Top news of the week in oncology and cancer drug development.
FDA Eliminates REMS Requirement for ESAs
The FDA has eliminated the need for risk evaluation and mitigation strategy (REMS) certification prior to the administration of erythropoiesis-stimulating agents (ESAs) for anemia due to myelosuppressive chemotherapy. The decision applied specifically to the agents epoetin alfa (Epogen/Procrit) and darbepoetin alfa (Aranesp).
"The FDA has released the REMS requirements for the ESA products, Epogen/Procrit and Aranesp, and the risks can be communicated by the current product prescribing information," the agency noted. "The appropriate use of ESAs is supported by the CMS National Coverage Determination, the American Society of Clinical Oncology and American Society of Hematology clinical guidelines, which are evidence-based guidelines intended to provide a basis for the standard of care in clinical oncology."
In the clinical studies leading to the approvals for the ESAs it was determined that treatment with the agents led to a shorter overall survival and/or increased risk of progression or recurrence in patients with breast cancer, non—small cell lung cancer, head and neck cancer, lymphoid cancer, and cervical cancers. Additionally, in chronic kidney disease trials, patients with a hemoglobin level greater than 11 g/dl treated with ESAs were more likely to die or have a serious cardiovascular adverse event or stroke.
Amgen, the company marketing darbepoetin alfa, submitted the data for removal of the REMS. The data that led to the decision were from surveys showing that prescribers were aware of the risks associated with ESAs and that the agents were being used appropriately and according to the approved indication.
FDA Approval Sought for Denosumab in Myeloma
A supplemental biologics license application (sBLA) has been submitted to the FDA for the use of denosumab (Xgeva) for the prevention of skeletal-related events (SREs) in patients with multiple myeloma, according to Amgen, the developer of the RANK ligand inhibitor. The sBLA is based on data from the phase III 482 study, which were presented at the 16th International Myeloma Workshop in New Delhi.
In the trial, denosumab demonstrated noninferiority to zoledronic acid (Zometa) at delaying the time to the first skeletal-related event (SRE) in patients with multiple myeloma (HR, 0.98; 95% CI, 0.85-1.14; P = .01). The median time to first on-study SRE was similar between the treatments, at 22.83 months with denosumab versus 23.98 months with the bisphosphonate zoledronic acid. The median progression-free survival was 10.7 month higher in the denosumab arm (HR, 0.82; 95% CI, 0.68-0.99; P = .036).
There was also a nonstatistically significant trend in overall survival (OS) favoring denosumab (HR, 0.90; 95% CI, 0.70-1.16; P = .41). Adverse events (AEs) in the study were consistent with the known safety profile for denosumab. The most common AEs in the denosumab arm were diarrhea (33.5% vs 32.4% with zoledronic acid) and nausea (31.5% vs 30.4%).
Alectinib Beats Crizotinib in Frontline ALK+ NSCLC ALEX Trial
Alectinib (Alecensa) reduced the risk of disease progression or death compared with crizotinib (Xalkori) as a frontline treatment for patients with ALK-positive non—small cell lung cancer (NSCLC), according to findings from the phase III ALEX trial. The much-anticipated ALEX findings are the confirmatory data for the December 2015 FDA accelerated approval of alectinib as a treatment for patients with metastatic ALK-positive NSCLC following progression on crizotinib.
Genentech (Roche), the developer of the second-generation ALK inhibitor alectinib, plans to present the ALEX results at an upcoming medical meeting and submit the data to the FDA and other global regulatory agencies. ALEX is now the second phase III trial in which alectinib has bested crizotinib in frontline ALK-positive NSCLC. Alectinib improved progression-free survival (PFS) by 66% versus crizotinib in the Japanese open-label phase III J-ALEX study, which was presented at the 2016 ASCO Annual Meeting.
Alectinib previously received an FDA breakthrough therapy designation as a frontline treatment for patients with ALK-positive NSCLC. The open-label phase III ALEX study (NCT02075840) randomized 303 treatment-naive patients with ALK-positive NSCLC in a 1:1 ratio to alectinib or crizotinib. PFS was the primary endpoint of the study, which was conducted at 161 locations across 31 countries. According to Genentech, adverse event data in ALEX were similar to previous alectinib trials, with no new safety signals.
USPSTF Could Drop Its Opposition to Routine Prostate Cancer Screening
The US Preventive Services Task Force (USPSTF) may move away from its long-standing opposition to routine PSA screening for prostate cancer in some men. In a draft guideline released today, the task force takes the position that for men aged 55 to 69, the decision to undergo screening “is an individual one.” The task force said physicians should inform their patients of the risks and benefits associated with screening, and they should decide on the best course of action together.
“Screening offers a small potential benefit of reducing the chance of dying of prostate cancer. However, many men will experience potential harms of screening, including false-positive results that require additional workup, overdiagnosis and overtreatment, and treatment complications such as incontinence and impotence,” the task force said in its recommendation. “The USPSTF recommends individualized decision-making about screening for prostate cancer after discussion with a clinician, so that each man has an opportunity to understand the potential benefits and harms of screening and to incorporate his values and preferences into his decision.”
The draft recommendation also applies to adult men who have not been previously diagnosed with prostate cancer and have no signs or symptoms of the disease, men at average risk, and men who are at increased risk for prostate cancer, including African-American men and men with a family history of prostate cancer. USPSTF still recommends against screening for men aged 70 and older. The guideline is not final and remains open for public comment until May 8.
COA Slams MedPAC's Drug Cost Containment Plan
A set of draft recommendations for controlling price escalation in the Medicare Part B program has ignited fresh concern from the oncology community, which battled last year to overcome the Medicare Part B Drug Payment Model cost reduction experiment. Part B covers injectable and infusion drugs. The proposed changes from the Medicare Payment Advisory Commission (MedPAC) are designed to achieve savings by incentivizing physicians to opt for negotiated price reductions on the drugs they prescribe. However, some in the oncology community are fearful their revenues will shrink even further than they have in recent years as a result of federal budget cuts and the 340B Drug Discount Program.
“The data clearly show that reducing Part B payments has had disastrous unintended consequences on the US cancer care system,” the Community Oncology Alliance said in a release. “Past cuts have only fueled a dramatic shift in the site of cancer care delivery into the far more expensive hospital outpatient setting.”
The MedPAC late last week decided to recommend that Congress adopt the payment policy revisions. The draft modifications would move physicians away from the current, predominant system of payment, under which physicians are paid the average sales price (ASP) of drugs plus a 6% markup to cover administration and other expenses. Instead, physicians would purchase drugs from a formulary whose prices have been negotiated by third-party vendors. Medicare does not have the authority to negotiate drug prices itself, and this system would skirt that obstacle, which has been blamed for Medicare’s current difficulty in bringing down the cost of medicine.