The US FDA has issued guidelines for clinical trials related to the approval of non-small cell lung (NSCL) drugs and biologics. The purpose of the guidance is to evaluate drugs to treat lung cancer.

The regulatory authority has clearly stated that for regular approval of a new drug applications (NDA) and biologics license applications (BLA), the applicant must show direct evidence of clinical benefit. It has now quickened the approval pathway for approval of drugs or biological products that are intended to treat serious or life-threatening diseases like the non-small cell lung and that provide a meaningful therapeutic benefit over existing treatments.

The American Cancer Society estimated that there would be nearly 2,28,190 new cases of lung cancer. In fact, lung cancer accounts for approximately 14 per cent of all new cancers and it is the leading cause of fatality, accounting for about 27 per cent of all cancer deaths. Evaluation of new drugs for the treatment of lung cancer is based on well-conducted and controlled trials to assess and establish clinical benefit of the therapy.

According to Kidwai Institute of Oncology, Bengaluru which is largest government run cancer care in Karnataka, the need for a guidance was found wanting because it was critical to bring in clarity on the treatment options.

The regulator has said that specifically, speedy approvals may be based on a clinical benefit; or can be measured in terms of being able to reverse morbidity. In the past, three commonly used efficacy in trials assessing treatments of lung cancer were overall survival (OS), time to progression (TTP) or progression-free survival (PFS), and objective tumour response rates (ORR).

Reduction in patients’ of tumour-related symptoms have also been used as an efficacy endpoint. The majority of drug approvals for non-small cell lung have been based on a significant improvement in overall survival, as the median survival was relatively short which is less than a year.

In addition, overall survival is an optimal endpoint because the measurement is accurate, is observed on a daily basis. It provides direct evidence of clinical benefit to the patient. Regular approval was granted on the basis of a significant improvement in overall survival. Similarly, reduction in patients’ tumour-related symptoms can also provide direct evidence of clinical benefit and can support regular approval.

The criteria for disease progression and tumour response are based on subjective interpretation of radiographic images and clinical evaluation. These subjective interpretations have potential to introduce bias, particularly when evaluated in open-label trials.

Specifically, primary lung tumours and regional nodal disease frequently have ill-defined borders that can be difficult to accurately measure radiographically. Therefore, confidence in tumour measurement-based outcomes depends on the frequency of assessments as well as clear, objective criteria for defining disease progression and tumour response, said the regulatory authority.