Prof Chao-Hua Chiu shares insights on the application & clinical implementation of NGS for lung cancer treatment decision-making

Interview transcript:

Introduction

I’m a pulmonologist as well as a medical oncologist. I work in the Taipei Cancer Centre, Taipei Medical University in Taiwan. I work on lung cancer for 20+ years, and mostly I’m more interested in lung cancer screening and treatment in late stage lung cancer in early phase novel drug development clinical trials.

In the current healthcare situation in Taiwan, what are the most urgent needs for managing patients with lung cancer?

The first one is to identify the patient as early as possible. Lung cancer screening is a very important part in the control of cancer. Especially in Taiwan, about half of the newly diagnosed lung cancer are never-smokers. In Taiwan since about 1 year ago, last July, our government decided to initiate a national lung cancer screening program that include not only heavy smokers, but also non-smokers for those who have first-degree lung cancer family, as far as I know that is the first in the world in national lung cancer screening, that enrolled never-smokers with risk. Based on a recent study that will be published soon, showing that low dose CT lung cancer screening will be helpful for those with never-smokers, but with lung cancer risk. To find the patient in the early stage, and for those early stage lung cancer, surgery alone will be enough. The more challenging part of the management of lung cancer is when the disease goes to the 2nd or 3rd or the 4th stage. For those with locally advanced lung cancer, the recurrence rate after surgery is high, so we have to give neo-adjuvant and adjuvant treatment. We have EGFR-TKI in adjuvant setting, that is proven to give survival benefit after surgery. We also have neo-adjuvant or adjuvant immunotherapy, that also prove to provide survival benefit to the patient after or before surgery.  For those with stage 4 disease, it is complicated. In non-small cell lung cancer (NSCLC), the most important one is to find the driver mutation. So it is a most critical step in the management of late stage NSCLC.  We need a panel of testing to find out the driver mutations. So NGS, next-generation sequencing, it will be a must do testing in the near future.

How has the lung cancer screening in Taiwan helped to improve early diagnosis of lung cancer and improve patient outcomes?

The distribution of stages in NSCLC is roughly about 20% stage 1, 10% stage 2, another 10% stage 3, and more than 50% of the newly diagnosed cases are stage 4. But after the implementation of low-dose CT screening in Taiwan, in some medical centres, stage 1 lung cancer is reaching to 30 to 40%. We believe we will see lung cancer mortality will significantly improve after 5 or 10 years that is simply because we find more early stage lung cancer and less stage 4 lung cancer. It’s just because of the screening, result in stage shift, that will give a significant reduction of lung cancer mortality.

In your opinion, what are the key benefits of precision oncology in real-world clinical practice, especially for patients with lung cancer?

NSCLC is probably the [cancer to] most benefit from NGS. Driver mutations caused the lung cancer, And these driver mutations are usually mutually exclusive. NSCLC is no longer to be classified according to histology.  Nowadays NSCLC may be classified according to the underlying mutation because we treat the patient according to the underlying driver mutation. So if we want to check these 10 driver mutations one by one, it not only takes time but also takes money to do all these tests. More importantly, it takes tissue, and tissue is more precious than money or time. So we need a platform that can do multiple gene mutations simultaneously.

What are some of the challenges you currently face for precision oncology realisation in your clinical practice?

We know the benefit and the importance of NGS testing, but to be honest, only very few patients can get NGS testing at the beginning in Taiwan. The testing is expensive, and it is not yet reimbursed by the health system in Taiwan. So luckily, just a few weeks ago our government, they decide to reimburse NGS testing in the coming year. If it comes true, our patient will benefit a lot from this reimbursement policy change. From the scientific point of view, some diagnostics or treatment are certainly beneficial to the patient, but because of the budget impact of our health system, very few countries can fully reimburse all these treatment or diagnostics, so that’s a major hurdle of the management of NSCLC at this moment.

What are some solutions which may help address these challenges?

If we know how to treat the patient but the patient cannot afford it, that is a tragedy to the patient and his family. If the government and the Pharma industry can get some agreement to get the new drugs to be on the market as soon as possible, it will be a critical step to improve the overall patient outcome. For example, in UK, there is a system called Cancer Fund. The new drug can be in the market as soon as the drug gets approved and the government will re-evaluate the treatment efficacy, or the cost-effectiveness of the treatment. And then they can decide to get the drug so-called fully reimbursed or not. In Taiwan, our government also considers this so-called alternative reimbursement pathway, so that the patient can get the drugs. The doctor knows which drug is a treatment of choice but just just cannot get the drug. So how to get the drug as early as possible is very important, especially to a stage 4 lung cancer patient.

With new advancements in lung cancer and precision oncology, what are your future expectations for patient management in lung cancer? How do you see this field evolving over the next few years?

The precision medicine is not only at the treatment, but also at the management of health. So technology wise, I believe the AI technology will certainly play some role in the diagnosis as well as the treatment. And the other technology that we expect is the liquid biopsy, because not all patients can get enough tissue to do NGS testing. I believe in the very near future we just take 1 or 2 millilitres of blood, and then we can check mutations, and not only at the beginning, but also during the treatment, we can serially check the mutation status to decide whether the treatment can continue or the treatment should be changed. I think this technology will come in soon.

The views and opinions expressed by Prof. Chao-Hua Chiu are his own views and opinions. Roche disclaims all liability in relation to these views and opinions.

Quick Summary

In Asia, guidelines for the management of patients with mNSCLC currently recommend the use of targeted therapies acting on driver oncogene alterations such as EGFR, ALK, ROS1, and BRAF V600E, as well as PDL-1. Despite current recommendations and addition of therapies targeting new alterations (like MET and RET), the rate of molecular testing in East Asian patients with NSCLC varies considerably.

To ensure patients receive optimal treatment that improves patient survival, the implementation of effecient and cost-saving molecular testing strategies in East Asian clinical practice needs to be improved. Therefore, it is particularly important to evaluate the efficacy and economic value of upfront NGS versus other testing modalities in East Asia, to determine whether NGS is the most cost-saving strategy in the first-line setting.

Using Hong Kong as an example, this study aimed to evaluate the economic impact of upfront NGS compared to exclusionary, single-gene sequential, and hotspot panel testing modalities in East Asian patients with mNSCLC. A budget impact analysis was also conducted to evaluate the financial impact of adapting upfront NGS from the Hong Kong payer’s perspective.

Quick Summary

The most recent version of the European Society for Medical Oncology (ESMO) Clinical Practice Guidelines for the diagnosis, treatment and follow-up of early and locally-advanced non-small-cell lung cancer (NSCLC) was published in 2017, and covered the diagnosis, staging, management and treatment of both early stage I and II disease and locally-advanced stage III disease. At the ESMO Asia Meeting in November 2018, it was decided by both the ESMO and the Korean Society of Medical Oncology (KSMO) to convene a special face-to-face guidelines meeting in 2019 in Seoul.

The aim was to adapt the ESMO 2017 guidelines to take into account potential differences related to ethnicity, cancer biology and standard practices associated with the treatment of locally-advanced, unresectable NSCLC in Asian patients. These guidelines represent the consensus opinions reached by those experts in the treatment of patients with lung cancer who represented the oncology societies of Korea (KSMO), China (CSCO), India (ISMPO), Japan (JSMO), Malaysia (MOS), Singapore (SSO) and Taiwan (TOS). The voting was based on scientific evidence, and it was independent of both local current treatment practices and the treatment availability and reimbursement situations in the individual participating Asian countries.

Quick Summary

Most published guidelines for genomic biomarker testing in NSCLC reflect the disease epidemiology and treatments readily available in Europe and North America. Nevertheless, 60% of annual global NSCLC cases occur in Asia, where patient characteristics, tumor molecular profiles, and treatments vary greatly from the Western world. For example, mutations in the EGFR occur at a higher prevalence in Asia than in other world regions. Although medical associations such as the International Association for the Study of Lung Cancer, European Society for Medical Oncology, and American Society of Clinical Oncology have described principles for tumor genomic biomarker testing in NSCLC, there is a need for recommendations specific for Asia.

This report provides consensus recommendations for NSCLC biomarker testing from Asian lung cancer experts for clinicians working in Asia to improve patient care. Biomarker testing approaches for actionable genetic alterations in EGFR, ALK, ROS1, and others are discussed for nonmetastatic and metastatic forms of adenocarcinoma and squamous cell carcinoma.