Top news of the week in oncology and cancer drug development.
Full Approval Sought for Blinatumomab in Acute Lymphoblastic Leukemia
A supplemental biologics license application (sBLA) has been submitted to the FDA for the full regulatory approval of blinatumomab (Blincyto) as a treatment for patients with Philadelphia chromosome-negative (Ph-) relapsed/refractory B-precursor acute lymphoblastic leukemia (ALL), according to the developer of the anti-CD19 immunotherapy, Amgen.
The sBLA was based on data from the phase III TOWER study, in which the median overall survival (OS) with blinatumomab was 7.7 months versus 4 months with standard chemotherapy. The application also provides data supporting the use of blinatumomab in patients with Philadelphia chromosome-positive (Ph+) relapsed/refractory B-cell precursor ALL. In the TOWER trial, treatment with blinatumomab reduced the risk of death by 29% versus standard chemotherapy (HR, 0.71; 95% CI, 0.55-0.93; P = .012).
The OS benefit with blinatumomab was observed across prespecified patient subgroups based on age, prior salvage therapy, or alloSCT. The study was halted early for efficacy based on the recommendation of an independent data monitoring committee. The CR rate with blinatumomab was 39% versus 19% with standard chemotherapy (P <.001). The combined CR/CRh/CRi rates were 46% versus 28%, respectively (P = .001). The FDA granted an accelerated approval to blinatumomab in 2014 as a treatment for patients with Ph- relapsed/refractory B-precursor ALL, based on findings from a phase II trial. According to Amgen, Blincyto’s label includes a Boxed Warning regarding cytokine release syndrome and neurological toxicities.
Antibiotics May Damper Efficacy of Checkpoint Inhibitors
Use of antibiotics up to a month before treatment with a checkpoint inhibitor may decrease the efficacy of the immunotherapy agent, results of a retrospective analysis show. The analysis, presented during a presscast ahead of the 2017 Genitourinary Cancers Symposium, raised suspicion of the relationship between gut microbiota and antibiotics and their effect on immune checkpoint blockade agents.
In patients with metastatic renal cell carcinoma, patients who had received broad-spectrum antibiotics had a shorter median progression-free survival (PFS) rate when treated with checkpoint inhibitor immunotherapy than those who had not received antibiotics of 2.3 versus 8.1 months, respectively (P <.001). At a median follow-up of 6 months, overall survival (OS) results were not yet able in the overall population, but a negative trend was already noted for patients who received prior antibiotics.
The objective response rate also favored patients who had not received antibiotics (P <.002). In a subgroup of 62 patients who were treated with nivolumab (Opdivo) monotherapy, patients who had not taken antibiotics showed a greater PFS rate, which also achieved statistical significance (P <.009). OS in the nivolumab monotherapy subgroup was also significantly higher in patients who had not taken recent antibiotics (P <.003). A multivariate analysis for prognostic risk factors showed a hazard ratio of 4.17 (95% CI, 1.92-9.08) for patients who had not received antibiotics compared with those who had taken antibiotics (P <.001).
Patients Who Discontinue Immunotherapy Early May Still Benefit From Treatment
Some patients who had to stop their PD-1/PD-L1 immunotherapy because of an immune-related adverse event (irAE) proved to be sustained responders, even after being off the therapy for more than 6 months, according to newly reported findings from a small study of patients receiving checkpoint inhibitors for metastatic renal cell carcinoma (mRCC). In this retrospective analysis involving 19 patients, 8 (42%) were able to remain off additional systemic therapy for more than 6 months, and of these, 6 patients continue to be free from progression, as reported during a presscast in advance of the 2017 Genitourinary Cancer Symposium.
The analysis is based on patients with mRCC who received treatment at 1 of 5 academic centers but had ceased PD-1/PD-L1 inhibitor therapy due to an irAE. Reasons for stopping therapy included joint pain, eye problems, diarrhea, and organ inflammation. Most of the patients (63%) had received their PD-1/PD-L1 treatment as monotherapy, and the remainder had their immunotherapy in combination with other systemic treatments. In addition to the 8 durable responders, 3 patients were deemed “immediate progressors,” that is, they required additional treatment less than 4 months after discontinuing their PD-1/PD-L1 therapy; the 8 other patients stopped responding 4 to 6 months after discontinuing treatment.
Circulating Tumor DNA Can Advance Personalized Care in mCRPC
Up to 94% of patients with metastatic castration-resistant prostate cancer (mCRPC) have circulating tumor DNA (ctDNA) with at least 1 genetic alteration, suggesting ctDNA could be a noninvasive alternative to traditional tumor biopsies and help personalize treatment in this setting. The research, which was presented during a presscast held ahead of the 2017 Genitourinary Cancers Symposium, showed that a ctDNA assay identified potentially actionable molecular alterations in patients’ tumors.
Further, higher overall numbers of genetic alterations, including changes in the androgen receptor (AR) gene, were associated with poorer treatment outcomes. The researchers assessed cell-free ctDNA from blood samples of 514 patients with mCRPC who received baseline ctDNA analysis for potentially actionable alterations using the Guardant360 assay, a 70-gene ctDNA next generation sequencing panel. The assay provides complete exon sequencing for 29 genes, critical exons in 39 genes, and amplifications (16 genes), fusions (6 genes) and indels (3 genes) harvested from 10 mL of peripheral blood. Of the 514 patients, 94% (482) had at least 1 ctDNA alteration.
The median age of these patients was 70 years (range, 39-91). The most frequently detected recurrent somatic mutations included TP53 (36% of patients), AR (22%), APC (10%), NF1 (9%), EGFR, CTNNB1, and ARID1A (6% each), and BRCA1, BRCA2, and PIK3CA (5% each). Additionally, the most common genes with increased copy numbers were AR (30%), MYC (20%), and BRAF (18%). Clinical results were available for 163 patients, of whom 28.8% (46) were treatment-naive. There was an association between higher levels of ctDNA alterations and shorter time to failure (TTF; HR, 1.05; P = .026). With AR alterations specifically, there were trends toward short TTF (HR, 1.42; P = .053) and survival (HR, 2.51; P = .09). Further, the rates of new alterations in AR were higher in previously treated patients versus treatment-naive patients at 56% versus 37%, respectively (P = .028).
Tom Price Confirmed as HHS Secretary, Will Lead ACA Repeal
The Senate voted to confirm US Rep. Tom Price, R-Georgia, as secretary of HHS. President Donald Trump nominated Price with the expectation that he will lead the charge to repeal and replace the Affordable Care Act. In a statement on the confirmation, the American Society of Clinical Oncology wrote, “ASCO looks forward to working with Secretary Price to sustain national investments in cancer research and patient access to high-quality cancer care. We are hopeful that his appointment will positively impact the care received by all Americans with cancer.”