Comparison of Drugs in the Metastatic and Adjuvant Settings

A study published in JAMA Network Open found that in non-small cell lung cancer (NSCLC), breast cancer, and colon cancer, only 34.8% of drugs endorsed in the metastatic setting are also endorsed in the adjuvant setting. 

Given the potential benefit of adjuvant therapy in these disease spaces, the researchers indicated that further investigation into additional adjuvant systemic therapy options is necessary. 

“This finding is likely associated with a multitude of factors, especially the higher burden of proof required for adjuvant therapies and a general lack of correlation between efficacy of a drug in advanced cancers and benefit in early disease,” the authors wrote. “Although there are a number of ongoing trials aimed at elucidating additional agents for adjuvant use, there is still a high percentage of drugs that have yet to be studied, suggesting possible future directions.”

In this cross-sectional study, researchers used National Comprehensive Cancer Network (NCCN) treatment guidelines current as of May 15, 2019 and included clinical trials that cited either these guidelines or trials that were within corresponding drug labels. Trials that were published between 1970 and 2019 were assessed, and the analysis included published clinical trials of systemic therapy options deemed by the NCCN as category 1 or 2A. 

The participants included in clinical trials evaluating current NCCN-recommended systemic therapy options were patients with early or metastatic NSCLC, breast cancer, or colon cancer. Overall, the study identified 69 agents recommended for use in metastatic disease compared with 25 agents recommended for adjuvant use. 

For therapies used in both settings, the mean (SD) delay between use in metastatic disease and as an adjuvant therapy was found to be 10.0 (7.5) years. Moreover, with consideration to trials with positive outcomes, 39 of 69 agents (56.5%) were either approved or recommended in the metastatic setting, compared to 23 of 25 agents (92.0%) that were approved for use as an adjuvant therapy.

“Given the higher stakes of adjuvant therapy, this difference is logical: as opposed to the largely noncurative intent for most metastatic cancer treatments, adjuvant treatment is aimed at increasing the fraction of patients cured of their disease,” the authors wrote. “It follows then, that there exists a higher burden of proof for adjuvant therapies.”

Ultimately, the researchers indicated that it is unclear whether the delay between adoption of a therapy in metastatic cancers and as an adjuvant treatment has changed over the last 5 decades. However, the researchers highlighted that of the 31 new agents approved or recommended for use in metastatic NSCLC, breast cancer, or colon cancer since 2010, only 2 have been approved for adjuvant use, at a delay of 5.50 and 6.25 years, respectively. 

“It should be noted that despite the fact that most of the agents used in metastatic disease have been evaluated in the adjuvant setting, there are still approximately 20% of these agents that have yet to be studied for this purpose,” the authors wrote. “The reasons for this are likely numerous and full consideration is beyond the scope of this discussion; however, this number suggests that there is still room for further exploration among existing agents.”

Importantly, there have been a number of immunotherapy or targeted therapy agents in cancer types not detailed in the study that the researchers suggested have demonstrated a quicker transition between the metastatic and adjuvant treatment settings. It remains to be seen though whether this pace is indicative of an acceleration in drug development.

Reference:

Parsons S, Maldonado EB, Prasad V. Comparison of Drugs Used for Adjuvant and Metastatic Therapy of Colon, Breast and Non-Small Cell Lung Cancers. JAMA Network Open. doi:10.1001/jamanetworkopen.2020.2488.