New Lung Cancer Treatment Options Combine Neoadjuvant and Adjuvant Therapies

Misako Nagasaka, MD, PhD, Associate Clinical Professor in the Division of Hematology/ Oncology in the School of Medicine at the University of California, Irvine

Misako Nagasaka, MD, PhD, recently moderated an Around the Practice discussion about biomarker testing, the current treatment options for patients with non–small cell lung cancer who have EGFR mutations, and adverse effect management. She discussed these topics with CancerNetworkand highlighted new treatment options in the lung cancer space and the importance of multidisciplinary care, which included working with colleagues to provide the best possible care for patients with lung cancer.

At your institution, what are the current treatment sequencing options for lung cancer?

That would depend on the stage. Assuming that we’re talking about the advanced metastatic stage, I would want to know the molecular biomarkers. Does the patient have an EGFR or ALK mutation? What is the PD-L1 status? For patients who have a molecular target, I would like to use targeted therapy up front. If they do not have a target, I would be looking at the PD-L1 score. If it’s high and the tumor burden isn’t that much, I would start with single-agent immunotherapy. If not, I would be doing chemotherapy and immunotherapy.

Can you discuss the importance of multidisciplinary care in the space?

Multidisciplinary team care is everything, especially now that we have more and more data coming out in the neoadjuvant and adjuvant space. It’s important in all patients, not just patients with advanced metastatic stage but even [those] in early stage too, that we talk about what their best approach would be. [For example], the pulmonology team will [perform a] biopsy [for] someone, and if [the result] comes back as lung cancer, [the team will] present the case to our tumor board. Then we talk about the different scenarios that the patient could take. We talk about the advantages and disadvantages of each approach. It’s important to have that discussion early on. Sometimes, even if the patient didn’t qualify for surgery up front, now that we have better treatment [options] coming out, I have had times where our surgeons take the patient to surgery for residual disease resection. That’s an approach we can use as well. It doesn’t matter what stage; it’s important to have that multidisciplinary type of care.

Looking forward, how do you hope to see the field evolve in the next 5 years?

With more potent treatment options that are becoming available to patients, I hope that, in the next 5 years we have more patients [whom] we’re able to put into [disease] remission or even cure, even in the advanced or metastatic stage. I am also interested in trying to find these patients at an earlier stage because the lung cancer screening program is only for patients who have smoked at some point in their lives. Patients who have mutations, [such as] EGFR or ALK, tend to never smoke or be light smokers, and they don’t qualify for the traditional screening criteria. Coming up with a program to find these patients and help these patients early on is going to be key, and I hope that happens in the next 5 years.

The FDA recently approved neoadjuvant pembrolizumab plus chemotherapy for resectable non–small cell lung cancer. How will you begin to implement this into your practice?¹

It’s exciting to be a thoracic oncologist because every time I look around, there is a new approval that comes around. The data were interesting, and they complement what we had and what we didn’t have. We did have phase 3 CheckMate 816 [NCT02998528] data that included neoadjuvant chemoimmunotherapy.² We also had [the] phase 3 PEARLS/KEYNOTE-091 [trial] [NCT02504372], which was adjuvant pembrolizumab [Keytruda].³ We also had [the] phase 3 IMpower010 trial [NCT02486718], which was adjuvant atezolizumab [Tecentriq].⁴ We didn’t have clinical trial–based data on what would happen if patients were given neoadjuvant followed by adjuvant [therapy], so the new approval is exciting to us. It wasn’t just the disease-free survival that interested me. In the phase 3 KEYNOTE-671 study [NCT03425643], the most important curves were the Kaplan-Meier curves that showed patients who had a pathological complete response [pCR] or those who didn’t.¹ Regardless of what [results were observed], it appears that having a pCR or having a good response to neoadjuvant treatment dictates how they do afterward. Having a clinical trial that has that combined neoadjuvant and adjuvant data is important. I will start to look for patients who might benefit from [pembrolizumab] in this setting, and I will start to use this regimen once I find a patient.

What was your biggest takeaway from the discussion with your colleagues today?

I enjoyed having my 2 esteemed colleagues here. Sai-Hong Ignatius Ou, MD, PhD, is my colleague and mentor, and he’s a thoracic oncology colleague. I also had Janellen Smith, MD, who is our dermatology oncologist. We all work together; Dr Ou and I share a clinic 3 days a week, and with Dr Smith, I share a clinic 2 days a week. We work side by side, and we share a lot of patients. There are patients [whom], if I have questions, I can ask Dr Ou [about]. There are random rashes that occur that I take a picture of, and I’ll just send it to Dr Smith and say, “Can you please see the patient? What should I do in the meantime?” We were able to share what we do in the clinic during our discussion. The key message, especially for dermatologic adverse effects [AEs], is that for the most part, you can continue patients on their cancer treatment [regimen] while comanaging patients with the dermatology teams. It’s important to send the message out that, by working together, we can have patients stay on treatment for a longer period with a better quality of life.

Are you currently involved in any ongoing research?

I am lucky to be in an institution where I have the backup and support to be able to open many clinical trials, including first-in-human and early-phase studies. For the topics that we talked about today [regarding] amivantamab, we are opening the phase 1 PALOMA trial [NCT04606381], which is basically [administering] subcutaneous amivantamab.⁵ It will be the first time [that I acquire] experience with that version of amivantamab. I’m excited because from preliminary data that I’ve seen, I’ve been told that the AE rates have decreased, and that’s important for patients. For my investigator-initiated [study], I am trying to identify the correlation between the gut microbiome and the responses as well as the severity and prevalence of AEs in patients who are receiving care for their lung cancer.

I know there’s a lot of data that are coming out in the melanoma field regarding immunotherapy and gut microbiome, but what I want to see in this study that I am opening as an investigator-initiated study is [whether] there [are] any differences in the microbiome, for example, [for] people who have more diarrhea with a tyrosine kinase inhibitor. By defining the changes that occur with treatment, we may be able to intervene early and prevent or manage these AEs.

References

1. Fernando HC, Yang J, Ferraro GL, Keller SM. Randomized, double-blind phase 3 study evaluating neoadjuvant platinum-based chemotherapy with perioperative pembrolizumab or placebo in resectable stage IIB or IIIA NSCLC: KEYNOTE-671. J Clin Oncol. 2018;36(suppl 15):TPS8583. doi:10.1200/jco.2018.36.15_suppl.tps8583
2. Forde PM, Spicer J, Lu S, et al; CheckMate 816 Investigators. Neoadjuvant nivolumab plus chemotherapy in resectable lung cancer. N Engl J Med. 2022;386(21):1973-1985. doi:10.1056/nejmoa2202170
3. O’Brien M, Paz-Ares L, Marreaud S, et al; EORTC-1416-LCG/ETOP 8-15 – PEARLS/KEYNOTE-091 Investigators. Pembrolizumab versus placebo as adjuvant therapy for completely resected stage IB-IIIA non-small-cell lung cancer (PEARLS/KEYNOTE-091): an interim analysis of a randomised, triple-blind, phase 3 trial. Lancet Oncol. 2022;23(10):1274-1286. doi:10.1016/s1470-2045(22)00518-6
4. Felip E, Altorki N, Zhou C, et al. Overall survival with adjuvant atezolizumab after chemotherapy in resected stage II-IIIA non-small-cell lung cancer (IMpower010): a randomised, multicentre, open-label, phase III trial. Ann Oncol. 2023;34(10):907-919. doi:10.1016/j.annonc.2023.07.001
5. Minchom AR, Krebs MG, Cho BC, et al. Subcutaneous amivantamab (ami) in patients (pts) with advanced solid malignancies: the PALOMA study—updated safety and identification of the recommended phase 2 dose. J Clin Oncol. 2023;41(suppl 16):9126. doi:10.1200/jco.2023.41.16_suppl.9126