Part 1: Using Adjuvant Chemotherapy for EGFR-Positive NSCLC

Matthew A. Gubens, MD, MS (Moderator)

Thoracic Oncologist

UCSF Thoracic Surgery and Oncology Clinic

Helen Diller Family Comprehensive Cancer Center

UCSF Health

San Francisco, CA

DISCUSSION QUESTIONS

• What is the role of adjuvant chemotherapy in your practice? What are the treatment goals?
• Which regimen(s) do you typically employ?
• Which parameters are important when deciding on whether to use adjuvant systemic therapy post resection?

MATTHEW GUBENS, MD, MS: Do you talk about goals with your patients? Are you giving numbers in your clinic? How is that conversation going?

MUJAHID RIZVI, MD: You are looking at the risk factors or the poor risk features—age, performance status, size of the tumor, all of those things—giving the patient the numbers as well. A lot of times if they are older, in my experience, when you give them the numbers, if the tumor is on the smaller side, a lot of them will say no [to adjuvant therapy]. But that is what usually happens.

TIMUR MITIN, MD, PHD: There is also an important component of what the surgeons have told the patient. If the surgeon said they got all [of the cancer], it is going to convince the patient [not] to get any other additional treatments. If the surgeon said that the tumor that has a tendency to recur, and they need to talk to a medical oncologist to reduce those chances, usually that is a better setup for further discussions.

GUBENS: That is an excellent point, especially when we are talking about smaller, node-positive tumors. They are not sure that some of those patients get to our clinic; the surgeon is confident that they got it all even if they are evidence based. Maybe it is just not foremost on their mind to think that a 4.1-cm tumor needs much more attention than surveillance, so a good point. There is priming being done all around the clinic.

What kind of regimens are people using for patients with adenocarcinoma? If you are deploying an adjuvant chemotherapy for a patient with stage IIB adenocarcinoma, what are you using?

MICHAEL HARRIS, MD: I tend to use pemetrexed [Alimta] and carboplatin for a patient with adenocarcinoma. I tell the patient that there are some options including taxanes, but when I describe neuropathy as being frequent accompanying it, that in a potentially curable situation, neuropathy can be long lasting or permanent, usually I gravitate back toward pemetrexed.

GUBENS: Do you want to weigh in on that cisplatin vs carboplatin age-old debate? I feel like there have been debates of the lectern since I was young. Are physicians reaching for cisplatin and are you talking about both with patients?

HARRIS: Usually, I will bring up cisplatin as being the more curative by 3% or 4%. I used to be more of a proponent of Anthony Greco, MD; he says for these patients, despite the small benefit of cisplatin over carboplatin, the quality-of-life issues are probably significant as well. So I will usually ask the patient. But if they are an elderly patient and they have impaired kidney disease or a creatinine elevation of any kind, it is difficult for me to push very hard with cisplatin.

RACHNA ANAND, DO: I also use a carboplatin-based doublet in most patients unless they are a young patient, early 60s or late 50s, who does not have too many medical conditions. In that case, I stick to a cisplatin-based doublet.

RIZVI: I try to give cisplatin as much as possible. I am usually very generous with fluids in the week they get cisplatin to keep their kidneys [healthy].

DIANA SUPERFIN, MD: I try to do cisplatin. I have to sometimes give hydration. Sometimes I may dose-reduce cisplatin, 20% on the first cycle…then if they tolerate it well, I will go up to the full dose on the second. If the patient cannot do that for whatever reason—renal function or a lot of comorbidities—I will do carboplatin.

GUBENS: There is a gradient, too. The older the patient, the more comorbidities, the quicker you are going to jump off this cisplatin wagon or accept that you need to go to carboplatin. I think that that is fair.

The National Comprehensive Cancer Network guidelines have a list of relative factors aside from the strict staging that might influence whether or not you choose chemotherapy.¹ I think the most provocative one is probably the tumor size. Are there factors that make you treat someone with a tumor under 4 cm without nodes? That is a population for which there is not randomized control data favoring overall survival [OS] benefit.

HARRIS: This was looked at in the CALGB 9633 study [NCT00002852]; it was subset analysis [looking at] what we do for something 3.9 cm vs 4.1 cm.² I think you have to use some judgment as well. I [am not sure] about the strength of the statistics in that subset analysis, but it is suggestive benefit if it is greater than 4 cm. So I usually tell the patients that.

GUBENS: Fair enough. Dr Superfin, you brought up DetermaRx. Are you using it in that setting?

SUPERFIN: Yes, I use DetermaRx in adenocarcinomas stage IA to IIA. Mostly IA because IB and IIA, [we’re usually] already giving chemotherapy. That is a gray area. In the high- or intermediate-risk patients, I offer chemotherapy. [DetermaRx] does give me EGFR results, but even with EGFR-positive disease, I cannot use [chemotherapy in] IA, because the study was done in IB or higher. I have used it in a couple of patients already. I give cisplatin-based doublets if I can.

_References:

_{1. NCCN. Clinical Practice Guidelines in Oncology. Non-small cell lung cancer, version 2.2022. Accessed March 8, 2022. https://bit.ly/33qNCn6}

_{2. Strauss GM, Herndon JE 2nd, Maddaus MA, et al. Adjuvant paclitaxel plus carboplatin compared with observation in stage IB non-small-cell lung cancer: CALGB 9633 with the Cancer and Leukemia Group B, Radiation Therapy Oncology Group, and North Central Cancer Treatment Group Study Groups. J Clin Oncol. 2008;26(31):5043-5051. Doi:10.1200/JCO.2008.16.4855}