The Importance of Molecular Testing Before Adjuvant Therapy for NSCLC

Edward S. Kim, MD, MBA (Moderator)
Physician-in-Chief, City of Hope Orange County
Vice Physician-in-Chief, City of Hope National Medical Center
Newport Beach, CA

DISCUSSION QUESTIONS:

• What are the challenges and barriers to molecular testing for patients with non–small cell lung cancer (NSCLC)?​
• Who on the multidisciplinary team orders molecular testing?​
• What tests are ordered at your institution/practice?

EDWARD KIM, MD, MBA: What do you see as issues or challenges to getting testing done? Who on the multidisciplinary team orders the molecular testing and what tests are ordered?

RAYMOND LOBINS, DO: One of the problems that we have is on these early cancers, a lot of times we don't see them until after they've already had their first surgery. A lot of times they'll go to pulmonology, and pulmonology will see their small tumor. And a lot of times, they don't even biopsy those. They'll send them to the surgical oncologist, who does the biopsy and then switches it over to a lobectomy if it's cancerous.

KIM: That definitely can happen. If you're in a situation where the pulmonologist sees them and then [they go] straight to a surgeon, sometimes the medical oncologist is [the last] to know. That does get challenging, and so I agree with that. Who orders the testing? Is it you all, the medical oncologists, for your practice?

LOBINS: Yes.

LIN HAO, MD: In my practice, we developed a reflex [testing protocol] for all the tumors larger than 3 cm.… For higher than stage IB disease, we reflex to [molecular testing]. [First, we need] mutation status for adjuvant treatment. Sometimes, for example, if a patient has an EGFR mutation, we can use osimertinib [Tagrisso]. I'm more likely to…discuss more [with the patient] about adjuvant chemotherapy. I used to do [testing for tumors larger than] 4 cm but with some discussion for stage IB disease, 3 cm to 4 cm, we started to move to 3 cm [tumors] at this time.

Most of the time, we don't have problem with the insurance. Occasionally, they have some questions but these [patients] didn't have big problems. FoundationOne has called us. They only charged $100 if insurance didn’t cover [their test].

KIM: Some of the academic centers have done that, where they do reflex testing on everyone with lung cancer. Other than the big genomic test, is anybody else running small panels? Are you ever testing EGFR [only]?

GETINET AYALEW, MD: We do test for EGFR in early-stage lung cancer. With 3 cm [or larger], we tend to order EGFR only because of the adjuvant data. Medical oncology orders those tests. I don't see any barrier or hindrance, or any problems with insurance either. We also…have a weekly lung cancer tumor board and most thoracic oncologists and medical oncologists are encouraged to use molecular testing. We use a wide panel next-generation sequencing [NGS] for patients with stage IV disease.

KIM: Which one do you use for patients with stage IV disease?

AYALEW: Typically, Tempus NGS for stage IV NSCLC to look for all actionable mutations.

KIM: Does that sound pretty consistent [to others]?

NADINE MIKHAEEL, MD: We do it on our patients. I usually do the whole panel because it doesn't make a difference in how much it will [cost]. I would say that if I'm in a rush, I may do the EGFR by itself to get an answer on that quickly, but then get the rest done. Oncology orders the testing and I order it based on the information I get from the pathologist, and if the patient is eligible for treatment or not.

VISHAL RANA, MD: I agree. Like most of the [participants], we now do NGS. It's a more effective utilization of tissue and it's cheaper to run the NGS and get all the results rather than single tests; that's been the standard at our institution.

DISCUSSION QUESTIONS

• What is the role of adjuvant chemotherapy in your practice? What are the treatment goals?​
• Which regimen(s) do you typically employ?​

KIM: For [participants] who are not wanting to treat patients who had tumors greater than 4 cm with adjuvant systemic therapy, is it mostly the lymph node status or is it avoiding that risk-benefit [issue]?

LOBINS: Part of it is, if they don't have positive lymph nodes, the data are not quite as strong.¹ The other part of it is, in the training, they always suggest that you use cisplatin. And when you go over the data with the patient, I would say almost half the time the patient says no, because even the latest meta-analysis didn't show that much of a benefit.

KIM: Yes, they can also feel like were cured from the surgery, so sometimes it can be challenging there. [For those who would use adjuvant therapy], what would you normally use for these patients?

BENJAMIN GEORGE, MD: I think we all know that even stage I lung cancer has a high recurrence rate, so I usually lean towards adjuvant chemotherapy, even in the earlier stages. I typically use a lot of cisplatin plus pemetrexed [Alimta]. In the last couple of months, I started using more neoadjuvant nivolumab [Opdivo] for 3 cycles with platinum doublet. I’d be curious about what others thought about that, too.

I started to use more neoadjuvant immunotherapy and I am just trying to get them through the 4 cycles; it is relatively doable as far as toxicity. But I do agree that a lot of patients don't want to go through chemotherapy with all the adverse events. But a lot of times I'll show them the graph of the risk of recurrence. Even for earliest-stage disease, they think they're “cured”. Oftentimes, these are systemic diseases.

IKE ONWERE, MD: I simply use cisplatin or cisplatin/gemcitabine on most of my adjuvant patients. In terms of what Dr George said, if these patients have an EGFR mutation, would you use chemoimmunotherapy prior to surgery?

KIM: We would avoid the immunotherapy if they had an EGFR mutation. And it's good to test for that if you're thinking [about] neoadjuvant therapy. You'd want to test for EGFR. It is also recommended to do testing for ALK and ROS1 as well, though the data are not as strong there.² But absolutely, before administering any neoadjuvant systemic treatment, I would make sure you have the biomarkers done.

I still remember in 2004 when we finally got definitive studies and we thought we should use adjuvant chemotherapy. We [now] have a couple of other [regimens] in the arsenal, and now as many of you have alluded to, we have data for neoadjuvant therapy. We not only have [data supporting systemic therapy] on the adjuvant side, we have immunotherapy on the adjuvant side.³

We have EGFR-targeted therapy on the adjuvant side and we have immunotherapy on the neoadjuvant side. So, it's getting complicated fast and here we are still debating what is the right stage [to use each].

_References:

_{1. Pignon JP, Tribodet H, Scagliotti GV, et al. Lung adjuvant cisplatin evaluation: a pooled analysis by the LACE Collaborative Group. J Clin Oncol. 2008;26(21):3552-3559. doi:10.1200/JCO.2007.13.9030}

_{2. NCCN. Clinical practice guidelines in oncology. Non–small cell lung cancer, version 1.2023. Accessed January 23, 2023. https://bit.ly/3GYx3Pz}

_{3. Felip E, Altorki N, Zhou C, et al. Adjuvant atezolizumab after adjuvant chemotherapy in resected stage IB-IIIA non-small-cell lung cancer (IMpower010): a randomised, multicentre, open-label, phase 3 trial. Lancet. 2021;398(10308):1344-1357. doi:10.1016/S0140-6736(21)02098-5}