Considerations when using adjuvant chemotherapy and osimertinib with NSCLC

Case overview

An otherwise healthy 60-year-old Caucasian woman showed an unproductive cough. She was a former smoker who quit eight years ago (13 pack years). Her ECOG performance score was 0, her blood pressure was 120/93, her heart rate was 75, her obesity index was 22, and her lungs could be auscultated on both sides. All test results were within normal limits. Chest X-ray showed a 5.5 cm right mass in the upper right lobe of the lung, and CT chest / abdominal scan showed a 5.5 x 5.1 cm lobular mass in the upper right lobe.

A biopsy of the upper right lobe revealed a thyroid transcription factor 1-positive adenocarcinoma consistent with non-small cell lung cancer (NSCLC). The results of positron emission tomography were negative for lymph node metastases or distant metastases. Brain MRI was negative and respiratory function testing was normal.

The patient underwent right upper lobectomy without complications. Pathology showed that she had a 5.5 cm tumor with a negative margin, negative lymph nodes, and pathological stage IIB * (pT3N0M0) lung adenocarcinoma. Her ECOG performance status is now 1.

Discussion question:

• What is the role of adjuvant chemotherapy in your practice? What are the goals of treatment?
• Which regimen do you usually use?
• Which parameters are important in deciding whether to use adjuvant systemic therapy after resection? Do you consider tumor size, number of metastatic lymph nodes, or histologically low-risk features?

MERIN STEPHEN, MD: I just go to NCCN [National Comprehensive Cancer Network] Run the guidelines and the latest data, [considering] Typical goal of adjuvant therapy. If it is after their chemoradiotherapy, then if they are willing to accept the toxicity of additional chemotherapy, then we go that way. I offer it to those who are qualified and willing.

I’m used to it because lymph node metastasis-positive illness is what I see more as an indication for typical patients in need of adjuvant therapy.Need to look back on patients with large tumors [as to] A person who is exactly qualified.

Aaron E. Lisberg, MD: Which regimen do you usually use for adjuvant chemotherapy?

Stephan: It depends on adenocarcinoma vs. squamous cell carcinoma [histology].. It was more immunotherapy and chemotherapy because I haven’t used targeted therapy yet.

NIHAL ABDULLA, MD: I comply with the NCCN guidelines, so I try to give adjuvant chemotherapy to those who are qualified and stage IB. [disease] that’s all.¹ The goal of treatment is to provide recommended treatment and improve overall survival.

When I’m on treatment, I’m mainly trying to get cisplatin compared to carboplatin.Then maybe I would consider pemetrexed [Alimta].. Alternatively, consider taxane-based combination therapy for patients with squamous cell carcinoma. And I’ve recently been testing patients for mutations in an adjuvant therapy setting and trying to order next-generation sequencing myself.

Liseberg: When deciding for or against adjuvant chemotherapy, which are the most important factors in making those decisions?

Abdullah: The number one factor is the condition of the lymph nodes. There is confusion about the size of the tumor.If it’s less than 4 cm, I’m trying [consider] These high-risk functions such as pleural invasion and lymphatic invasion. Whenever there are patients who do not meet the criteria, it is best to discuss the case with the oncology committee and the pathologist. From time to time we learn that there are more features that guide our treatment. I learned a lot at the Oncology Committee meeting to discuss these cases, especially borderline cases.

Liseberg: Are you discussing most early NSCLC patients on the tumor board, or are you only discussing patients on the fence?

Abdullah: In our practice we try to do all of them.

Liseberg: We always know that discussions about adjuvant therapy can go in different directions depending on the patient. How do you usually approach that discussion?

Abdullah: Whenever there is a patient or is discussing adjuvant therapy, a graph available online is displayed to indicate an increased risk of recurrence.Even sick patients [is treated with] Excision, [the risk rate comes] From 50% to 60%.² Most patients have relapsed. That is the main driving force.

I’ll show you the graph [and say]”You can still have a chance of recurrence, but at least you will reduce the chances.” For some patients, I had a problem that went into too much detail.

Liseberg: Dr. Sam Ye, what do you think about this?

SAM YEH, MD: All factors are important: tumor size, node [status] Very important — hilar nodes are positive and nodes are negative. If they are node negative, I think of other high-risk features. They are all important: age, performance status, and potential toxicity. The more elements you add together, the more important they become.

I think it’s controversial when the tumor size is 4 cm and the lymph nodes are negative. Are there any benefits of chemotherapy? [then] Are you using cisplatin or carboplatin?If they have EGFR Are you using mutations, EGFR tyrosine kinase inhibitors and immunotherapy? For N1 node positive patients, I’m not very clear [chemotherapy benefit]..

Liseberg: Which chemotherapy backbone do you usually use?

YEH: I use platinum-based chemotherapy because it is based on all research. Cisplatin is the way to go. Pemetrexed is what I use for adenocarcinoma. Then, for squamous cell carcinoma, you probably choose docetaxel.

Liseberg: In stage IIB, where the margin is negative N0 or N1 disease, NCCN guidelines indicate chemotherapy and osimertinib [Tagrisso] As a Category 1 recommendation.¹

Case update:

After resection, the patient receives 4-cycle adjuvant chemotherapy with cisplatin and pemetrexed. Her ECOG performance status is 1.Molecular test EGFR Exxon 19 removed.

Discussion question:

• What is your reaction to the data from the ADAURA trial (NCT02511106) for the adjuvant ossimertinib?

Liseberg: How is your reaction to the ADAURA data?

SAI-HONG OU, MD: ADAURA is changing the paradigm.Result is [published in] the New England Journal of Medicine..³ this is [led to approval of adjuvant osimertinib] From Stage IB to IIIA NSCLC by FDA [for patients with EGFR exon 19 deletions or exon 21 L858R]..^Four There is no problem. I am a true believer. [question] Results of lung cancer screening for non-smokers.^4,5 One thing [individuals] Is that you do not screen because we cannot find [which] Patients with lung cancer are smokers, but that is not true. Hopefully in 2022, we will present some data, a meta-analysis.

However, if the disease is detected early, osimertinib improves disease-free survival. [DFS]There is no doubt about it.

Free stratification factors did not include adjuvant chemotherapy, whether or not the patient was stratified with adjuvant chemotherapy.Paper Chest Oncology Journal Is essentially [that patients in ADAURA who received] Adjuvant chemotherapy [before receiving osimertinib] DFS had no merit [versus those who did not receive adjuvant chemotherapy before osimertinib]..⁶ It just checks the absolute number for each stage. You can plot bar charts, but they are the same.

It is a change in practice, which points the way to other adjuvant therapies, EGFR However ALK, ROS1, NTRK, MET Exxon 14 [and other targets].. It’s huge. You can see DFS, [though] 3 or 5 years [or] Indefinite is the key.

Liseberg: Data from Chest Oncology Journal It is very interesting. Indeed, from a quality of life and toxicity perspective, I think that’s an unanswered question, as we all want to avoid adjuvant chemotherapy if possible. EGFR-Positive patients. I don’t know if the data is there and I think it’s a subgroup analysis, but it’s very interesting.

_References

_{1. NCCN. Clinical practice guidelines in oncology. Non-small cell lung cancer, version 3.2022. Accessed on May 26, 2022. https: //bit.ly/3NC4OI1}

_{2. Recurrence after surgery in patients with Uramoto H and Tanaka F. NSCLC. Transl Lung Cancer Res. 2014; 3 (4): 242-249. doi: 10.3978 / j.issn.2218-6751.2013.12.05}

_{3. The FDA approves osimertinib as an adjunct therapy for non-small cell lung cancer with EGFR mutations. FDA. December 18, 2022. Accessed on May 26, 2022. https: //bit.ly/3sYuSp8}

_{4. Wu YL, Tsuboi M, He J, et al; ADAURA Investigators. Osimertinib in resected EGFR mutant non-small cell lung cancer. N Engl J Med. 2020; 383 (18): 1711-1723. doi: 10.1056 / NEJMoa2027071}

_{5. Final Recommendation Statement Lung Cancer: Screening. United States Preventive Services Task Force. March 9, 2021. Accessed on May 26, 2022. https: //bit.ly/3NRziG2}

_{6. Wu YL, John T, Grohe C, etc. Postoperative Chemotherapy Use and ADAURA Results: Osimertinib as Adjuvant Therapy for Resected EGFR Mutant NSCLC. JThorac Oncol. 2022; 17 (3): 423-433. Doi: 10.1016 / j.jtho.2021.10.014}