Written by Sharmin Begum, science writer
Next-Generation Sequencing (NGS) strategies were compared in patients with metastatic non-small cell lung cancer (NSCLC) in Hong Kong. The results were analysed to determine the clinical and economic impact of NGS and targeted therapy.
In a study published by Elsevier, researchers developed an economical model to compare the efficiency of various NGS tests for patients with metastatic NSCLC (mNSCLC). In East Asia, the treatment received by NSCLC patients can be limited and is potentially impacted by the varying rates of molecular testing employed across the region. In comparison, in countries such as the USA – where actionable mutations and the cost of healthcare can be more favourable – upfront NGS in patients with NSCLS has been associated with quicker and cheaper results.
This study looked at sequential, panel, exclusionary and up-front NGS testing of genomic alterations (GAs) in mNSCLC patients. The study aimed to analyse the best testing option in terms of cost, time-to results and actionable versus non-actionable GA detection rate.
“There remains a considerable need to improve the implementation of efficient and cost-saving molecular testing strategies in East Asian clinical practice to meet guideline recommendations and ultimately improve patient survival”, says Herbert H. Loong, lead author of the study.
Importance of molecular testing
NSCLC is the most common form of lung cancer, with 46% of worldwide deaths from lung cancer occurring in East Asia. Improvements in treatment and survival rates have been influenced by the development and implementation of therapies targeted against genomic alterations (GA) in driver oncogenes, which have been identified in NSCLC.
Determining an optimal molecular testing strategy is of great value; in particular, (1) whilst there is a rise in identifying other potential actionable oncogene targets, and (2) in addition to ongoing clinical trials in targeted therapies for NSCLC driver oncogene alterations. The significance of molecular testing and identifying GAs is reflected in how standard of care therapies are already evolving from chemotherapy to personalised therapy.
Decision analytical model
Using Microsoft Excel, researchers developed an analytical model to evaluate upfront NGS testing and three other modalities of molecular testing, including exclusionary, single-gene sequential, and hotspot panel testing. The testing population consisted of 4,094 adult patients in Hong Kong, newly diagnosed with mNSCLC in a given year, collated from the 2016 Hong Kong Census. With reference to the current Hong Kong market, the study aimed to estimate the differences in molecular testing costs, time to appropriate therapy and the proportion of patients with actionable or non-actionable genomic alterations.
GA’s were categorised into either actionable or non-actionable- depending on the availability of Hong Kong approved treatments. Initially, the most prevalent alterations were identified by simultaneous testing of epidermal growth factor receptor (EGFR) mutations and anaplastic lymphoma kinase (ALK) translocations in sequential or exclusionary testing. Subsequently, patients with a negative result would continue testing for the next actionable alteration using the sequential gene-testing modality of NGS, depending on available tissue sample. Hotspot testing would include all actionable GAs, in comparison to upfront NGS testing which included all potential NSCLC GAs in one test.
Clinical and economic impact
The study revealed that compared to the three other modalities of molecular testing, exclusionary testing (single-gene testing for EGFR and ALK, followed by NGS) in mNSCLC patients resulted in lower costs ($3.9-$7.5 million cost savings) and shorter time to therapy (1.6 weeks). These findings are in stark contrast to previous findings by Pennell, who found that the most cost saving strategy in the USA was upfront NGS, potentially due to disparities in mutation epidemiology between Western and East Asian populations.
Nevertheless, researchers predict that upfront NGS testing could become the cheaper option if the unit cost of NGS was reduced, together with a rise on more actionable GAs. Researchers noted that whilst the three other modalities of molecular testing are cheaper in comparison to upfront NGS, not all alterations are identified, which has a direct impact on patients receiving optimal treatment options. Researchers established that upfront NGS enabled the identification of not only 100% of patients with actionable GAs, but also 61.3% of patients with non-actionable GAs, who were eligible for clinical trial enrolment with novel treatments.
Whilst the model developed in this study was based on the Hong Kong market, researchers say that it can also be used to represent mNSCLC patients throughout East Asia, due to similarities in driver mutation epidemiology. The researchers acknowledge that the focus of the study was restricted to genomic testing-related costs and didn’t consider variables such as costs of treatment, monitoring and adverse event-related costs.
This study model has established that the current approach of sequential testing strategies can be improved, in terms of clinical benefit and economic savings, by employing an exclusionary testing strategy. The model reveals that adopting NGS after EGFR and ALK testing can deliver cost savings, in addition to identifying all actionable alterations which are linked to approved targeted therapies.
Despite researcher’s identification of exclusionary testing as the favourable molecular testing strategy in East Asia, they suggested that future developments could allow for upfront NGS to have a greater clinical and economical impact. “To allow for prompt selection of the most appropriate targeted treatment, and hence improve survival rates, it is crucial to identify these oncogene drivers in patients with NSCLC at diagnosis through molecular testing”, says Herbert H. Loong, lead author of the study.
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