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Overcoming the challenges of immunotherapy in non–small cell lung cancer

Presented by
Dr Sarah B. Goldberg, Dr Melissa Lynne Johnson, Dr Alexander Chi
ASCO 2019
Medical writer: Jasenka Piljac Žegarac, PhD

Several experts discussed the current challenges in the use of immunotherapy in non–small cell lung cancer (NSCLC)—the most common type of lung cancer—as well as strategies to overcome them, in the Interactive Case-Based Session “Challenges in Use of Immunotherapy in NSCLC: Where the Rubber Meets the Road,” held May 31. The session was chaired by Jyoti D. Patel, MD, FASCO, of the University of Chicago Medical Centre.

“The objectives are to understand the factors that affect the risk/benefit ratio of treatment with immune checkpoint inhibitors (ICIs) in patients with advanced NSCLC and to understand what challenges this poses in patients with dysregulated immunity, chiefly those with autoimmune diseases,” Dr. Patel said.

She further noted that it is important to understand: (1) how the data hold up in patients encountered in the clinic and not just those enrolled in clinical trials; (2) which patients are too high risk for ICIs; (3) what the boundaries are, if any, beyond which it is no longer safe to treat patients with ICIs; and (4) which clinicians need to be part of the care team for high-risk patients.
Immunotherapy in patients with underlying autoimmune disease

Sarah B. Goldberg, MD, of the Yale University School of Medicine, presented the first case: a 55-year-old man with a history of ulcerative colitis (UC) and smoking who was diagnosed with stage IV NSCLC. He had an ECOG performance status of 1. She asked the attendees how likely they were to treat this patient with immunotherapy as part of first-line therapy. The informal survey showed that the majority of respondents (approximately 56%) selected pembrolizumab alone as their therapy of choice, followed by carboplatin/pemetrexed/pembrolizumab (approximately 28%).

Dr. Goldberg said that it was “very reasonable to consider pembrolizumab as part of first-line treatment” in this patient because his UC was fairly mild and had been well controlled on sulfasalazine, but noted that there “should be a discussion with the patient about the risks and benefits of immunotherapy and the possibility of worsening UC.”

She summarized the data from the KEYNOTE-024 and KEYNOTE-189 trials, which demonstrated that pembrolizumab alone and pembrolizumab in combination with chemotherapy improved survival in patients with a PD-L1 tumour proportion score greater than or equal to 50% and any PD-L1 status, respectively.2,3

She continued by presenting the data on the prevalence of ADs in patients with lung cancer and noted that ADs are fairly common in this patient population. A total of 13.5% of patients in one study reported having any AD.4

“If you treat patients with lung cancer, then you will see patients with ADs,” she said. “The most common is rheumatoid arthritis at about 6%.”

Psoriasis (2.8%) was the second most common autoimmune comorbidity, followed by polymyalgia rheumatica (1.8%), Addison disease (1.0%), and systemic lupus erythematosus (0.9%).4
Immunotherapy in patients with renal insufficiency

Melissa Lynne Johnson, MD, of the Sarah Cannon Research Institute, presented the second case: a 59-year-old female with a history of smoking, non–insulin-dependent diabetes mellitus, gastroesophageal reflux disease (GERD), and hypertension who was diagnosed with metastatic adenocarcinoma with confirmed liver lesions. She was treated with four cycles of carboplatin/pemetrexed/pembrolizumab, during which time her creatinine increased from 0.85 to 1.33. On the third cycle of maintenance pemetrexed/pembrolizumab, the patient’s creatinine had increased to 2.5.

Dr. Johnson noted that this patient had additional risk factors for developing acute kidney injury (AKI) beyond use of immunotherapy, which included a history of diabetes and hypertension that were moderately well controlled, as well as a history of GERD for which she was treated with proton pump inhibitors (PPIs).

She outlined several important aspects that clinicians need to consider in patients on chemotherapy/immunotherapy combinations with worsening AKI, including ruling out alternative causes of AKI, grading the severity of kidney injury, and seeking an early nephrology consultation.
Immunotherapy for patients with poor performance status stage III disease

The third case was presented by Alexander Chi, MD, of West Virginia University. He discussed the treatment approach in an 84-year-old female with underlying chronic obstructive pulmonary disease and poor pulmonary function tests who was diagnosed with stage IIIb NSCLC. The patient’s MRI was negative for metastatic disease.

Dr. Chi said that, aside from the PACIFIC trial, “there is not a lot of data guiding the utilization of immunotherapy, mainly ICIs, in the stage III setting.”

In reflecting on the prevalence of pulmonary toxicity in NSCLC trials to date, he noted that the incidence of severe radiation pneumonitis was fairly low with concurrent chemotherapy with intensity-modulated radiation therapy (RTOG 0617 trial)7—only 3.5%—and that it was less than 5% with chemoradiation plus durvalumab combination therapy (PACIFIC trial).8 However, he also emphasized that the patients included in these trials are not necessarily representative of the patients encountered in the clinics because, in addition to having an excellent functional performance status, most of them had no prior autoimmune disease, no immunodeficiency of immunosuppression, and no primary cancer within 3 to 5 years.

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