Treatment Considerations in Non-Small Cell Lung Cancer

Stephen Liu, MD:The treatment options for a patient with a stage III non—small cell lung cancer are quite varied and depend on the specific clinical circumstance and reflect the heterogeneity of stage III non–small cell lung cancer overall. Our standard treatment for a stage III non–small cell lung cancer is still definitive concurrent chemoradiation. The chemotherapy used is either cisplatin and etoposide or weekly carboplatin and paclitaxel. Some use of cisplatin and pemetrexed in this setting is also acceptable and in our current guidelines. However, there are different strategies.

For a patient with a potentially resectable stage III non—small cell lung cancer, surgery can be incorporated, and trimodality therapy would be appropriate. Surgery would not be the first modality. We would typically start with neoadjuvant chemotherapy, then surgery, then postoperative radiation therapy or neoadjuvant chemoradiation followed by surgery, followed by consolidation immunotherapy in more modern eras. The incorporation of surgery, though, depends on the size of the tumor, the location, the feasibility, the experience of the surgeon, the underlying lung function, and the location of specific lymph nodes. For example, if bulky N3 lymph nodes are involved, surgery is typically not something that would pop up on our radar. However, for someone with a T3N1 or T4N1 that could potentially be resectable, most academic centers, most experienced multidisciplinary teams would try to incorporate surgery if possible.

When we decide on our treatment approach for someone with stage III non—small cell lung cancer, it’s important the case be discussed in a multidisciplinary team. The first branch point is really, is the patient a candidate for surgery and is this a potentially resectable tumor? If it is, we need to work closely with a radiation oncologist, with our thoracic surgeon to construct a neoadjuvant plan and a surgical sequence to optimize the outcomes for that patient.

If it’s an unresectable non—small cell lung cancer, then our standard treatment is chemoradiation. While we prefer concurrent chemoradiation, we do have to understand that there can be some impact on underlying lung function. It’s important to look at the pulmonary function tests, the pulmonary reserve, and be sure this patient would be able to tolerate the definitive radiation therapy. While the concurrent administration of chemotherapy improves efficacy and improves outcomes for patients with stage III non–small cell lung cancer, it does increase toxicity. A sequential approach would be less toxic, though potentially less effective. So, it is a balance. While we certainly want the best cancer outcomes, it’s important we leave patients with adequate respiratory function to have a good quality of life. Working with our pulmonologist and our radiation oncologist is important to determine if this patient is a candidate for concurrent chemotherapy. Or would that be too toxic in the context of their underlying lung function, and should we then pursue a sequential approach?

We also need to consider the patient’s performance status. Are they a good candidate for chemotherapy? We have different chemotherapy options. Cisplatin and etoposide at full doses would not be an option for all patients. It requires good underlying kidney function. We have to be sure that patients have adequate performance status to receive what can be a fairly intense chemotherapy regimen. The weekly carboplatin and paclitaxel is a bit gentler. It can be myelosuppressive. We can still see neuropathy but not quite as nephrotoxic.

The regimens are different in terms of their timing, and the distance to chemotherapy centers, to radiation centers, may also influence the access to care and the type of regimen you choose. There are a lot of important anatomic considerations, physiological considerations. Laboratory and underlying lung function need to be considered, but so do social circumstances and how far those patients need to travel and their support networks at home to get them through what can be a fairly intense and fairly toxic treatments.

Transcript edited for clarity.

Case: A 62-Year-Old Male With Stage III NSCLC

Initial presentation

• A 62-year-old man presented with a 2-month history of cough, wheezing, and loss of appetite
• PMH: Hypertension, medically treated
• SH: 30 pack-year smoking history; daughter to be married in 11 months, and wants to attend the wedding
• PE: Right lower lobe wheezing on auscultation

Clinical workup

• Labs: WNL
• PFT: FEV₁/FVC 60%; DLCO 55%
• Chest/abdomen/pelvic CT showed a 6.1-cm solid pulmonary lesion in the right lower lobe, right hilar and intrapulmonary lymph node involvement; no evidence of distant metastases
• PET scan showed large focal hypermetabolic activity in the right lower lobe and small hypermetabolic activity in the surrounding area
• Contrast‐enhanced MRI of the head showed no brain metastases
• Bronchoscopic biopsy of the RLL mass and hilar node revealed squamous NSCLC
• Staging: T3N1M0 — IIIA; ECOG PS 1
  • Unresectable NSCLC based on the extent and location of disease

Treatment

• Patient was started on cisplatin 50 mg/m²on days 1,8,29 and 36; etoposide 50 mg/m²days 1-5 and 29-33; concurrent RT
• No disease progression after chemoradiation
• Durvalumab 10mg/kg IV q2W was started and dose was tolerated well
• Initial follow-up at 2 months showed partial response, with shrinkage of primary and nodal lesions