complete response to single-agent pembrolizumab, but seven had a partial response, which equated to an ORR of 25.9%.
Again, the responses tended to be rapid and durable, with a median time to response of 1.9 months and a median duration of response of 17.1 months.
Any grade treatment-related toxicities were observed in 74.1% of study participants, with 29.6% experiencing events of at least grade 3. Drug-related side effects of immune etiology – specifically, proteinuria, pneumonitis, and hepatitis – led to discontinuation in three patients.
Describing the safety profile as “manageable,” Hsu et al conclude that pembrolizumab monotherapy is a promising option for these patients “for whom therapeutic options are limited and who have a generally poor outcome.”
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