How I treat NSCLC in the era of checkpoint inhibitors and the COVID-19 pandemic

In this episode, we review how immune checkpoint inhibitors and COVID-19 have changed the management of non-small cell lung cancer (NSCLC).

Jeffrey Crawford, MD, and Susan Blackwell, PA, both of Duke Cancer Institute, join host David H. Henry, MD, to discuss the use of pembrolizumab in NSCLC, two studies of PD-1 inhibitors presented at ESMO 2020, and how COVID-19 has affected NSCLC care, particularly the use of granulocyte colony-stimulating factor (G-CSF).

Diagnosis and treatment of NSCLC

What information should be obtained from a biopsy?

Is this lung cancer? If so, what kind of lung cancer is it: Small-cell lung cancer or NSCLC? Which subtype? Molecular studies for targets, including ALK, KRAS, EGFR, PD-L1.

Treatment with pembrolizumab:

If, for example, a patient has NSCLC and is positive for PD-L1, the treatment of choice is pembrolizumab. A multidisciplinary approach is essential to provide comprehensive education and care to patients taking pembrolizumab (and other immunotherapies). Pembrolizumab can have many side effects, including itching, fatigue, thyroiditis progressing to hypothyroidism, hypophysitis, or another off-target “-itis.” Ms. Blackwell and Dr. Crawford recommend listening to patients, checking the thyroid routinely, and checking cortisol based on index of suspicion.

NSCLC studies presented at ESMO 2020

KEYNOTE-024 5-year OS update: First-line (1L) pembrolizumab (pembro) vs platinum-based chemotherapy (chemo) in patients (pts) with metastatic NSCLC and PD-L1 tumour proportion score (TPS) ≥50%.

The 5-year survival is greater than 30% with pembrolizumab in this study. Historically, 5-year survival has been 1% to 2% in patients treated with chemotherapy alone, Dr. Crawford said. In the control arm of this study, patients received chemotherapy and then crossed over into the pembrolizumab arm, so overall survival was 16% at the 5-year mark. The results suggest immunotherapy should be used first-line if patients meet criteria, Dr. Crawford said. Source: Abstract LBA51. https://bit.ly/3mMYLTK.

EMPOWER-Lung 1: Phase III first-line (1L) cemiplimab monotherapy vs platinum-doublet chemotherapy (chemo) in advanced non-small cell lung cancer (NSCLC) with programmed cell death-ligand 1 (PD-L1) ≥50%. 

Cemiplimab improved overall and progression-free survival in NSCLC patients when compared with chemotherapy alone. Abstract LBA52. https://bit.ly/3mLT6xb.

The effects of COVID-19 on NSCLC care

Logistically, it’s more difficult to see patients during the pandemic, Dr. Crawford noted, but the many potential side effects of immunotherapy make it necessary to see patients regularly in person.

How has COVID-19 affected the concern of febrile neutropenia and the use of G-CSF? Dr. Crawford said the pandemic has heightened the concern about infection risk.

Prior guidelines for G-CSF:

Before the pandemic, guidelines suggested routine prophylactic G-CSF in patients with a greater than 20% risk of febrile neutropenia. In patients with 10% to 20% risk, the recommendation was to consider the use of G-CSF based on the patient population and risk factors.

Pandemic-specific guidelines for G-CSF:

The National Comprehensive Cancer Network (NCCN) recommended relaxing guidelines during the pandemic. If the risk is greater than 20%, NCCN still recommends giving G-CSF. If the risk is 10% to 20%, NCCN recommends giving G-CSF even in the absence of additional risk factors. Dr. Crawford noted that lung cancer patients receiving chemotherapy are typically in the 10% to 20% risk category. Download the COVID-specific NCCN guidelines: https://bit.ly/3jQIco5.

G-CSF biosimilars

The most common complaint with biosimilars is bone pain. Ms. Blackwell advises first treating bone pain with acetaminophen or ibuprofen and warm blankets. For refractory pain, she suggests a low-dose narcotic or dexamethasone. Consider an antihistamine for prophylaxis, as patients report this can help with symptoms.

Show notes written by Ronak Mistry, DO, a resident at Pennsylvania Hospital, Philadelphia.

Disclosures:

Dr. Crawford is on advisory boards at Amgen and Merck, makers of Onpro/Neulasta (pegfilgrastim) and Keytruda (pembrolizumab). Ms. Blackwell and Dr. Henry have no conflicts of interest.

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