PracticeUpdate: Haematology & Oncology

CONFERENCE COVERAGE 16

Pembrolizumab yields long-lasting responses inmetastatic triple-negative breast cancer P embrolizumab has been shown to provide long-lasting responses in patients with metastatic triple- negative breast cancer, reports the phase 1b KEYNOTE-012 study. and PD-L1–positive tumours (defined as expression in stroma or ≥ 1% of tumour by immunohistochemistry using the 22C3 antibody) received pembrolizumab 10 mg per kilogram of body weight every 2 weeks for 2 weeks or until disease progression or unacceptable toxicity.

discontinued pembrolizumab 11 months after achieving a complete response and has remained in complete response for approximately 15 months without receiving additional anticancer treatment. Two patients with a partial response discontinued pembrolizumab after completing 2 years of treatment. The first patient has maintained response for 22.7 months; the second patient experienced disease progression after 7.7 months. The median duration of response has not been reached (range 15 to at least 58 weeks). Thirty (93.8%) patients discontinued pembrolizumab: 27 (84.4%) for progressive disease and three (9.4%) for adverse events before reaching 2 years of treatment. Six (18.8%) patients experienced grade 3–5 treatment-related adverse events. One treatment-related death occurred (disseminated intravascular coagulation with decreased blood fibrinogen). Dr Nanda concluded that pembrolizumab was shown to provide long-lasting responses in patients with metastatic triple-negative breast cancer. Twenty-two percent of patients were alive at 2 years, supporting further development of the drug in heavily pretreated patients who experience a poor prognosis. The phase 2 KEYNOTE-086 study is ongoing and is evaluating efficacy and safety of single pembrolizumab as later-line treatment for metastatic triple-negative breast cancer.

Rita Nanda, MD, of the University of Chicago Medical Center, explained that in the multicentre, multicohort, nonrandomised phase 1b KEYNOTE-012 study, the anti- programmed death-1 (PD-1) antibody pembrolizumab demonstrated promising antitumour activity (18.5% objective response rate in patients with measurable disease at baseline, based on Response Evaluation Criteria in Solid Tumors v1.1 and assessed by central radiology review). As later-line therapy in previously treated patients with PD-1–ligand 1–positive metastatic triple-negative breast cancer, the progression-free survival rate was 24% and 12-month overall survival rate 43.1%. The toxicity profile was manageable. Dr Nanda presented updated follow-up data for KEYNOTE-012. Patients ≥ 18 years of age with oestrogen and progesterone receptor-negative, HER2- negative, recurrent or metastatic breast cancer, measurable disease per Response Evaluation Criteria in Solid Tumors v1.1, Eastern Cooperative Oncology Group performance status 0–1, any number of prior systemic treatments in the metastatic setting,

however, have not been defined. Dr Cuni reviewed the use of nephron-sparing surgery in 33 patients of a total of 216 patients operated for renal tumours in a cohort study from 2000 through 2015. The records of all patients were reviewed. All patients exhibited a single renal mean tumour size 3.6 cm (range 3.2–4.3) and a normal contralateral kidney. In Dr Cuni’s series, this size corresponded to 26% of partial nephrectomies. In other series, this size corre- sponded to 20–32% of partial nephrectomies. Thirty-three nephron-sparing surgeries were performed in 216 patients (16 female and 17 male). Mean patient age was 49 ± 9.5 years, and the surgery was elective in all. In 19 patients, lesions were located in the upper pole, 13 in the lower pole. One case was in a mesorenal location. The open approach was Response was assessed every 8 weeks by central radiology review per Response Evaluation Criteria in Solid Tumors v1.1. Survival was assessed every 3 months. Overall survival was estimates using the Kaplan- Meier method. Of the 32 female patients (median age 50.5 years, range 29–72 years) enrolled, 46.9% had received at least three lines of therapy, and 25.0% had received at least five lines of therapy for metastatic disease. The duration of median follow-up was 10.7 months (range 0.4–32.7). Median overall survival was 10.2 months (95% CI 5.3–17.5). Twelve-month overall survival was 41.1%. Twenty-five (78.1%) patients had died as of the data cutoff. Median progression-free survival was 1.9 months (95% CI 1.3–4.3); and the 12-month progression-free survival rate was 15.0%. Of the five responders (one complete and four partial responders) three have had long-lasting benefit from pembrolizumab. The patient with a complete response

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Nephron-sparing surgery can be performed safely and withmaximum preservation of renal function O pen nephron-sparing surgery and laparoscopic radical nephrectomy are relatively recent, significant develop- used in all cases. Mean tumour size was 3.6 cm (range 3.2–4.3).

Pathologic findings demonstrated renal cell carcinoma in 30 cases and benign lesions in three patients (9%). One patient experienced delayed bleeding for 2 days, and subsequent nephrectomy was performed. In that case, the tumour was 4.3 cm with mesorenal location. Subsequent nephrectomy was positive for a residual renal cell carcinoma tumour. Ultrasonography was performed 1–3 months postoperatively. Contrast-enhanced CT and MRI were performed subsequently every 6 months for 2 years and then yearly. Radiologi- cal investigations showed no local recurrence or metastasis. None of these patients devel- oped a tumour in the contralateral kidney after nephron-sparing surgery. Mean follow-up examination incorporating

ments for treating renal tumours and represent acceptable standards of care in cases of small renal mass and normal contralateral kidney, report results of a retrospective, single-cen- tre review. X. Cuni, MD, of the University of Pristina, Kosovo, explained that conservative renal sur- gery has become the gold standard treatment of small and peripheral malignant kidney lesions, cases of reduced renal function, and bilateral lesions. Nephron-sparing surgery provides effective therapy in patients with solitary sporadic renal tumours ≤ 4 cm and in the presence of normal contralateral kidney or an anatomi- cally functional solitary kidney. The optimal selection criteria for nephron-sparing surgery,

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