Targeted Therapies and Expanded NGS Access Improve Decision Making in Lung Cancer

Melissa L. Johnson, MD

Several paradigm shifts have occurred in non–small cell lung cancer (NSCLC), among them the advent of immunotherapy in platinum-ineligible patients and the increasingly widespread availability of biomarker testing, according to Melissa L. Johnson, MD.

“The overarching message [from this meeting] is that lung cancer is getting more complicated, and it’s not 1 illness,” Johnson said in an interview with OncLive^® following an Institutional Perspectives in Cancer (IPC) webinar on lung cancer, which she chaired.

In the interview, Johnson shared key insights from the meeting, including pertinent findings in KRAS G12C­–mutated NSCLC from the phase 3 CodeBreak 200 study (NCT04303780) and positive findings with atezolizumab (Tecentriq) in platinum-ineligible patients with NSCLC. She also shared the importance of next-generation sequencing (NGS) in personalized medicine and how moving lung cancer treatments to earlier lines has improved patient resectability rates.

Johnson is the director of lung cancer research at Sarah Cannon Research Institute and chair of the Cancer Committee at TriStar Centennial Medical Center, both in Nashville, Tennessee.

OncLive^®: What were some of the main themes that you and your colleagues discussed during the IPC meeting?

Johnson: I discussed both immunotherapy in the frontline setting for patients with NSCLC and targeted therapies for patients with lung cancer. We separate lung cancers now based on histology, as well as molecular profile and PD-L1 status.

All this information is incredibly important. The sooner you know the various biomarker results, the better able you are to help select the right frontline therapy. What’s becoming clearer is how important all the biomarker testing is up front. This is also a challenging time.

[I talked about] the reasons to do the testing. What are the data for patients with PD-L1–high tumors vs PD-L1–low tumors or non-expressing PD-L1 tumors? How do you decide between a single-agent PD-1 or PD-L1 inhibitor vs a chemotherapy/immunotherapy combination vs a CTLA-4 inhibitor, PD-1 inhibitor, and chemotherapy combination?

Turning to the targeted therapies, many new therapies have been approved in the past year or so, about 7, spanning several targets, including EGFR exon 20 insertions, HER2 mutations, and KRAS G12C mutations. RET is still a mutation that we find occasionally, and it has 2 great treatment options. Being able to identify all the potential drivers is important so we can assign therapy appropriately.

[At this IPC meeting, I was joined by] Wade T. Iams, MD, [of Vanderbilt University Medical Center in Nashville, Tennessee]. He discussed small cell lung cancer [SCLC] management, another area that’s super exciting and on the cusp of some important breakthroughs. He talked about immune therapy and lurbinectedin [Zepzelca]. [He also noted] the subtypes of SCLC [and their corresponding treatments].

Denis M. Gilmore, MD, [of Maury Regional Medical Center in Columbia, Tennessee,] discussed the role of surgery for lung cancer. We’re thinking about neoadjuvant therapy [in the form of] chemotherapy and immunotherapy for many more of our patients. [Dr Gilmore talked about] what goes through his mind [when treating] patients on our tumor board, where we ultimately might decide to give a trial of induction chemotherapy and immune therapy.

We also heard from the [Sarah Cannon] director of personalized medicine, Andrew McKenzie, PhD. He’s always a great addition to any [IPC meeting]. The Tennessee Oncology doctors use him to help understand their NGS assays and what to do about them. His talk helped bring all the other data together.

At the 2022 ESMO Congress, you presented the results of CodeBreak 200. What is the significance of these data?

CodeBreak 200 was a randomized trial in which patients with previously treated NSCLC harboring KRASG12C mutations were randomly assigned to either the oral KRAS G12C inhibitor sotorasib [Lumakras] or standard second-line docetaxel. The primary end point was progression-free survival, and we showed a 34% reduction in the risk of disease progression or death for patients treated with oral sotorasib as opposed to intravenous chemotherapy.

We also showed improved safety and tolerance for patients who were treated with the oral agent, and, importantly, patient-related outcomes showing that this drug is better tolerated and preferable for patient quality of life. These were all important end points [that I reviewed at the IPC meeting].

In terms of immunotherapy, we also saw the results of the phase 3 IPSOS trial (NCT03191786) with atezolizumab in platinum-ineligible patients. What is the significance of that study?

That was an interesting study. For years, we have tried to show that platinum-based doublet chemotherapy is probably better than single-agent chemotherapy, so we should be treating all patients with platinum-containing regimens, irrespective of age and performance status.

This study turned all that on its side and [noted that] some patients still can’t receive platinum for [reasons such as] kidney function or hearing-impaired neurotoxicity from other comorbidities. For those patients, what’s the right choice?

The trial randomly assigned patients to single-agent atezolizumab vs the single-agent chemotherapies gemcitabine and vinorelbine. In this trial, patients did better with atezolizumab, suggesting that maybe single-agent immunotherapy, PD-1 or PD-L1 inhibitors in this case, is the preferable option, as opposed to platinum-based doublet chemotherapy.

Regarding Dr McKenzie’s presentation on personalized medicine, what is important to remember about the practical elements of personalized medicine that may get lost in all the exciting data we’re seeing come out in this area?

It’s easy to get overwhelmed with all the decisions and new drugs that are available in lung cancer. NGS makes your decisions easier. The practical lesson is that NGS testing helps separate [the options and helps you decide] whether immunotherapy, chemotherapy, or targeted therapy is appropriate.

Furthermore, we used to look at NGS as something that was done by those who have [it available], but many others [did not have it]. Plasma-based NGS has been a great equalizer in getting some NGS testing early for our patients. All patients can get that before [decisions about] treatment options need to be made. The turnaround time for liquid NGS is so much shorter. Tissue-based NGS is always going to be the gold standard, and it can be done subsequently.

[The main message from] Dr McKenzie’s talk and from my experience with NGS testing is that it’s not as hard as it used to be, and it actually makes things simpler rather than more difficult, compared with [the available methods] in years past.

With regard to Dr Gilmore’s talk, how has the utility of surgical intervention changed with the movement of systemic therapy into earlier disease states, especially given the phase 3 CheckMate 816 (NCT02998528) data and the results from the phase 2 NEOpredict study (NCT04205552) that were presented at ESMO?

It certainly is changing the multidisciplinary care of every patient who’s discussed at my tumor board, for example. Before, we always used the following situation: in the mediastinum, [we looked for] cancer in the M2 lymph nodes and how much to determine whether patients [received] induction followed by surgery or chemoradiation.

Now, the data from ESMO, especially, are tempting us to see whether we can make patients resectable. That was 1 of the most interesting discussions at ESMO. It’s taking the premise that you can know a patient’s resectability from the outset, and [that their resectability] won’t change, and turning that on its head. This is potentially opening [the doors] for more patients to experience cure, and that’s exciting.