Emphasizing the Need for NGS in Advanced NSCLC to Determine Treatment

CASE SUMMARY

A woman aged 72 years and never smoker presented to her primary care physician with a persistent, nonproductive cough; loss of appetite; and she experienced pruritus for 4 months. Her contrast-enhanced chest/abdomen/pelvis CT scan showed a 4.1×3.8-cm tumor in the left upper lobe with calcification and left hilar lymphadenopathy, but an MRI scan of her brain was negative for any intracranial activity. After the patient underwent a transbronchial biopsy, her immunohistochemistry panel came back negative for ALK and TPK1 mutations but was positive for TTF1. An antibody assay came back with a PD-L1 measurement of 25%. Her concurrent tissue- and plasma-based next-generation sequencing (NGS) panel was positive for an EGFR exon 21 L858R mutation and she was diagnosed with stage IV adenocarcinoma.

DISCUSSION QUESTIONS

• When do you test with NGS?​
• Would you consider a PD-1/PD-L1 inhibitor-based treatment in the first line for a patient with intermediate PD-L1 expression of 25% and a classical EGFR exon 19(del)/exon 21 L858R mutation?

JOSHUA SABARI, MD: [We use NGS] upfront; that's the key here. Historically, we were testing at [the time of] progression only and starting chemotherapy, but ever since the advent of immunotherapy and since it's entered the frontline, we need to test [for mutations] upfront. We can't wait [to test] patients when they’re in the second-line setting, and we know there are survival benefits for a lot of these targeted therapies in the frontline setting.

Joshua Sabari, MD

Assistant Professor, Department of Medicine

NYU Grossman School of Medicine

Director, High Reliability Organization Initiatives

Perlmutter Cancer Center

New York, NY

In this case, with a [patient who has a] PD-L1 expression of 25% and is a never smoker, if you don't have the results of the NGS testing back yet would anyone consider starting immunotherapy or chemoimmunotherapy? No, there would be no takers [in that situation], because everybody is going to wait for the NGS results and start the best possible therapy, and we certainly don't want to give the patient the wrong therapy. A lot of times, patients only have 1 potential line of therapy, and they don't have the ability to get further lines of therapy. We never know if someone's going to make it to the second line, so we want to use our best therapies first.

What if the patient had a PD-L1 expression of 100%? Would that change anyone's opinion [regarding their approach to treating the patient]?

JOSHUA STRAUSS, MD: No, I don't pay attention to the PD-L1 status in [patients positive for an] EGFR mutation.

SABARI: I agree. There’re many prospective trials [for these patients], such as including chemotherapy and immunotherapy after [the use of osimertinib (Tagrisso)], and unfortunately there's been no significant benefits in the EGFR-mutant patient population. So there's very little role for immunotherapy here, with the one caveat being the IMpower150 study [NCT02366143], which is the use of carboplatin, paclitaxel, and atezolizumab [Tecentriq] plus bevacizumab [Avastin].1 There are also data for patients post-disease progression on osimertinib that showed a potential benefit for the EGFR- and ALK-positive patient populations, but it's not a commonly-used regimen here in the United States. In China it's a commonly used regimen in the second-line setting.²

Does the presence of an EGFR L858R mutation vs an exon 19 deletion change anybody's approach as well?

BRUCE KAPPEL, MD: I don't get into that unless we get into the bizarre [mutations that require a very different approach].

AQEEL GILLANI, MD: I'm with Dr Kappel on that one. I don't think we get into the weeds [when we see these mutations]. I see exon 19 deletion and L858R EGFR mutations as identical. Some differences, but [not many].

REFERENCES:

1. Socinski MA, Nishio M, Jotte RM, et al. IMpower150 final overall survival analyses for atezolizumab plus bevacizumab and chemotherapy in first-line metastatic nonsquamous NSCLC. J Thorac Oncol. 2021;16(11):1909-1924. doi:10.1016/j.jtho.2021.07.009

2. Xu Z, Hao X, Wang Q, et al. Efficacy of osimertinib after progression of first-generation epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) in EGFR-mutated lung adenocarcinoma: a real-world study in Chinese patients. Cancer Manag Res. 20221;14:863-873. doi:10.2147/CMAR.S346173