The Accelerated Approval of Oncologic Drugs

Myocardial Protection During Cardiotoxic Chemotherapy

“…These events increased to 48% at 2.7 years, occurred even in young patients and in patients without coronary risk factors, and prompted the US Food and Drug Administration to restrict the indication of this drug to patients with T315I mutations or in those for whom all other TKIs have failed. 22 Cisplatin can activate the arachidonic acid pathway in platelets, enhance thromboxane formation, and induce platelet aggregation, and it has been found to cause arterial and venous thromboembolism in up to 18% of patients. 23 Angiogenesis inhibitors are also associated with a high risk of venous thromboembolism 24 ( Table 1).…”

“…As learned from the cardiotoxic effects of secondgeneration TKIs, 21,22 cardiology and oncology scientific societies should work together with regulatory agencies to establish uniform criteria to precisely define chemotherapyinduced cardiac toxicity, the methods to monitor the cardiovascular safety of novel cancer therapies, and a precise protocol to evaluate cardiovascular events in all randomized, controlled studies. Finally, oncologists and cardiologists should work together to develop clear clinical guidelines for the prevention and management of chemotherapy-induced cardiotoxicity.…”

The hazards of rapid approval of new drugs

“…8 Ponatinib was subsequently removed from the market because nearly half the patients had adverse vascular effects, such as venous thromboembolism, at three years. 1 With more data at an earlier stage ponatinib may never have ever been approved. It has now been marketed in Australia with a black box warning about its potentially fatal adverse effects.…”

“…However, approval can be made too early for drugs with limited data or data reliant on biochemical surrogate markers. 1 There is less chance of identifying adverse drug reactions before marketing for drugs that undergo fast-track approval. 2 Canada has also developed a fast-track process and a recent analysis found that safety warnings are significantly more likely after this process than they are with drugs approved through the usual regulatory process.…”

Risks and Benefits of Phase 1 Clinical Trial Participation

“…34 However, the correlation between the risk of thrombotic events was made only after ponatinib had been approved by the FDA for the treatment of chronic myelogenous leukemia blast crisis or those with a T315I mutation. 35 With regard to patient satisfaction, many patients do not feel better about their disease once their trial participation is completed. 32 With the advent of biomarker-driven trials that require the testing of tumor tissue, the unavailability of tissue for future trials can become an issue.…”