Challenges in Managing Locally Advanced NSCLC

Hossein Borghaei, DO, MS:What we have here is a case of a 72-year-old female, with a 30-pack-per-year smoking history, who presented initially for a work-up because of weight loss and dyspnea. A chest x-ray had shown a left-upper-lobe mass. This was followed by a CAT [CT; computed tomography] scan and a PET [positron emission tomography] scan that actually showed bilateral hilar and mediastinal adenopathy in addition to a left-upper-lobe mass and possible collapse of the left upper lobe. Eventually, a biopsy confirmed that this was a squamous cell carcinoma, and she was staged as stage IIIb because of the bilateral hilar mediastinal adenopathy. She presents now for recommendations for treatment. Appropriately, the patient was offered concurrent chemotherapy and radiation with weekly carboplatin and paclitaxel for the treatment of this stage IIIb non—small cell lung cancer. Appropriately, this was followed by treatment with durvalumab, which is based on the PACIFIC study that we’re going to discuss later in this program. We’re here to discuss the data surrounding the use of durvalumab and some of the other issues for the management of patients with stage IIIb non–small cell lung cancer.

Unfortunately, the prognosis of patients who are diagnosed with stage IIIb non—small cell lung cancer is not good. We’re hoping that things are improving based on the available data that, again, we’re going to discuss. But on average, depending on the studies that you look at, the 5-year survival of patients with this stage of disease ranges anywhere from 15% to 20%. There had not been a lot of significant changes in the management of this disease, again, until the PACIFIC study. But overall, we feel that this locally advanced stage of non–small cell lung cancer is an area for which we have been waiting for major improvements and outcomes just because, again, we’ve not been able to make significant progress in improving the prognosis of these patients.

The role of molecular testing in the management of patients with locally advanced disease is still under investigation. Certainly, for patients with a diagnosis of adenocarcinoma, I think I would personally have ordered additional molecular testing to see if there are driver mutations. This is not to say that I would go to targeted therapies immediately. I think if a patient is an appropriate candidate for it, concurrent chemotherapy and radiation followed by durvalumab is the standard of care. However, because of the fact that these patients are at a higher risk of disease recurrence, I think it would be important to have the molecular data available, such that if there is a driver mutation at the time of progression, one can easily and quickly initiate systemic therapy for the patient. There are clearly studies that are ongoing trying to look at the role of targeted therapies. That’s a little bit outside the scope of this discussion.

For patients with squamous cell carcinoma of the lung, the story is a little bit different. We haven’t really been able to identify clear driver mutations that are targetable. There is a very large, national study, the Lung Master Protocol. It used to be SWOG S1400, and now it’s changing. It is exploring the possibility of identifying particular molecular drivers for patients with squamous cell carcinoma. So at this stage, we don’t have that. It is clear from some of the data that we have that patients who have either light smoking history or a never-smoking history who get squamous cell carcinoma should be tested because driver mutations can be found. In this case, I would say I wouldn’t necessarily think that we have to test this particular patient, but I don’t see any reason why, if someone wanted to look for specific genetic alterations, we couldn’t do it. So it’s an area that still requires further refinement.

Transcript edited for clarity.

Case: A 72-Year-Old Female With Stage IIIB NSCLC

Initial presentation

• A 72-year-old woman presented with a 17-lb weight loss and dyspnea
• PMH: HTN and hyperlipidemia
• PSH: Laparoscopic cholecystectomy
• SH: Smoked 3 packs/day for 30 years; Quit 5 years ago
• PE: Unremarkable

Clinical workup

• Imaging:
  • Chest x-ray showed a left hilar mass with a middle lobe collapse
  • CT scan of the chest/abdomen/pelvis revealed a 4.9 x 5.4 cm left upper lobe mass with bilateral hilar and mediastinal lymphadenopathy
  • CT abdomen/pelvis negative for metastatic disease
  • PET/CT confirmed activity in the lung and lymph nodes
  • MRI of the brain was negative for metastatic disease
• CT-guided biopsy of the left lung mass revealed a differentiated invasive squamous cell carcinoma
• Molecular testing: PD-L1 20%
• Staging: T2bN3M0—IIIB
• ECOG PS 1

Treatment

• Concurrent chemoradiation with weekly carboplatin-paclitaxel
• Imaging 6 weeks after completion showed response in the lung and lymph nodes
• Durvalumab consolidation: 4 cycles with continued tumor control on imaging
• Developed dyspnea and cough after 8 cycles