NSCLC: Take-Home Messages and Unmet Needs

Mark A. Socinski, MD:One of the things that I think is important in patients with stage III non—small cell lung cancer [NSCLC] is that you have a multidisciplinary team that evaluates the patient at the time of diagnosis, that there’s an evaluation by a medical, radiation, and thoracic surgeon. And I think those 3 disciplines should define is this patient a potentially resectable patient. I think one of the great mistakes that oncologists make in this setting is saying, “Well, it doesn’t look resectable now, but let’s give some chemotherapy or some chemoradiation, neoadjuvant therapy, and then reassess them for surgery.” That is a dangerous and irresponsible strategy, in my opinion.

We don’t have good tools in terms of trying to figure out who are the patients that should go on for surgery and who are the patients that should get definitive chemoradiation. Delaying the decision often leads to a delay in treatment. I mentioned before that one of the important things is getting patients through treatment on time without interruption. And these things that you do to try to reassess patients during treatment without good parameters, in terms of how to judge one way or the other, can lead to significant delays.

So I think you need to decide, is a patient going to consider surgery or is surgery going to be part of the patient’s treatment before you start any treatment? If surgery is a part of their treatment, then clearly they need to have neoadjuvant treatment. And I think that neoadjuvant treatment should be chemotherapy with radiation because those are the most compelling data. But I would say in my practice, and at our institution, for the vast majority of stage III patients, we do not consider surgery as part of their treatment.

For the community oncologist, I think it’s important to make sure you have a multidisciplinary team—medical oncologist, radiation oncologist, thoracic surgeon—that is evaluating stage III patients, that you adequately and diligently stage patients. You shouldn’t assume that an enlarged lymph node, even if it’s PET [positron-emission tomography]-positive, is cancer. It should be biopsied to prove that it’s N2 or N3 disease, depending on where it is. So accurate staging is an important message, and discussing it amongst the specialties to get a plan.

Most often in stage III disease, that plan is going to be chemoradiation. Again, have a team of medical and radiation oncologists and their staff support the patient through it, get the patient through from point A to point B without a break, manage their toxicities appropriately, reassess them afterwards, and get them to immunotherapy if they’re a candidate for that because of the potential you have for overall survival in these particular patients.

Regarding unmet needs, there are many. We don’t cure everybody. How do we improve that cure rate? What other immune checkpoint inhibitors should we think about incorporating to improve the benefit? Can we build on the PACIFIC trial to make the outcomes even better? We know that much of non—small cell is a molecularly complex disease. We have a number of oncogenic drivers:EGFRmutations,ALKtranslocations, and others. What’s the role of targeted therapy in those particular subsets in stage III disease? Those are as of yet undefined. So I think that there’s a lot of work ahead to be done. Many clinical trials are ongoing and addressing many of the issues that I just discussed. But that’s where we need to go in stage III disease in the future.

Transcript edited for clarity.

Case: A 52-Year-Old Male With Stage IIIA NSCLC

Initial presentation

• A 52-year-old man presented with a 15-lb weight loss and worsening dyspnea
• PMH: HTN
• SH: Computer programmer; Smoked a pack/day for 30 years; Quit smoking 2 years ago; Married with 4 kids
• PE: Unremarkable

Clinical workup

• Imaging:
  • Initial CT showed a 5-cm left upper lobe mass with aortopulmonary window and left paratracheal adenopathy measuring up to 2.5 cm
  • Subsequent PET scan showed activity in the left upper lobe mass and all nodal areas
  • No extrathoracic disease was identified
  • MRI showed no brain metastases
• Mediastinal sampling: EBUS was performed and documented squamous carcinoma in the left paratracheal lymph nodes
• Staging: T2N2M0
• ECOG PS 1
• Multidisciplinary tumor board deemed his tumor unresectable due to multistation N2 disease

Treatment

• Concurrent cisplatin/etoposide with external-beam radiotherapy
• Repeat CT 4 weeks after completion of concurrent chemoradiotherapy showed a PR with no new sites of disease