Recommendations for Treating Locally Advanced NSCLC

Hossein Borghaei, DO, MS:I think, first of all, it’s very important to have multidisciplinary team discussions about these patients. I think an open discussion with the radiation oncologist and medical oncologist is absolutely essential. Coordination of care. I think having office staff members such as nurses, fellows, residents who are well versed in identifying immune-related adverse events, particularly pneumonitis, in this patient population is important. So a lot of education has to go into building a team that is capable of taking care of these patients.

I think if there are any questions, reaching out to colleagues who might have more experience dealing with this locally advanced disease is also important. I think a lot of us are available to have a discussion as to whether a patient is appropriate for treatment with, again, what I would consider to be a fairly aggressive regimen. I think not shying away from offering this treatment to a patient who’s a little bit older is also another important point. Again, if we go based on performance status of a patient more than how old they are, I think we can make better decisions in that category. And I think that the data speak for itself, but I think a lot of the patients who walk into our clinics with locally advanced disease could potentially benefit from concurrent chemotherapy radiation followed by durvalumab.

The other area that we can discuss that has not been adequately answered is those patients who cannot get concurrent chemotherapy radiation but get sequential chemotherapy followed by radiation, and whether those patients should be exposed to durvalumab. That was not tested in PACIFIC. So we don’t have specific guidelines or recommendations for that. I think practitioners are going to develop their own interpretation of PACIFIC, meaning that some feel comfortable offering durvalumab to patients who get sequential chemotherapy and radiation. And I think I put myself in that category. And there are patients for whom they are going to stick strictly to the data and say, “If it’s not concurrent, I’m not going to offer durvalumab.” And I think that, again, depends on the individual’s interpretation of the data, and it’s absolutely appropriate.

Again, that’s basically what I have to say for community oncologists dealing with patients with locally advanced disease. We’re available for discussion and consultations if needed. I also recommend management through a multidisciplinary team and being aware of the potential toxicities.

We need to cure these patients. We need to have a cure rate. So I’m very curious to see what the long-term follow-up of patients who are treated per PACIFIC is going to show us. I want to see 5-year, 10-year survival rates, and I think the unmet need here is that we still need to come up with treatments that are better tolerated and less toxic and treatments that, in fact, can increase our overall survival even above and beyond where we are with the PACIFIC study. Again, it’s a first step. It’s a good first step in this disease. It’s a major improvement after many decades of not having significant improvement, but I don’t think the work is done. The story with PD-L1—negative tumors, as we just discussed, definitely deserves attention, and we should address it. And also, not to give up and not to sit back. Be comfortable but press ahead and try to come up with even better treatment options for our patients, both in terms of toxicity and also survival.

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