Top news of the week in oncology, and cancer drug development.
ASCO Recommends Standard Lumpectomy Margin Width for DCIS
A 2-mm margin should be the standard for patients with ductal carcinoma in situ who are undergoing breast conserving surgery with whole breast irradiation, according to a new guideline jointly released by ASCO, ASTRO, and the Society of Surgical Oncology. The guideline was designed to provide clarity regarding the optimal negative margin width for DCIS—a disease that accounts for approximately 20% of breast cancer cases.
It was also designed to limit patients from undergoing unnecessary surgery while simultaneously reducing healthcare costs. For negative margin widths, the guideline recommendations state that margins of at least 2 mm are associated with a reduced risk of ipsilatereal breast tumor recurrence (IBTR). Evidence does not support the routine practice of obtaining negative margin widths wider than 2 mm, the panelists stated in the guideline. Additionally, the recommendations state that a positive margin, defined as ink on DCIS, is associated with a significant increase in IBTR that is not nullified through WBRT.
See more on the guideline: http://www.onclive.com/web-exclusives/asco-recommends-standard-lumpectomy-margin-width-for-dcis
FDA Finally Approves Granisetron for CINV
The FDA has approved an extended release injection formulation of granisetron for use in combination with other antiemetic therapies for the prevention of chemotherapy-induced nausea and vomiting. The novel formulation of the 5-HT3 receptor antagonist can maintain therapeutic levels of granisetron for 5 or more days.
The approved indication is specifically for the prevention of acute and delayed nausea and vomiting associated with initial and repeat courses of moderately emetogenic chemotherapy or anthracycline and cyclophosphamide combination chemotherapy regimens. The efficacy data supporting the approval of extended release granisetron came from a multicenter double-blind trial that included 733 patients who received MEC or AC combination chemotherapy.
The results demonstrated that the granisetron formulation was noninferior to palonosetron. Among patients receiving MEC the CR in the acute phase was 83% in the granisetron arm compared with 89% in the palonosetron group. The CR rates in the delayed phase were 69% and 70%, respectively. Among patients who received AC combination chemotherapy, the CR rate in the acute phase for the granisetron group was 70% compared with 64% with palonosetron. The CR rates in the delayed phase were 50% versus 47%, respectively.
Venetoclax Shows Single-Agent Activity in AML
Treatment with single-agent BCL-2 inhibitor venetoclax demonstrated an overall response rate of 19% with a tolerable safety profile in patients who were unfit for intensive chemotherapy for those with relapsed/refractory acute myeloid leukemia. In the single-arm phase II study, the ORR achieved by patients consisted of 2 (6%) complete responses and 4 (13%) CRs with incomplete blood count recovery.
Additionally, 19% of patients treated with at least 1 dose of venetoclax at 800 mg showed antileukemic activity in addition to the ORR. The median duration of CR was 48 days. Of those who received a prior hypomethylating agent (n = 24), the ORR was 25%, which consisted entirely of CR/CRi. In those with IDH mutations (n = 12), the CR/CRi rate was 33%, which was split evenly between CRs (17%) and CRis (17%). The 6-month overall survival (OS) rate was 36% (95% CI, 20-53) and the median OS was 4.7 months.
The leukemia-free survival (LFS) rate at 6 months was 10% and the median LFS was 2.3 months. This new data adds to findings for venetoclax in combination with a hypomethylating agent for AML. In January 2016, venetoclax received an FDA breakthrough therapy designation for use in combination with hypomethylating agents in treatment-naïve patients with AML who are not eligible for standard high-dose induction treatment.
Early Stop Not in Store for Phase III Abemaciclib Study
The phase III MONARCH 2 study assessing abemaciclib in HR-positive, HER2-negative advanced breast cancer will continue after the CDK4/6 inhibitor did not meet the efficacy criteria at an interim analysis required to stop the trial early. The international, double-blind phase III MONARCH 2 trial randomized 669 patients in a 2:1 ratio to abemaciclib plus fulvestrant or fulvestrant alone. Patients had progressed during or within 1 year of receiving endocrine therapy in the neoadjuvant or adjuvant setting, or during frontline endocrine treatment for metastatic disease.
Individuals were excluded from enrollment if they were administered chemotherapy in the metastatic setting. The primary endpoint for the trial is progression-free survival. MONARCH 2 follows the phase II MONARCH 1 trial, in which abemaciclib induced a response rate of nearly 20% in heavily pretreated patients with refractory HR—positive, HER2-negative advanced breast cancer. In the single-arm phase II study, the median PFS was 6 months and the median overall survival was 17.7 months. Abemaciclib previously received a breakthrough therapy designation in this setting from the FDA in October 2015.
Selumetinib Fails to Improve Survival in Lung Cancer Study
The combination of selumetinib and docetaxel failed to improve survival compared with docetaxel alone as a second-line treatment for patients with KRAS-mutant locally advanced or metastatic non—small cell lung cancer, according to top-line findings from the phase III SELECT-1 trial. In the phase III study, 510 patients with KRAS-mutant NSCLC were randomized to receive docetaxel plus placebo or selumetinib.
A meaningful difference was not observed between the two groups for progression-free survival and overall survival. Adverse events associated with the combination were inline with expectations. Full results from the trial will be presented at an upcoming medical meeting, according to the company. The combination of selumetinib and docetaxel had shown promising results in a prior phase II study, which raised expectations for the phase III study. In July 2015, selumetinib also failed to improve PFS when added to dacarbazine for patients with metastatic uveal melanoma in the phase III SUMIT trial. Prior to this development, the agent had similarly shown promising phase II results.