Gray Sheds Light on Considerations When Treating NSCLC With Immunotherapy

Jhanelle E. Gray, MD

Jhanelle E. Gray, MD

Jhanelle E. Gray, MD, recently shared the treatment considerations and decisions she makes when treating patients with non—small cell lung cancer (NSCLC), with a special focus on immunotherapy. Gray, associate member, Director of Thoracic Clinical Research, Moffitt Cancer Center, Tampa, Florida, explained her treatment decisions based on 2 case scenarios during aTargeted Oncologylive case-based peer perspectives dinner.

Case 1

A 63-year-old man presented to his primary care physician with intermittent cough and difficulty breathing on exertion. His past medical history included hyperlipidemia, well-managed on simvastatin; hypothyroidism, managed on levothyroxine. He had a 40-pack-year smoking history. His physical examination showed intermittent wheezing; his ECOG performance status was a 1. His creatinine clearance was within normal limits. Chest X-ray showed opacity in the lung right upper lobe. Chest CT revealed a 3.1-cm speculated mass in the right upper lobe and multiple enlarged mediastinal lymph nodes. PET confirmed the lung lesion and mediastinal lymphadenopathy without evidence of distant metastases. Brain MRI was negative.

Bronoschopy with transbronchial lung biopsy and lymph node sampling revealed adenocarcinoma with positive nodes in stations 4R and 7; level 4L was negative. Genetic testing was negative for known driver mutations. Staging: T2aN2M0, stage IIIa.

TARGETED ONCOLOGY:What are the options for treatment?

Gray:Here at [Moffitt Cancer Center], we generally do not do neoadjuvant chemotherapy. We generally think that these patients have curative disease, and the only way to cure them is to take them to the operating room. If you're doing neoadjuvant, usually you're going to have some sort of surgery. In this case, this patient would not be surgically resectable regardless, so we would do concurrent chemotherapy and radiation therapy.

Based on the extent of mediastinal disease, the patient’s cancer was deemed inoperable, and he was referred for consideration of concurrent chemotherapy and radiation. He underwent therapy with cisplatin/etoposide and concurrent thoracic radiotherapy. Follow-up imaging showed a partial response with shrinkage of the primary and nodal lesions.

TARGETED ONCOLOGY:Does the patient require further treatment?

Gray:Based off the recent PACIFIC data that is currently available, they should at least be offered it. You need to have that discussion with the patient.

The PACIFIC trial is a randomized phase III study of randomized 2:1 durvalumab [Imfinzi] versus placebo for these patients. The primary endpoint that was ready for the time of presentation was progression-free survival [PFS]. The data is not yet ready for overall survival [OS]. The patients were enrolled on the study following completion of concurrent chemoradiation, so they had to at least achieve stable disease. Patients that progressed off the bat weren't eligible for the study. People had a good PFS, and it was regardless of PD-L1 status, which I think fits with this population of patients where it's going to be challenging to get tissue collected on these patients following completion of concurrent chemoradiation therapy.

I think some people are waiting for the mature OS data. I think we all are waiting, but I think people are willing to act on it. There wasn't a big increase of pneumonitis over what you would expect, and I think that is definitely something that is reassuring. You're not exposing these patients to undo toxicity.

The timing of the treatment with durvalumab in reference to when the radiation was completed is another thing to note. The timing matters, and the closer you can give it to the radiation therapy, in part due to the whole hypothesis and the data out there that radiation therapy is immune-potentiating, it's going to be very important moving this drug forward.

Case 2

An 81-year-old man presented with symptoms of coughing, dyspnea, upper back pain, and fatigue requiring frequent rest. His past medical history included hypercholesterolemia, controlled on pravastatin; hypertension, controlled on verapamil; psoriatric arthritis, under control. He was a former smoker; he is physically active and plays golf weekly. A chest CT revealed a 1-cm solid mass in the left upper lobe and lymphadenopathy in the left hilar and bilateral mediastinal nodes. PET/CT imaging showed F-FDG uptake in the lung mass, left hilar, and both mediastinal lymph nodes, and thoracic spine (T5/T6).

Bronchoscopy and transbronchial lung biopsy were performed. Pathology showed squamous cell carcinoma PD-L1 expression by immunohistochemistry 223C assay, tumor proportional score (TPS) was 65%. His diagnosis was stage IV squamous NSCLC.

TARGETED ONCOLOGY:What is the prognosis for this patient?

Gray:If they respond to immunotherapy, this patient's prognosis could be 2 to 3 years, especially with their high PD-L1 expression level, but we have also seen where patients with high PD-L1 expression levels don't respond to immunotherapy, such as pembrolizumab [Keytruda]; however, the potential is definitely there.

TARGETED ONCOLOGY:Are you routinely testing for PD-L1 expression in newly diagnosed patients?

Gray:Yes, we would test PD-L1 expression on all newly diagnosed stage IV patients that have NSCLC, including squamous and nonsquamous [histologies]. We're using the 22C3 DAKO FDA-approved antibody test. We have that in-house. Turnaround time is about 2 to 3 days on that once they have slides.

TARGETED ONCOLOGY:What are the treatment options for the patient?

Gray:In the setting of well-controlled psoriatic arthritis and a high TPS score, I think it's reasonable to try the patient on immunotherapy. I think you just have to discuss the risk and benefits with the patient. If they have any complications from it, from an immune-related adverse event standpoint, [there’s a] low threshold to switch them over to chemotherapy.

TARGETED ONCOLOGY:Is there a potential role for radiation therapy to address his symptoms of dyspnea or back pain?

Gray:It depends on if the pain can be controlled with pain medications or not, but for right now, I don't think it needs to be.

TARGETED ONCOLOGY:What are the options for systemic therapy?

Gray:For this patient, chemotherapy and immunotherapy are the options, especially for someone with squamous cell.

The patient was started on pembrolizumab.

TARGETED ONCOLOGY:How does his older age and good performance status factor into this choice?

Gray:At his age and performance status, he should be able to tolerate pembrolizumab. I think it's more driven by the PD-L1 status.

TARGETED ONCOLOGY:Do precautions need to be taken considering his well-managed psoriatic arthritis?

Gray:I think you do have to take precautions for the psoriatic arthritis, get the rheumatologist involved upfront and let them know what you're doing. If it starts to require treatment, then you may need to pivot on therapy also.