Unmet medical needs and emerging data on EGFR exon 20 insertion mutation NSCLC at ASCO 2021

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Published: 16 Jul 2021
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Prof Caicun Zhou - Shanghai Pulmonary Hospital, Shanghai, China

Prof Caicun Zhou speaks to ecancer about the unmet medical needs and emerging data on EGFR exon 20 insertion mutation non-small cell lung cancer (NSCLC) at ASCO 2021.

Initially, he describes the current situation regarding the treatment of EGFR exon 20 insertion mutation in NSCLC.

Prof Zhou then discusses the studies released at ASCO 2021 within this patient population and how the study results can address the unmet medical needs. In the end, he talks about what does the future looks like for EGFR exon 20 insertion NSCLC treatment.

Mobocertinib (TAK-788) in EGFR ex20ins + mNSCLC
Amivantamab compared with real-world therapies in patients with NSCLC with EGFR ex20ins mutations
Safety and activity of CLN-081 and DZD9008
Future of the treatment for EGFR exon 20 insertion mutation NSCLC

 

This programme has been supported by an unrestricted educational grant from Takeda.

ecancer's filming has been kindly supported by Takeda through the ecancer Global Foundation. ecancer is editorially independent and there is no influence over content.

As we all know, for patients with sensitive EGFR mutation we have first gen, second gen and even third gen EGFR tyrosine kinase inhibitors. These compounds do much better than chemotherapy in terms of progression free survival, tumour response rate and safety profile. Now we have enough data to show that the patients with EGFR exon 20 insertions account for about 2% of the total of lung cancer. This mutation, EGFR exon 20 insertion, occurs mainly in never smokers with adenocarcinoma. Up to now there is no targeted therapy for them; in our daily practice we just treat them with doublet chemotherapy and you all know that the efficacy of the chemotherapy is quite marginal. The median progression free survival is only about 4-6 months, overall survival around one year. Clearly there is an unmet clinical need in this population – we need a better compound, especially a targeted agent, to treat this population.

What data released at ASCO 2021 addresses unmet needs in this patient population?

The study was reported by Dr Ramalingam on TAK-788, or mobocertinib, in the second or later line of treatment in patients with EGFR exon 20 insertions. The sample size is over 100 cases, it’s not just the phase II study in this population. We got an excellent tumour response rate of around 25-28% and progression free survival is 7.3 months. These two parameters were better than chemotherapy, especially progression free survival. The disease control rate is over 80%; overall survival is over one year – much better than chemotherapy. When we look at duration of response which is 17.5 months, so a very longer duration of response.

Efficacy is acceptable in this patient population. When we look at the safety profile we do find the therapy is associated with diarrhoea, skin rash, paronychia and decreased appetite but the majority of patients just develop grade 1 or grade 2 diarrhoea, skin rash and paronychia. Only less than 10% of patients develop grade 3 or higher skin rash, diarrhoea and paronychia. These three major adverse events could be manageable in our daily practice. We are lung cancer doctors, we use a lot of EGFR tyrosine kinase inhibitors so these adverse events associated with mobocertinib are often observed with other EGFR tyrosine kinase inhibitors, especially second generation EGFR tyrosine kinase inhibitors such as afatinib and dacomitinib. So I would say that we are expert in managing these adverse events, I mean diarrhoea, skin rash and paronychia. That’s my comment on this study so I do think that mobocertinib is a good compound and should be the first tyrosine kinase inhibitor for patients with exon 20 insertions.

Actually we have amivantamab, the bispecific. This compound produces about a 40% tumour response rate, about 8.3 months of progression free survival. The efficacy is acceptable and also comparable to those of mobocertinib. The compound is approved in the United States; I do think the compound will be approved in China.

For the other two compounds such as CLN-081 and DZD9008, these two compounds are just EGFR tyrosine kinase inhibitors. In their phase I/II study we found these compounds worked in patients with exon insertions but we need a large sample size to confirm the efficacy observed in the phase I trial. So I think in the near future we will have several EGFR tyrosine kinase inhibitors for the patients with EGFR exon insertions. We will also have several bispecifics available to treat this population.

What does the future look like for EGFR exon 20 insertion NSCLC treatment?

We have a great opportunity in the near future. We have several compounds on the way in our daily practice. The first one should be bispecifics against EGFR and cMET. Amivantamab – the compound has been approved in the United States; the compound has similar efficacy compared with that of mobocertinib. The second compound should be mobocertinib. We have very good efficacy data and an acceptable safety profile; I do think the compound will be approved very soon in the United States as well as in China.

Then there are several compounds that are just in early phase clinical development. These compounds just have very preliminary data in the phase I and phase Ib. The efficacy is acceptable, the safety profile may be improved compared with mobocertinib but these compounds are just in the early stage of clinical development. We need a large sample size study to confirm efficacy of these compounds.

So, for the patients with exon 20 insertions we can have very good compounds for them. That’s very important for our patients, it’s also very important for our doctors. We can use them to treat our patients, that’s my suggestion. Thank you very much.