Excluding Inappropriate Treatment Approaches in NSCLC

Mark A. Socinski, MD:In stage III disease, to reiterate, even though many patients are tested for various molecular markers, as well as PD-L1 [programmed death-ligand 1], we don’t know exactly how to use those. So, in my practice, I’m agnostic to those outcomes, even though I can tell you that in our system, at my cancer institute, many stage III patients do undergo testing for PD-L1 as well as molecular testing. If the plan is to do chemoradiation in stage III patients, then I don’t know how to use the information regarding the molecular markers in PD-L1 status to change anything that I would do. I think the PACIFIC data, which included all patients regardless of PD-L1 status, show that the benefit you see from checkpoint inhibition has to be assumed for all patients. And we don’t have enough granularity and information from the PACIFIC trial to say that you should exclude this patient or that patient, no. All patients should be assumed to get benefit.

In this particular patient, because he had multistation bulky N2 disease that was proven at the time of EBUS [endobronchial ultrasonography], I don’t think that surgery plays a role. We have at least 2 randomized trials in patients like this that have evaluated the role of surgery, and neither one of those trials has shown a benefit to the addition of surgery versus chemoradiation.

So, I do not think that surgery plays a role in patients with bulky multistation N2 disease; those patients are best managed with chemoradiation. Because many patients feel, “Well, if I can’t have surgery, I can’t be cured,” I say, “No, that’s not the case. Surgery is not necessarily a part of your curative strategy.” We know that we cure patients with chemoradiation, and we know that with the addition of checkpoint inhibition following concurrent chemoradiation, we actually cure more patients.

One of the questions that PACIFIC has raised is should we rethink the issue of resection knowing what we know about the use of checkpoint inhibition? Based on the PACIFIC trial in those patients who may be borderline candidates for resectability, would you defer to the PACIFIC approach rather than integrate surgery? I don’t know. My bias is that the vast majority of stage III patients are unresectable, or even though they are technically resectable, we don’t know that resection adds to their long-term survival. We do know that the addition of checkpoint inhibition after chemoradiation improves their long-term survival. We don’t know that surgery does that.

So I think that in my centers or institutions where there’s a strong surgical bias, I would advise them to rethink that. My bias for years in this disease setting is that surgery does not play a major role in the management of these patients. And, if surgery is playing a major role, then I think you need to consider the PACIFIC results and reassess what you’re doing in this particular setting. Again, surgery has never been demonstrated to improve survival. Checkpoint inhibition has been after chemoradiation, and we don’t know how or if we should do checkpoint inhibition following surgery. Those are trials that are ongoing, vitally important trials. If you have the ability to accrue a patient to the trial, you should, so that we get an answer quicker. But, right now in the surgical setting, we don’t know how to use the checkpoint inhibitors.

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