The Use of Durvalumab in Locally Advanced NSCLC

Jyoti Patel, MD:Certainly, this patient has borderline pulmonary function and wasn’t a candidate for surgery, and so we treat him with some caution. Any radiation is going to decrease this pulmonary function test. Generally, I get pulmonary function tests again after radiation’s complete. That’s certainly not compulsory. But this is a patient in whom we’re starting a checkpoint inhibitor, and we would watch him carefully afterward. So, if patients have toxicity from chemotherapy and radiation—so, if they are requiring steroids or requiring oxygen at the completion of chemotherapy and radiation—I would certainly hold back. But this gentleman had small volume disease and tolerated it quite well, so we were eager to start durvalumab. And subset data appear to show that early initiation of durvalumab is also important and may be correlated with a better progression-free survival outcome than later initiation.

In the PACIFIC study, patients received durvalumab every 2 weeks for a year, and until I have more data, I think that’s what I’ll end up doing. Certainly, that’s a lot of therapy for a patient. About 2 months of chemotherapy and radiation followed by a year of every-2-weeks durvalumab—at this juncture, we’ll stop. But again, it’ll be interesting to see what overall survival looks like and whether that is the appropriate thing to do.

Like with any patient who has undergone chemoradiotherapy, toxicities can emerge at any time. And although we see acute radiation pneumonitis, most of our patients who develop radiation pneumonitis do so down the road. And so, we counsel patients regardless of checkpoint inhibitors to call us if they develop any shortness of breath, fevers, or chest discomfort, so we can evaluate them quickly. I think that message is 5-fold intensified in patients with immune checkpoint inhibitors, but certainly, any change in symptoms would necessitate timely evaluation. Patients luckily with this regimen are seen every 2 weeks, as is approved at this juncture, and we would imagine that any cost that’s unexplained, any fever, or any desaturation prompts evaluation.

On top of the pneumonitis, there’s all of the other autoimmunity that we see with checkpoint inhibition. So, we routinely check things like TSH. We would routinely do a thorough review of systems with our patients—has there been any skin changes, any GI changes, any light-headedness? Certainly, I think all of us who are giving these drugs have seen a multitude of symptoms that can happen at any point during therapy.

Transcript edited for clarity.

• A 63-year-old man presented to his PCP with intermittent cough and difficulty breathing on exertion
• PMH: hyperlipidemia well-managed on simvastatin; hypothyroidism, managed on levothyroxine, COPD on inhalers
• Recently quit smoking; has a 40-pack-year history
• PE; intermittent wheezing; ECOG 1
• Creatinine clearance, WNL
• Imaging Studies:
  • Chest X-ray showed opacity in the lung right upper lobe
  • Chest CT revealed a 3.1-cm spiculated mass in the right upper lobe and 2 enlarged right mediastinal lymph nodes measuring 1.5 cm and 1.7 cm; moderate emphysema noted
  • PET confirmed the lung lesion and mediastinal lymphadenopathy without evidence of distant metastasis
  • Brain MRI was negative
• Bronchoscopy with transbronchial lung biopsy and lymph node sampling revealed adenocarcinoma with positive nodes in stations 4R and 7; level 4L was negative
• Genetic testing was negative for known driver mutations
• Staging: T2aN2M0, stage IIIA
• Based on the extent of mediastinal disease and emphysema, the patient’s cancer was deemed inoperable, and he was referred for consideration of concurrent chemotherapy and radiation
• He underwent therapy with cisplatin/etoposide and concurrent thoracic radiotherapy
• Follow-up imaging showed a partial response with shrinkage of the primary and nodal lesions