Sequist Calls 2020 a Banner Year in Lung Cancer, But Leaves Much to Be Desired

The read out of the NELSON trial and the FDA approvals of adjuvant osimertinib (Tagrisso) and the combination of nivolumab (Opdivo) and ipilimumab (Yervoy) with or without chemotherapy were some of the major advances of 2020 in lung cancer, according to Lecia V. Sequist, MD, MPH, who cautioned that the stigma surrounding screening, institutional protocols for genetic testing, and ongoing research regarding biomarkers of response will have to be addressed if the field is to reap the demonstrated benefits of each intervention. 

“It was really a year of amazing advances across the spectrum of treatments for lung cancer, and I hope that this pace of discovery and advances that really make a difference for the lives of our patients continues with gusto in 2021 and beyond,” said Sequist.

In an interview with OncLive^® during a 2020 Institutional Perspectives in Cancer webinar on lung cancer, Sequist, the Landry Family Associate Professor of Medicine at Harvard Medical School, and director, Center for Innovation in Early Cancer Detection, Massachusetts General Hospital, discussed some of the biggest advancements of 2020 in lung cancer.

OncLive^®: What were some of the biggest developments of 2020 in lung cancer?

Sequist: 2020 was an amazing year for lung cancer, despite everything going on with the pandemic. Several new drugs were FDA approved; 2020 was an unprecedented year for approvals in lung cancer. Several key clinical trials read out and were presented.

In early-stage lung cancer, the NELSON trial was presented [and published] in the New England Journal of Medicine. This was a screening trial that confirmed the benefit of low-dose CT scans, confirming in an independent group what the NLST [National Lung Screening Trial] study showed us. That’s really important for getting screening going more globally. 

Secondly, the ADAURA results for adjuvant osimertinib in resected, EGFR mutation–positive patients were presented and published, [and the drug received] FDA approval all in 2020. That is a really great advance [and] the first time we’re seeing targeted therapy used in the early-stage setting successfully. This will be a blueprint for other treatments to come for other specific subgroups of lung cancer.

For different subgroups of lung cancer in 2020, we saw FDA approvals for several different drugs, some of which were the first in that subtype. For example, RET inhibitors were approved for the first time in 2020. There’s selpercatinib [Retevmo] and pralsetinib [Gavreto]. Capmatinib [Tabrecta] was approved for [patients with] MET exon 14 skipping mutations––also a first and a landmark in lung cancer.

New [immunotherapy] regimens were also approved, such as the [combination of] nivolumab and ipilimumab or that same combination with chemotherapy. 

Despite the data from NELSON and NLST, screening rates remain low. How could the anticipated revisions to current screening guidelines affect current practice? 

[Screening guidelines] would be broadened [with the revision], and that’s a good thing. But you’re right, and there are 2 separate problems. First, there’s a general disbelief or failure to embrace the concept of lung screening, and then there’s the question of which population is the most appropriate for screening or will get the most bang for the buck. The issue of why we as a global society have failed to embrace lung cancer screening is complicated, and I can’t pretend to fully understand it.

I think many factors are involved, some of which are political, some of which are ingrained stigma against lung cancer. Unfortunately, when the NLST first came out, several professional societies were vocal about not thinking that this would be helpful, and even though a lot of their arguments have been debunked, that sort of sentiment has stuck around. 

I do agree with the premise of the question, which is that scientifically, it’s proven to be quite helpful, more so than mammography and more so than colonoscopy. The number needed to screen to save one life is much lower with lung cancer screening. However, this other issue of exactly who do we screen is an important one that kind of ties into our enthusiasm about screening, because the current screening guidelines and even the proposed broader guidelines still focus essentially on smokers. 

[The guideline committee] are lowering the age limit, and they’re lowering the number of pack years needed to qualify, but it’s still a fairly significant smoking history that’s required [for screening]. At the same time, what we’re seeing in the oncology clinics is more and more patients coming in the door with newly diagnosed lung cancer that wouldn’t have fit the criteria for screening because they’re too young or more often because they don’t meet the screening [criteria] at the smoking cutoff. Understanding that this disease is changing epidemiologically, that it is coming up in people who didn’t smoke or who smoked and quit decades ago, who no longer qualify for lung cancer screening [is critical]. We have to figure out better ways to understand who is at risk and how to screen them if we want to find cases in an earlier stage when they’re more curable.

How are you navigating patient discussions now that osimertinib is approved for use as adjuvant therapy for those with EGFR mutations? Are patients interested in receiving the drug despite the unknown overall survival (OS) benefit?

For the most part, yes, although I have encountered at least one patient in my clinical practice who was hesitant [about receiving the drug], and I think that’s fair based on the data. [The ADAURA trial showed a] DFS [disease-free survival] benefit [but] no OS benefit. There’s a lot of enthusiasm that it can be helpful, but we don’t know for sure that it improves the cure rate yet. Having a discussion about what we know and what we don’t know with each patient is the most patient-centric way to move forward.

From a logistical standpoint, what’s really important for different hospitals to consider is how they’re going to test the surgically resected samples. Each practice has gotten into their own groove and their own system for doing genetic testing for more advanced patients. However, for early-stage patients, it’s often a totally different protocol that’s used. Genetic testing hasn’t currently been part of the reflex pathway for the tissue to travel toward.

In my own hospital, we’re just testing for EGFR mutations in our resected patients. Other hospitals have chosen to do NGS [next-generation sequencing], looking at lots of different mutations. It’s a matter of figuring out what works best at your institution and what’s going to be covered and what’s going to be cost prohibitive. We’ve been doing that for a couple of months now, and I found that it works really well.

Usually by the time I’m seeing a patient who has had surgery, when I’m seeing them in the medical oncology clinic, I have the EGFR mutation results already, and we can talk about adjuvant chemotherapy, which is still really important, if they qualify for that, and then following adjuvant chemotherapy with adjuvant osimertinib, if they have the mutation. Patients, in my experience so far, feel like they’re really getting everything possible to prevent their cancer from coming back.

How much more complicated have treatment decisions become with the additional approvals of immunotherapy in the metastatic setting?

I would say a lot more complicated. It’s really become apparent that you can’t just extrapolate 1 trial against the other. What you can say from each trial is [among] the 2 arms that were designed and directly compared, one was superior, and one was inferior, but you can’t always compare that with another treatment that wasn’t part of the trial design.

Now that there are so many different immune, immune/chemotherapy, immune/immune combinations approved for lung cancer, there have gotten to be a lot of nuances. At the same time, everyone’s sort of holding with patterns of practice from about 1 year ago until there’s more follow-up with some of these newer studies. What I tend to see in my practice, and my colleagues that I work with, is that there’s still a lot of single-agent, mostly pembrolizumab [Keytruda], use if patients have a high PD-L1 level. A lot of combinations like carboplatin/pemetrexed and pembrolizumab are still used if [patients] have less than 50% PD-L1 [expression].

How we incorporate TMB [tumor mutational burden] into our clinical decision making is still really unknown. People agree that it’s important and that it probably has some meaning, but there’s a lot of disagreement about exactly how to interpret those results, or how they should impact your decision making. It’s exciting that we have a lot of treatments, and over the next 1 to 2 years, hopefully there will be more guidance from newer trials that are coming out that will help us make these decisions with our patients.

Editor’s Note: This interview was conducted prior to the International Association for the Study of Lung Cancer 2020 World Conference on Lung Cancer.