It takes an average of 12 years to move a drug from a new application to approval for a specific indication. Twelve years of clinical trials, documentation of several endpoints, and data surrounding incidence of observed adverse events and expected severity. Twelve years until a broader subset of patients can access the drug.

To address the challenges in drug availability and critical need for treatment options, the U.S. Food and Drug Administration (FDA) allows for some instances of expedited approval. Fast-track approval is one such option and can drastically facilitate drug development and expedite the review process, potentially reducing the amount of time an agent remains in clinical trials by several years.

Agents that treat a serious condition or fill an unmet need are eligible for fast-track approval. Other justifications for fast-track approval when treatment options already exist include suggesting superior clinical efficacy and avoiding or decreasing toxicity of serious side effects associated with existing approved treatment options.

Fast-track approval can be granted in the event that a well-designed clinical trial demonstrates efficacy on a single surrogate endpoint that may suggest long-term clinical effectiveness. Once approved, FDA requires the industry to continue post-marketing studies to continue to examine long-term clinical efficacy.

During a recent five-year period, 30% of agents approved through the fast-track process were anticancer agents used in either the treatment or precancerous phases. But the longer an agent spends in clinical trials and in the FDA approval process, the more adverse events are reported.

Recognize It; Report It

Because of that significant gap, FDA encourages healthcare clinicians to continue to report adverse events and toxicities through its MedWatch Program as a means of collecting safety data in the postmarketing phases of drug use. ONS recently launched the “Recognize It; Report It” campaign to raise awareness among nurses about their role in reporting observed side effects and toxicities when patients are receiving drugs that achieved a fast-track approval. ONS encourages reporting observed adverse events, regardless of anticipated relatedness to the agent, as a means of contributing to a comprehensive repository of drug-specific data and timely communication for adverse events.

Advanced practice RNs (APRNs) are often the first touch point for patients undergoing cancer treatment. APRNs assess patients returning to the clinic for evaluations between and at the start of each new cycle and collect information to contribute to the decisions about fitness for continued therapy or the need to hold therapy based on toxicity profile.

In the event a drug received fast-track approval, APRNs have limited information about the likelihood of a specific toxicity, thus impacting the way they make decisions as part of the care team. Recognize It; Report It encourages reporting observed side effects and grading not only to the cancer care team involved in the care of one specific patient but also to FDA to potentially impact the way APRNs across the country are approaching patient care and decision making.

Implications for APRN Practice

Failing to report observed adverse events because they are thought to be unrelated or insignificant could delay attributing the event to the agent. Should a toxicity not be reported because it is already documented, its incidence may be misrepresented or underestimated.

Creating a nationwide comprehensive database of observed toxicities and their severity is critical to contributing to healthcare clinicians’ understanding of a drug in the post-market arena. APRNs are essential to the development and major benefactors of a database leading to the full understanding of acute and long-terms adverse events associated with fast-track agents in cancer care. Furthermore, APRNs are critical to advocating that their organization as whole commit to reporting observed side effects while patients are on therapy, regardless of suspected causal relationship.

CASE STUDY

C.S. is a 67-year-old woman newly diagnosed with left breast mass. She has a history of hypertension, for which she takes lisinopril, and hypercholesterolemia managed with lovastatin for many years. She had a biopsy that showed invasive ductal carcinoma, estrogen receptor 99%, progesterone receptor 96%, HER2 negative, and Ki-67 72%. At the time of diagnosis, she was also complaining of increased back pain. A positron-emission tomography scan showed a lesion at T6, and a biopsy confirmed breast cancer. No other metastatic disease was found. Baseline complete blood counts (CBC) and comprehensive metabolic panels (CMP) were normal. CA 27.29 was elevated to 53 U/mL (normal < 39 U/mL).

She was started on anastrazole and eventually palbociclib. C.S. was also referred to radiation therapy for local pain control of T6. Two weeks after starting both medications, her CBC showed grade 2 neutropenia with normal CMP. At one month, her liver function tests (LFTs) were elevated, with ALT 184 IU/L (normal 6–29 IU/L) and AST 84 (normal 10–35 U/L). At two months on therapy her liver function tests were ALT 619 IU/L and AST was 750 IU/L. The care team decided to hold both medications. It took one month for her liver function test to show ALT 252 IU/L and AST 78 U/L.

Her LFTs were considered a grade 4 per the Common Terminology Criteria for Adverse Events. The medication was help. Her LFTs did eventually decrease to a grade 2, which allows restarting her palbociclib at a lower dose. See ONS’s targeted therapy resources for more information about managing adverse events.

Although liver enzyme elevation is a well-documented adverse event associated with palbociclib, grade 4 events are reported to occur in less than 1% of cases. The care team decided it was appropriate to initiate an alert to the FDA about this toxicity to ensure the toxicity’s incidence and severity were estimated correctly.

Practice filling out the MedWatch form at the FDA’s website.

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