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ASCO 2021 Lung cancer: Clinical insights into key research

Gilberto Lopes shares his lung cancer highlights from the 2021 ASCO Annual Meeting, including the IMpower010 trial, the MYLUNG study of real-world molecular testing, and updates on the CodeBreaK 100 and CHRYSALIS studies (8:06).

00:00 – Introduction
00:30 – MYLUNG study
02:44 – CodeBreaK 100 trial
03:52 – CHRYSALIS trial
04:48 – IMpower010 trial

Hello. Thank you very much for having me talking about highlights for ASCO 2021. This was its second virtual meeting. And without a doubt, this was a very important meeting for lung cancer as well. We had a number of interesting studies that were presented or updated. And it’s my pleasure to discuss some of these with you today. The most important one may be the data on adjuvant immune checkpoint inhibitors with atezolizumab IMpower010, but let me talk about a few other things first.

So first, in terms of testing, we had a very interesting study from the US Oncology Group here in America. And the reason that was interesting is because we do hear and we do know when we do second opinions and when we talk to colleagues across the country that even here, not everybody gets comprehensive next-generation sequencing for the lung cancer patients before starting therapy. So we do know that most patients do get tested for EGFR, ALK, and maybe ROS1, but we did not have an idea of what percentage of patients got tested for more comprehensive genome analysis.

And this study definitely shows us that about half of the patients at least are not getting the comprehensive analysis with all of those biomarkers, all of those driver mutations that we now have therapies for. So when we look at EGFR, yes, most patients do get tested. But when we look at less common things for which we now have medications such as RET translocations, or NTRK, or MET exon 14, BRAF, and now, of course, KRAS G12C, we do not have enough people being tested.

In addition to that, we had just published at a special edition of JCO Oncology Practice our metaanalysis showing that, for a few thousand patients of African-American or Afro-Caribbean, descent we saw that EGFR mutation rates are much lower than what we come to expect in Caucasian patients as well as in Asian or Hispanics, which is a kind of intermediate between Caucasians and Asians. But what was interesting at ASCO 2021 is that not only do Black patients have a lower prevalence of EGFR and ALK, EGFR mutations and ALK translocations, but you also have a lower prevalence of testing. So this is in line with ASCO’s theme of equity for the 2021 meeting. This shows us that we have a lot of work to do in this country still in terms of testing, not just for minorities, but for all population in general, as well.

A few more very interesting studies were represented in the targeted agent realm, as I mentioned, KRAS G12C. We have updated data from sotorasib, the CodeBreaK 100 study. And what that shows us is that it confirms that response rates that we saw and that were presented in prior meetings.

And we also now have data for median duration of response, median progression-free survival, and overall survival data, at least preliminary for now. And this is clearly something that is here to improve the lives of our patients. It does seem to improve outcomes. We clearly see response rates are in line with what we used to see in first-generation EGFR and ALK inhibitors, for instance.

It doesn’t seem to be as effective as we have come to expect for newer generation tyrosine kinase inhibitors for EGFR and ALK, but these G12C inhibitors which do not block tyrosine kinase– they’re actually cysteine inhibitors. They block the cysteine residue. They do seem to have activity. And they should become standard of care for patients.

In terms of other studies, we also had what now is the new frontier in targeted agents. We need to circumvent and treat resistance. And we had a few studies that were really interesting in terms of trying to combat resistance for patients with EGFR inhibitors.

We had trials looking into new drugs such as “avantamab” in combination– amivantamab, which is hard to pronounce, in combination with lazertinib. So amivantamab is a fully human bispecific monoclonal antibody that targets both EGFR and MET, which has been implicated in resistance mechanisms for patients after therapy with osimertinib. And lazertinib is a third-generation EGFR inhibitor. And the combination clearly showed responses, and more likely have a role, and will likely become part of our armamentarium in the next year or so.

We also had other interesting studies at ASCO, but as we do not have too much time, let me focus on what maybe was the most important study, which is in the immunotherapy realm. And it’s called IMpower010, this is the first study to be reported looking into clinical outcomes for patients who received adjuvant chemotherapy and then are randomized to receive adjuvant immunotherapy or not. So this is a trial with atezolizumab, which is one of the checkpoint inhibitors we have available for patients with metastatic disease.

And this was extremely interesting, but this is going to be a study we’re going to be debating for quite some time, because the accepted endpoint was actually disease-free survival. This had a hierarchical statistical analysis plan, so it is a little bit more confusing and complex. So overall survival only becomes the endpoint if three disease-free survival analyses actually get through. And so far what we have had time to have adequate data in terms of median follow up is for the disease-free survival in PD-L1-positive patients and then of course the disease-free survival in all randomized patients.

The data clearly show the benefit for the population with a PD-L1 of 1% or greater. And there, the hazard ratios are good enough to suggest that this is a clinically significant, not just statistically significant, but also clinically relevant benefit. And this will most likely lead to approval for atezolizumab in the adjuvant setting, at least in the United States in the next few months. We will debate for quite some time, because we don’t know if this disease-free survival benefit is going to translate into better overall survival and better cure rates, which, of course, is what we are looking for when we do adjuvant trials. But I think that the benefit that we see in terms of the hazard ratio, there clearly is a benefit.

It’s not so clear if the benefit exists for those patients that do not express PD-L1. And what’s not clear is if most of the benefit is driven by those patients that actually express more PD-L1. So what truly is the population that’s benefiting?

Is it the ones that express 50% or greater? Is it between 1% and 49%? And so these are the data, these are the numbers that we’re going to need to see moving forward to be able to know which patients are going to benefit the most.

But I think that as the trial was designed, disease-free survival is an important endpoint. It’s not as important as overall survival, but it is an endpoint that we can get earlier than we would get overall survival data. So we will most likely be using. And we’re going to have a lot of debate in the next few months about which patients would benefit the most and we should use it or not.

And I think that this is kind of a wrap up for what we saw in lung cancer at ASCO. This was without a doubt a very important year for lung cancer at the ASCO meeting. And I’m looking forward to being in touch and seeing you guys in real-world meetings as we move forward.


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Lucy Piper

medwireNews Bureau Chief

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