Locally Advanced NSCLC: Treating With I-O

Hossein Borghaei, DO, MS:I think patients with unresectable, locally advanced disease, stage III disease, make up probably the most heterogeneous patient population we see in the world of lung cancer treatment. At our institution, these patients are discussed extensively at our multidisciplinary tumor boards. Our surgeons, our radiation oncologists, our radiologists, our medical oncologists, everybody, pulmonary, participate in these discussions because this is a unique group of patients as far as I’m concerned. They could have more comorbidities, either as a result of medical history or by virtue of having locally advanced disease. Some of these patients are really symptomatic, and I think this is 1 area where we do really absolutely need a multidisciplinary approach to the management of these patients. It is a rare patient with locally advanced disease, at least at my institution, who is not followed by a pulmonologist and is not closely monitored by medical oncology, radiation oncology, all of those.

And I think it is that multidisciplinary approach that makes aggressive treatments like chemotherapy radiation followed by durvalumab possible. Again, these patients could have numerous toxicities and issues that require a close management and follow-up. So to me, durvalumab is an enhancement over and above what we’ve been doing. I think it is, for me, the standard of care. Again, I will discuss and offer it to most of my patients who I think are eligible for it. But I would not sort of go on my own and treat these patients without having the multidisciplinary team involved to help me manage all the aspects of the care of these patients.

PD-L1 [programmed death-ligand 1] in stage III locally advanced patients has become a little bit controversial. Let’s take it 1 by 1 and sort of go over the issues. I’ve had these discussions with my colleagues, and people are either on 1 side or the other of the argument. So why is there a controversy? In an unplanned, subgroup analysis requested by medical authorities in other countries, the investigators for the PACIFIC study went back and looked at the impact of PD-L1 expression on the clinical utility of durvalumab after chemotherapy radiation. In this unplanned subgroup analysis, and I again have to emphasize that this was an unplanned subgroup analysis, patients with PD-L1 expression, basically less than 1%, did not seem to have the same overall survival benefit from durvalumab that patients did with higher levels of PD-L1 expression.

This has raised the question of whether we should offer durvalumab, which again, with a checkpoint inhibitor could have potential toxicities to a patient population, meaning those less than PD-L1, less than 1%, who could not benefit. I think it’s a valid question, but I hate to make a decision based on an unplanned subgroup analysis. The reason I say that is because in the intent-to-treat patient population, meaning all comers, the study is clearly positive for the use of durvalumab following chemotherapy radiation.

I think for those patients who have a PD-L1 expression that is less than 1%, the medical oncologists who would administer the durvalumab should have a very clear, open discussion about the data with the patient to let the patient know that, based on the subgroup analysis, there is a possibility that they would not benefit from the use of durvalumab. Not only that, but also the fact that a) they could be responsible for some co-pay, and b) that they could suffer an immune-related adverse event because it is a checkpoint inhibitor.

I think for the well-informed patient, discussing all the caveats of all the subgroup analysis, I am comfortable with offering durvalumab at this point to that group of patients who walk into my clinic. So I do check PD-L1 expression, and I use it as a point of discussion with my patients. In the case that we have here, this patient has PD-L1 expression that’s well over 1%, so I don’t think there is much of a discussion in this case. But in the case of someone with less than 1% PD-L1 expression, I think that does deserve a discussion with the patient.

And I think this is an area where we need additional studies to really, in a well-designed randomized fashion, try to figure out if PD-L1-negative patients truly are not going to benefit from the use of durvalumab or not. So again, I think it’s a little bit controversial. We do need more data. But I tend not to make those kinds of decisions without a clear discussion with the patient when the decision is based on a subgroup analysis that was not planned.

Transcript edited for clarity.

Case: A 72-Year-Old Female With Stage IIIB NSCLC

Initial presentation

• A 72-year-old woman presented with a 17-lb weight loss and dyspnea
• PMH: HTN and hyperlipidemia
• PSH: Laparoscopic cholecystectomy
• SH: Smoked 3 packs/day for 30 years; Quit 5 years ago
• PE: Unremarkable

Clinical workup

• Imaging:
  • Chest x-ray showed a left hilar mass with a middle lobe collapse
  • CT scan of the chest/abdomen/pelvis revealed a 4.9 x 5.4 cm left upper lobe mass with bilateral hilar and mediastinal lymphadenopathy
  • CT abdomen/pelvis negative for metastatic disease
  • PET/CT confirmed activity in the lung and lymph nodes
  • MRI of the brain was negative for metastatic disease
• CT-guided biopsy of the left lung mass revealed a differentiated invasive squamous cell carcinoma
• Molecular testing: PD-L1 20%
• Staging: T2bN3M0—IIIB
• ECOG PS 1

Treatment

• Concurrent chemoradiation with weekly carboplatin-paclitaxel
• Imaging 6 weeks after completion showed response in the lung and lymph nodes
• Durvalumab consolidation: 4 cycles with continued tumor control on imaging
• Developed dyspnea and cough after 8 cycles