Considerations for Treating Locally Advanced NSCLC - Episode 1

Reviewing a Case of Locally Advanced NSCLC

Howard (Jack) West, MD:The patient is a 60-year-old Asian woman with a prior smoking history but really no significant past medical history and no cardiovascular issues. She’s postmenopausal and has a good performance status of 1. She, as I said, has a smoking history; a history of a cough that goes back about a year; and some right chest pain, but that was pretty stable. She developed hemoptysis. That’s what led her to seek medical attention and, at that time, she was found on imaging to have a right chest lesion. She had a bronchoscopy that showed her 3.5-cm right medial chest mass was a squamous non—small cell lung cancer. Her imaging also demonstrated that she had some nodal involvement, particularly that mediastinal nodes were enlarged. It also appeared that she likely had pleural involvement. She had her case presented at a multidisciplinary tumor board, and it was determined that surgery was not the appropriate way to go but that she was a potential candidate for curative therapy with chemotherapy and radiation.

I should also mention that she had additional pathology testing for various molecular markers, with no driver mutation seen, and she had PD-L1 testing done that returned as 10%, although that’s not of critical importance in this setting outside of advanced disease. In any event, she then started on concurrent chemotherapy and radiation. She received a definitive dose of chest radiation daily, and she went on a common chemotherapy regimen of weekly carboplatin and paclitaxel. She tolerated that well without any prohibitive toxicity issues over the course of her several weeks of treatment. She was able to more or less maintain her weight and eat. And then she had some imaging done a couple of weeks after her completion of chemotherapy and radiation that looked favorable, with no evidence of any disease progression and some ambiguous findings, which we often see after chemotherapy and radiation, in terms of how much shrinkage. You don’t know what’s residual tumor tissue or dead or dying. Then she was able to start on consolidation durvalumab.

I would say this is a pretty typical case setting. We have a lot of patients who get chemotherapy and radiation for stage 3 lung cancer, which is about a third of our patients in terms of how they present. As long as they have a good enough performance status, concurrent chemotherapy and radiation is known to be associated with a significant improvement in overall survival compared with a sequential approach. But the big challenge has been that for the last 10 to 20 years, since we’ve gotten information showing that there is a survival benefit for concurrent over sequential therapy, we haven’t had any advances until very recently. We’ve tried pursuing consolidation chemotherapy after the chemotherapy and radiation are completed. That has not demonstrated any significant survival benefit in several trials. We’ve tried targeted therapies like gefitinib and other agents. We’ve tried adding bevacizumab, and these attempts have not only not led to benefits but also have been detrimental. We’ve tried escalating the radiation dose and found that that, too, was not associated with a benefit but led to harm compared with our old standards.

And so, it’s been difficult to break the bottleneck and get beyond this impasse of chemotherapy and radiation for 6 or 7 weeks. It wasn’t until the demonstration of significant benefits with durvalumab as consolidation therapy that we finally demonstrated a benefit that was clinically significant and moves beyond where we’ve been stuck for more than a decade for stage 3 lung cancer.

In the setting of locally advanced stage 3 non—small cell lung cancer, we don’t focus as much on histology as we would in advanced disease, because the most common chemotherapy regimens that are used, not just in the United States but globally, are not histology specific. The most common and best-studied regimens have been either cisplatin and etoposide with concurrent radiation or carboplatin and paclitaxel with radiation. A third would be cisplatin and vinorelbine, at least globally if not so much in the United States. But all of these are fine choices with pretty comparable results in patients, whether they have a squamous or nonsquamous histology. Though when we look at that, we have not differentially treated patients unless we’re considering a regimen such as platinum and pemetrexed, which is an option not as well studied as these others but an acceptable alternative—but only for the patients with nonsquamous histology. Otherwise, since we’re usually using weekly carboplatin and paclitaxel or cisplatin and etoposide, these are both acceptable and histology agnostic.

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