Considerations for Treating Locally Advanced NSCLC - Episode 5

Effectively Managing Treatment With Durvalumab

Howard (Jack) West, MD:Pneumonitis is a common side effect in this setting, and it was so before durvalumab came to the scene. In the PACIFIC trial, about a quarter of patients had pneumonitis. Although it’s less than 5%, even a small single-digit number of it is grade 3 or higher. It is not uncommon for patients to develop pneumonitis in the weeks or few months after they complete chemotherapy and radiation, and that can be the case just from the chemotherapy and radiation they received. The PACIFIC trial demonstrated a modestly higher, 8% or so, rate of pneumonitis with durvalumab. That was one of the only things, along with the associated symptoms like coughing, that was significantly higher with durvalumab.

We manage this in practice. We managed this before the PACIFIC trial and durvalumab, and we’re definitely managing it in the clinic since then. I’ve had patients for whom I’ve delayed durvalumab for a few weeks to try to tamp down the pneumonitis. I’ve had patients who developed pneumonitis in the first few months on durvalumab; whether it was because of the durvalumab or just going to happen regardless, I can’t say, because it’s very common for patients to develop pneumonitis 2 to 3 or 4 months after they complete chemotherapy and radiation, even if they weren’t on durvalumab.

In that case, I had the patient stop durvalumab and pursue a relatively short course of steroid therapy, and they were able to tamp down on it and were doing better. Their imaging got better, and I resumed durvalumab. He’s been back on that now for a couple of months and is doing very well, without any recurrence of the pneumonitis. So, I would say that this is something we need to get more experience in, clarifying whether patients should not pursue durvalumab if they are already experiencing pneumonitis. But I would say that if patients can have that be a transient issue with or without a short course of steroid management, it can be feasibly pursued. I would just say that if my particular patient had a resumption of a recurrence of their symptoms and imaging findings, I would be far more reluctant to have them go back on and continue on durvalumab.

One of the challenges of durvalumab, though it has introduced better efficacy and broken the impasse of how we’ve treated locally advanced disease for more than a decade, is that it greatly increases the time of treatment. I actually talk with my patients about the general plan for and concept of immunotherapy as we are getting started on chemotherapy and immunotherapy. I plant the seed, and I tell them it’s a probability: more than a possibility but not a definite. I talk about that and the benefit that it confers. I also talk with them about how it’s every 2 weeks for a year beyond the initial 6 or 7 weeks. But my patients, first of all, are very eager to achieve the best outcome that they can, even if that means coming in every 2 weeks for a year beyond an initial 7-week period.

The only thing is that we’re all hearing about the huge promise of immunotherapy, largely in the setting of stage 4 disease. There are TV commercials and news reports, and many of my patients in other settings where it’s not as well studied—or in stage 3 disease, where it now is used—want to know where immunotherapy fits in. When I tell them about it, they often say, “Oh, great, I was going to ask you about that because I saw it on TV” or “I saw it on the news.” They are more relieved and pleased to be getting the cutting-edge therapy that they’ve heard about and absolutely want the benefit of in terms of progression-free and overall survival. That outweighs the challenge of treatment for a year.

The fact is that it’s also not indefinite. It’s a finite period of time. It’s every 2 weeks, and that will potentially be modulated as we get more experience. It may be able to be given as a higher dose less frequently. But right now, it’s every 2 weeks for up to a year. If we run into issues with toxicities or other practical problems, we could always revisit that, but every single one of my patients who I’ve presented the option to has been pleased to have that option and availed themselves of it when available. They have not been so reluctant because of the time issue that they have deferred.

Transcript edited for clarity.


A 60-year-old Asian Woman With Unresectable, Locally Advanced NSCLC

  • A 60-year-old Asian woman presents with complaints of chest pain and shortness of breath. She reports developing a persistent cough about 1 year ago, which she attributed to allergies. In the past month, she has “spit up” blood several times, which caused her to make the appointment.
  • Her history includes:
    • Former smoker, quit smoking at age 35 when she became pregnant
    • Normal BMI, postmenopausal, no history of cardiovascular disease
    • No previous cancer history
  • Evaluation and follow up testing reveal
    • Stage IIIA NSCLC in right bronchi: 3.5-cm tumor with pleural involvement and spread to mediastinal lymph nodes
    • WHO performance status 1
    • Histology: Squamous cell
    • Biomarkers:
      • EGFR,BRAF,ALK/ROS1negative
      • PD-L1 status: 10%
  • After multidisciplinary evaluation, the patient was determined not to be a candidate for surgery, and completed chemoradiotherapy:
    • Carboplatin/paclitaxel doublet plus 55 Gy radiotherapy
    • Achieved stable disease without progression 14 days after completing treatment
    • Began treatment with durvalumab