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Higher response rates the most compelling driver The obvious clinical driver for the development of CDx is to direct appropriate therapies to those patients most likely to respond ( Figure 18 ).
Figure 18 : Drivers for the use of CDx
Clinical
Economic
Scientific
Other
• High need to identify likely responders
• Need to identify patients more likely to experience side effects
• Identification and subsequent treatment of patients likely to respond reduces unnecessary therapy costs and increases chances of clinical trial success .
• Regular monitoring allows termination of treatment when patients no longer benefit
• A high number of targeted therapies and immunotherapies are already approved , some in combination with biomarkers
• First liquid biopsy test for cancer gained FDA approval in June 2016 ( cobas EGFR , Roche ), paving the way for additional approvals
• Cancers are highly complex , and biomarkers need to determine the best course of treatment
• Targeted therapies are considerably more efficacious in relevant in patients expressing relevant biomarkers
Source : goetzpartners Research
Analysis of the targeted drugs approved over the last 15 years reveals that the ORR for drugs with CDx ranged from 41 % - 80 % compared to 7 % - 45 % for those where no CDx is available ( Table 12 ). This equates to a more than doubling of the median ORR to 55 % from 23 %.
Screening patients CDx can more than double median response rates
Table 12 : Responses to targeted therapies with and without CDx |
Drug |
Indication |
Biomarker ( s ) |
Response rate (%) |
DRUGS WITH CDX Pertuzumab ( Perjeta ) |
Breast cancer |
HER2 |
80.2 |
Crizotinib ( Xalkori ) |
NSCLC |
ALK |
65.0 |
Erlotinib ( Tarceva ) |
NSCLC |
EGFR |
65.0 |
Osimertinib ( Tagrisso ) |
NSCLC |
EGFR T790M |
59.0 |
Cetuximab ( Erbitux ) |
Colorectal cancer |
EGFR / KRAS |
57.0 |
Imatinib mesylate ( Gleevec ) |
GIST |
CD117 |
53.9 |
Dabrafenib ( Tafinlar ) |
Melanoma |
BRAF |
52.0 |
Vemurafenib ( Zelboraf ) |
Melanoma |
BRAF |
48.4 |
Ado-trastuzumab emtansine ( Kadcyla ) |
Breast cancer |
HER2 |
43.6 |
Pembrolizumab ( Keytruda ) |
NSCLC |
PD-L1 |
41.0 |
DRUGS WITHOUT CDX Bevacizumab ( Avastin ) |
Colorectal cancer |
− |
45.0 |
Ixabepilone ( Ixempra ) |
Breast cancer |
− |
34.7 |
Paclitaxel protein-bound particles ( Abraxane ) |
NSCLC |
− |
33.0 |
Pemetrexed ( Alimta ) |
NSCLC |
− |
27.1 |
Pembrolizumab ( Keytruda ) |
Melanoma |
− |
24.0 |
Capecitabine ( Xeloda ) |
Colorectal cancer |
− |
21.0 |
Ziv-aflibercept ( Zaltrap ) |
Colorectal cancer |
− |
19.8 |
Eribulin Mesylate ( Halaven ) |
Breast cancer |
− |
11.0 |
Ipilimumab ( Yervoy ) |
Melanoma |
− |
10.9 |
Sunitinib malate ( Sutent ) |
GIST |
− |
6.8 |
The indications in the table are for advanced and / or metastatic disease . All drugs listed obtained FDA approval after 2000 . Abbreviations : GIST , gastrointestinal stromal tumours ; NSCLC , non-small cell lung cancer Source : ( Jorgensen & Hersom , 2016 )
The use of CDx should not only maximise survival benefits , but also facilitate patient selection allowing for smaller , more targeted pivotal clinical trials as well as easing the drug ’ s course through the regulatory process . Many of the recent approved CDx have been approved in trials consisting of < 200 eligible patients and the FDA has received criticism for not properly evaluating the risk / benefit profile . There is also a significant need for markers to monitor disease after treatment to allow for rapid intervention before the returning cancer becomes symptomatic or visible by imaging . Equally , monitoring helps to identify any change in drug susceptibility ( e . g ., driver mutation profile ) so that the drug regime can be
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