Asia-Pacific Biotech News

A New Hope for Those With Rare Type of Lung Cancer

An interview with Dr Lim Hwee Yong, specialist medical oncologist with Novena Cancer Centre.

Asia is a diversified and densely populated region with around 4.75 billion people. According to the World Health Organization, cancer is the leading cause of death in Asia, accounting for millions of deaths each year. Lung cancer remains the leading cause of all cancer deaths. What are the current treatments available for lung cancer patients and how does Rybrevant address a rare type of cancer?

In this interview, we speak to Dr Lim Hwee Yong, specialist medical oncologist with Novena Cancer Centre, to find out more.


1. How prevalent is lung cancer in Asia and what are some types of lung cancers?

Lung cancer is one of the most common types of cancer in Asia, accounting for the highest number of mortalities in Asia and globally. In 2020, lung cancer was responsible for 1.8 million deaths in Asia/the world. In Singapore, lung cancer is one of the leading causes of cancer death, accounting for more than 25 percent in men and over 15 percent in women.1 Lung cancers are broadly divided into small cell and non-small cell types, with the most common types of non-small lung cancer includes adenocarcinoma and squamous cell carcinoma.


2. What are the current treatments available for lung cancer patients? Do they all work the same way for all patients with lung cancer?

Treatments for lung cancer include traditional medication therapies, infusion treatments, surgical and radiation treatments. Medications work in different ways. Cytotoxic treatments target rapidly dividing cells, relatively indiscriminately. Newer medical treatments target specific molecular differences that are present mainly or only on cancer cells. This results in more defined and specific targeting of only cancer cells. Currently available targeted treatments, like EGFR tyrosine kinase inhibitors (TKI) are generally insensitive in treating NSCLC driven by EGFR exon 20 insertion mutations and are not FDA-approved for these patients.2,3,4


3. Tell us more about this rare type of lung cancer, its survival rate, and its prevalence among Asian patients.

Non-small cell lung cancer accounts for 85% of all lung cancers. EGFR mutations are found in around 50% of Asian patients with non-small cell lung cancer. Exon20 insertion mutation is a rarer form of EGFR mutation and can be found in 4 to 10 % of non-small cell lung cancer harbouring EGFR mutations. In particular, these mutation is found more commonly in women, non-smokers, Asian population with adenocarcinoma histology. In addition, NSCLC driven by this mutation carries  worse prognosis and shorter survival rates compared with lung cancer driven by more common EGDR mutations, such as exon 19 deletions and L858R substitutions.5,6 Patients newly diagnosed with metastatic NSCLC with EGFR exon 20 insertion mutations have a real-world median overall survival (OS) of 16.2 months (95 percent confidence interval [CI], 11.0–19.4), which is lower than patients with EGFR exon 19 deletions/L858R mutations, who have a real-world median OS of 25.5 months (95 percent) CI, 24.5–27.0).7


4. How does Rybrevant target this rare type of lung cancer? How does it differ from other forms of treatment?

Rybrevant is an antibody engineered to bind on to the EGFR and MET receptors, and has been shown to have superior efficacy, compared to many other EGFR inhibiting medications, against exon 20 insertion mutation type of non-small cell lung cancer. As this drug is engineered to bind specifically to EGFR and MET receptors, this results in higher specificity and less side effects for the patients.


5. If I am newly diagnosed with lung cancer, how do I find out if I have this rare mutation?

This rare mutation can be detected using modern genetic extraction and sequencing technology. This process of detection can be performed on the extracted cancers cells from a piece of biopsied cancer sample, from circulating tumour cells or even from circulating tumour DNA in the blood stream.

As with many cancers with known genetic mutation drivers, comprehensive molecular profiling that identifies EGFR mutations and other molecular drivers is recommended to optimally guide targeted treatment decisions from initial diagnosis.8 PCR-based tests, which are mutation-specific, have technical limitations and can detect only a limited number of exon 20 insertion mutations.7,9,10

Comprehensive genomic profiling indicates that the prevalence of EGFR exon 20 insertion mutations has been historically under-diagnosed due to technical limitations of currently available PCR-based assays, with PCR-based assays missing approximately 50 percent of mutations.7,9,11 Because of the limited use of NGS-based tests, these mutations often go undetected.7,11 The large number of exon 20 insertion variants identified suggests that NGS platforms, whether academic or commercially available, would improve the exon 20 insertion detection rate by capturing the full breadth of variants that have been identified.7,11 NGS-based tests of liquid biopsies can serve as a complement to tissue-based NGS testing to detect alterations in tumours that cannot be biopsied.11 [APBN]

This article was first published in the March 2023 print version of Asia-Pacific Biotech News.

About the Interviewee

Dr. Lim Hwee Yong is a specialist medical oncologist with Novena Cancer Centre. He was previously consultant medical oncologist with National Cancer Centre Singapore, visiting consultant medical oncologist to Changi General Hospital and President of Singapore Society of Oncology. Dr. Lim received his medical degree from University College Dublin, National University of Ireland, whereby he won the prestigious Ambrose Birmingham Medal in Anatomy and various university scholarship programmes. He did his postgraduate training in Internal Medicine at the University of Hawaii and Hematology and Medical Oncology training at Huntsman Cancer Institute, University of Utah. Dr. Lim holds the American Board Certification for Internal Medicine, Hematology and Medical Oncology.