Rita Nanda, MD
Treatment with pembrolizumab (Keytruda) continued to show a consistent durable benefit with an additional year of follow-up for heavily pretreated patients with recurrent PD-L1-positive metastatic triple-negative breast cancer (TNBC), according to findings from the phase Ib KEYNOTE-012 trial presented at the 2016 San Antonio Breast Cancer Symposium.
In the updated findings, the median follow-up was 10.7 months and 2 patients had finished a complete 24-month course of pembrolizumab. The median progression-free survival (PFS) was 1.9 months (95% CI, 1.6-5.5) and the 12-month PFS rate was 17.8%. The median overall survival (OS) was 11.3 months (95% CI, 5.3-18.2) and the 12-month OS rate was 47.1%.
"The results of this study and others have demonstrated that breast cancer is an immunogenic cancer, and future studies are aimed at continuing to build on the early promise of immunotherapy in the management of breast cancer," Rita Nanda, MD, associate director, Breast Medical Oncology at the University of Chicago.
In the trial, 32 patients at a median age of 50.5 years (range, 29-72) received intravenous pembrolizumab at 10 mg/kg every 2 weeks. The median duration of treatment was 59.5 days (range, 1-723 days). The ECOG performance status was 1 for 53.1% of patients and 40.6% had elevated lactate dehydrogenase levels. Visceral metastases were present in 78.1% of patients and the median number of prior therapies for metastatic disease was 3 (range, 1-7).
In 27 assessable patients, the overall response rate was 18.5%, which included 1 complete response (CR; 3.7%) and four partial responses (PR; 14.8%). Additionally, seven patients had stable disease (SD; 25.9%), 1 of which persisted for ≥24 months.
The overall clinical benefit rate (CR + PR + SD ≥24 months) with pembrolizumab was 22.2% (95% CI, 8.6-42.3). Thirty-six percent of patients experienced a decrease from baseline in tumor size. Two patients continued to respond at the time of the analysis (128+ weeks).
The median time to response was 4.1 months and the median duration of response was not yet reached. Sixty percent of responses lasted ≥6 months (range, 3.4-26.3+ months) and 10% of patients remained progression-free by Kaplan-Meier estimates from 15 months until the longest duration of follow-up at 30 months, representing a tail on the curve.
The patient who experienced a CR discontinued therapy due to grade 2 treatment-related organizing pneumonia. The CR lasted 11 months while on therapy and for an additional 15 months after stopping treatment. For the patients who completed 24 months of pembrolizumab, the first had a persistent PR for 22.7 months and the other developed progressive disease and was retreated with pembrolizumab, leading to stable disease.
"While a minority of patients benefit from single agent pembrolizumab, those who do respond can benefit from treatment for prolonged periods of time, and can continue to benefit for months after treatment is discontinued," said Nanda.
Adverse events (AEs) of any grade occurred in 62.5% of patient treated with pembrolizumab, with grade 3/4 AEs occurring in 18.8% of patients. The most common AEs were arthralgia (18.8%), fatigue (18.8%), myalgia (18.8%), and nausea (18.8%). Grade ≥3 AEs, which occurred in 1 patient each, included anemia, aseptic meningitis, blood fibrinogen decrease, colitis, disseminated intravascular coagulation (grade 5), headache, lymphopenia, and pyrexia.
"Pembrolizumab is associated with a favorable side effect profile and long lasting responses," said Nanda. "Studies combining pembrolizumab with other forms of therapy—including chemotherapy, radiation therapy, and targeted therapy—aimed at increasing the proportion of patients who benefit from immunotherapy are ongoing."
The phase III KEYNOTE-119 trial is comparing single-agent pembrolizumab with physician's choice of chemotherapy as a second- or third-line treatment for metastatic TNBC (NCT02555657). Additionally, the phase III KEYNOTE-355 study is comparing pembrolizumab plus chemotherapy with chemotherapy and place as a frontline therapy for unresectable or metastatic TNBC (NCT02819518).
Nanda R, Specht J, Dees C, at al. KEYNOTE-012: Long-lasting responses in a phase Ib study of pembrolizumab for metastatic triple-negative breast cancer (mTNBC). Presented at: 2016 San Antonio Breast Cancer Symposium; December 6-10, 2016; San Antonio, TX. Abstract P6-10-03.<<< View more from the 2016 San Antonio Breast Cancer Symposium