Locally Advanced NSCLC: Chemoradiotherapy Versus Surgery

Howard (Jack) West, MD:For locally advanced non—small cell, the real distinction is just where a patient is an appropriate candidate for consideration of surgery that could be and often is preceded by chemotherapy or chemotherapy and radiation concurrently. That is almost always reserved for patients who have stage 3A disease and is very rarely pursued for patients with stage 3B disease, based on our prior experience and the difficulty of achieving good long-term results with surgery for stage 3B. But even in the setting of stage 3A, we need to carefully delineate which patients are good candidates for surgery and which ones are better served by pursuing an approach of chemotherapy and radiation with curative intent.

Patients with multistation nodal disease or bulky disease—and I would say that’s the majority of patients with stage 3A non—small cell lung cancer—are going to be very good candidates for chemotherapy and radiation concurrently, now ideally followed by consolidation durvalumab. A subset may be candidates for surgery, but that’s really something that I would say should be carved out as the minority of patients, not as an expectation for most patients with stage 3A disease.

The question of what is resectable is pretty open-ended and in the eye of the beholder. It depends on the surgeon, and the extent of disease is not really that well defined. Patients may have strong feelings in favor of or against surgery. I think this is the setting where, more than anything else in lung cancer, we really need to rely on a multidisciplinary tumor board setting and multiple disciplines being involved in the decision. I would say that stage 3A non—small cell lung cancer should be generally treated as nonsurgical with the exception of less bulky, under 2 cm or 3 cm, mediastinal nodes with, preferably, just a single nodal station involved. We would like to see that these patients have had a good response to the induction of chemotherapy and radiation before going on to surgery.

What I think is interesting about the PACIFIC trial, and the benefit demonstrated with consolidation durvalumab for a year after chemoradiation, is that we know and have seen a huge benefit in terms of progression-free survival. We also know now that there’s a significant improvement in overall survival, but we have not seen the data yet. This may tip the scale more in favor of chemotherapy and radiation for those marginal cases on the bubble, rather than trying to shoehorn patients in for surgery because they might possibly be candidates. I’m not sure that patients who are on the bubble for surgery are well served by pursuing that if they are not strong candidates, especially when our historical comparisons of chemotherapy and radiation without surgery versus induction chemotherapy or chemoradiation followed by surgery have demonstrated very similar results for the stage 3 population.

Historically, without durvalumab, they’ve been comparable. With durvalumab, I would say this even tips the scale more toward a nonsurgical approach. Yes, I would consider it, but I would really hope to define who’s a good candidate for surgery based on the extent of their disease initially more than using their response to treatment and making a decision on the fly during the course of their treatment. We also don’t want to start the chemotherapy and radiation partway through and then have to pick it up again. Patients who have treatment breaks tend to not do as well.

It’s a minority of patients who will demonstrate progression of disease after chemotherapy and radiation, somewhere in the range of 10%. You can never presume that’s going to be the case, but some will have nodules in the other lung or bone metastases or liver metastases. That’s one of the key things we’re looking for in the weeks immediately after chemotherapy and radiation. We’d also like to see if there’s shrinkage of the cancer. That’s common, but it’s also very common to have ambiguous findings where there is some residual disease where the cancer initially was. Particularly in the weeks immediately after chemotherapy and radiation, we can’t know what is viable and what is not viable. It’s not uncommon for there to be continued shrinkage in the weeks or months that we follow patients for afterward. Just as the chemotherapy and radiation are leading to ongoing effects, we can’t know whether it is just residual posttreatment scarring or dying cancer or still viable cancer. So, it’s very common for there to be ambiguous results but some improvement and not to know whether a patient is likely to be cured or not with further treatment. A minority of patients will demonstrate progression elsewhere.

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