The importance of molecular testing before adjuvant therapy for NSCLC

During a case-based roundtable on targeted oncology, Edward S. Kim, MD, MBA, discussed adjuvant therapy options and the use of molecular testing in patients with early-stage non-small cell lung cancer. This is the first of 2 articles based on this event.

DISCUSSION QUESTIONS:

  • What are the challenges and barriers to molecular testing for non-small cell lung cancer (NSCLC) patients?
  • Who on the multidisciplinary team orders molecular tests?
  • What tests are requested at your institution/office?

EDWARD KIM, MD, MBA: What do you see as problems or challenges in taking the test? Who in the multidisciplinary team orders molecular tests and which tests are ordered?

RAYMOND LOBINS, DO: One of the problems we have is with these early cancers, we often don’t see them until after they’ve already had the first surgery. Many times they go to the pulmonologist, and the pulmonologist sees their small tumor. And many times, they don’t even do a biopsy. They’ll send them to the surgical oncologist, who does the biopsy and then switches to a lobectomy if it’s cancerous.

Kim: It can definitely happen. If you are in a situation where the pulmonologist sees them and then [they go] straight to a surgeon, sometimes the oncologist is [the last] know. It becomes challenging so I agree with that. Who orders the tests? Are all of you oncologists for your practice?

WOLVES: Yes.

LIN HAO, MD: In my practice, we develop a reflex [testing protocol] for all tumors larger than 3 cm.… For disease greater than stage IB, we reflect to [molecular testing]. [First, we need] mutation status for adjuvant treatment. Sometimes, for example, if a patient has a 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 start moving to 3 cm [tumors] Right now.

Most of the time, we have no problems with insurance. Occasionally they have some questions, but these [patients] didn’t have any big problems. FoundationOne called us. They only charged $100 if insurance didn’t cover it [their test].

Kim: Some of the academic centers have done that, where they do reflex tests on everybody with lung cancer. Besides the big genomic test, is anyone else running small panels? you are always testing EGFR [only]?

GETINET AYALEV, MD: we tested for EGFR in early-stage lung cancer. with 3 cm [or larger]we tend to order EGFR just because of the adjuvant data. Medical oncology orders these tests. I don’t see any barriers or impediments, nor any problems with insurance. 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 broad panel of state-of-the-art 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: That sounds pretty consistent [to others]?

NADINE MIKHAEEL, MD: We do this in our patients. I usually do the whole panel because it doesn’t make a difference how much goes [cost]. I would say if I’m in a hurry I can do what EGFR by itself to get an answer on this quickly, but do the rest. Oncology orders the tests and I order them based on the information I get from the pathologist and whether the patient is eligible for treatment or not.

VISHAL RANA, MD: I agree. Like most of [participants], now we do NGS. It’s a more effective use of tissue and it’s cheaper to run NGS and get all the results instead of individual tests; this has been the standard at our institution.

DISCUSSION QUESTIONS

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

Kim: For [participants] who do not wish to treat patients with tumors larger than 4 cm with adjuvant systemic therapy, it is primarily lymph node status or is avoiding this risk-benefit [issue]?

WOLVES: Part of it is if they don’t have positive lymph nodes, the data isn’t as strong.1 The other part is that in training they always suggest you use cisplatin. And when you look at the data with the patient, I would say almost half the time the patient says no, because even the last meta-analysis didn’t show as much benefit.

Kim: Yes, they can also feel like they’ve been healed from the surgery, so it can be challenging there sometimes. [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 generally lean towards adjuvant chemotherapy, even in the early stages. I normally use a lot of cisplatin plus pemetrexed [Alimta]. In recent months, I started using more neoadjuvant nivolumab [Opdivo] for 3 cycles with platinum doublet. I would be curious what others thought about it too.

I started using more neoadjuvant immunotherapy and am just trying to get them through the 4 cycles; it is relatively doable with regard to toxicity. But I agree that many patients don’t want to go through chemotherapy with all the adverse events. But I often show them the recurrence risk chart. Even for early-stage disease, they think they are “cured”. They are often systemic diseases.

POWERFUL, MD: I simply use cisplatin or cisplatin/gemcitabine in most of my adjuvant patients. In terms of what Dr. George said, if these patients have a EGFR mutation, would you use chemoimmunotherapy before surgery?

Kim: We would avoid immunotherapy if they had a EGFR mutation. And it’s good to try this out if you’re thinking [about] neoadjuvant therapy. Would you like to test for EGFR. It is also recommended to test for ALK and ROS1 too, although the data isn’t as strong there.two But absolutely, before you give any neoadjuvant systemic treatment, I would make sure that you have the biomarkers done.

I still remember 2004 when we finally got the definitive studies and we thought we should use adjuvant chemotherapy. We [now] there are some others [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 which stage is right [to use each].

References:

1. Pignon JP, Tribodet H, Scagliotti GV, et al. Evaluation of pulmonary adjuvant cisplatin: 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 randomized, multicentre, open-label phase 3 study. Lancet. 2021;398(10308):1344-1357. doi:10.1016/S0140-6736(21)02098-5

The importance of molecular testing before adjuvant therapy for NSCLC

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