Does the oncology community have a rejection bias when it comes to repurposed drugs?

Abstract

Among the various measures proposed to combat the challenge of financial toxicity in cancer care, an important strategy is the use of lower-priced drugs instead of expensive alternatives. However, the oncology community seems to either ignore or more readily reject cheaper drugs in cancer care compared to more expensive alternatives. In this commentary, we present three examples of lower-priced drugs rejected or ignored by the oncology community and contrast this with three expensive drugs where persistent optimism remained despite negative clinical trial results. We argue that all drugs be held to the same rigorous standards – this not only includes skepticism in the absence of sound evidence, but also the suspension of premature judgement as has happened in the cases of repurposed drugs.

A phase 2 trial of neoadjuvant metformin in combination with trastuzumab and chemotherapy in women with early HER2-positive breast cancer: the METTEN study

“…Consequently, ethical issues arose during the METTEN study trial based on the recommended standard of care supported by national and international guidelines with a neoadjuvant combination of taxane-containing chemotherapy and a dual blockade of trastuzumab and pertuzumab. Moreover, we cannot exclude the possibility that a rejection bias might exist against the repurposing of generic non-cancer metformin as oncological treatment when confronted to commercially developed anti-cancer drugs [ 65 ].…”

Repurposing old drugs in oncology: Opportunities with clinical and regulatory challenges ahead

“…This may be due to the possibility that pancreatic cancer patients lack a hyperinsulinaemic state. Gyawali et al have provided a critical review of this study, arguing lack of study power, imbalance between the two groups and other confounding factors. A study by Zhao et al also randomly assigned 60 postmenopausal women with hormone receptor positive locally advanced or metastatic breast cancer to aromatase inhibitor plus metformin or placebo.…”

“…This may be due to the possibility that pancreatic cancer patients lack a hyperinsulinaemic state. Gyawali et al 71 international prospective clinical trials indicates that metformin has the potential to improve clinical outcomes. 63 In contrast, a prospective Phase Ib study in nine patients with other (nonrenal) advanced cancers reported that a combination of everolimus and metformin was poorly tolerated.…”

“…Given that the effect and the risk/benefit of an old drug depend on its pharmacokinetics, on target and off‐target potencies and tissue concentrations, caution must be exercised in dismissing other members of its class if one particular member is found to be ineffective. For example, Gyawali et al have argued for investigating simvastatin (although pravastatin failed) in improving the outcomes in patients with small cell lung cancer treated with chemotherapy . These two statins differ markedly in their hydrophobicity; simvastatin being hydrophobic and pravastatin being hydrophilic.…”

Metformin in Oncology – How Far Is Its Repurposing as an Anticancer Drug?

“…For example, in a placebo-controlled phase II randomized clinical trial, metformin did not improve outcomes in patients with advanced pancreatic cancer [38]. However, this trial is quite controversial [39] since patients receiving metformin had more advanced disease (based on values of marker CA19.9), and they also received fewer treatment cycles. Results of another phase II trial in patients with advanced pancreatic cancer receiving standard systemic therapy with or without metformin (2 g daily) were reported [40] with no significant difference in 6-months progression-free, disease-free and overall survival between groups.…”