Small-cell lung cancer (SCLC) accounts for about 10% to 15% of all lung cancers. Most of the time, when SCLC is diagnosed, it is at an advanced stage known as an extensive stage. At this point, the prognosis is very poor and treatment options are limited. The approval of an immunotherapy agent, pembrolizumab, would provide another option that would revolutionize SCLC treatment.

Pembrolizumab was granted accelerated approval based on the phase II KEYNOTE-158 basket study (NCT02628067). This study had 10 tumor types, including microsatellite instability high, which included advanced SCLC. In KEYNOTE-158, patients were treated with pembrolizumab 200 mg IV every 3 weeks for 2 years or until disease progression, unacceptable toxicity, or study withdrawal. The primary endpoint was objective response rate (ORR). Patients had to have progressed after first-line therapy with unresectable disease with a performance status of 0 or 1. The median age was 63 years, and 75% of patients were male.

Of all the tumors, 39% were PD-L1 positive and 47% were PD-L1 negative. At 9.3-month follow-up, the ORR was 18.7%. Median progression-free survival was 2 months, and median overall survival was 8.7 months. The PD-L1-positive group had higher response rates, including overall survival. Adverse effects occurred in 60% of the patients and consisted of fatigue (14%), pruritus (12%), hypothyroidism (12%), decreased appetite (10%), and nausea (10%). Of these patients, 12% had grade 3 or 4 side effects. In addition, there were two fatal treatment-related adverse effects, pneumonia and encephalopathy, which were discovered in the safety follow-up.

In the KEYNOTE-028 basket trial, the SCLC arm consisted of 163 patients from March 2014 to May 2015, of whom 145 were PD-L1 positive, with a median age of 60.5 years. Ultimately, 24 patients were treated because others did not meet inclusion criteria or had reasons not stated. All patients had received previous chemotherapy or immunotherapy, and some had received two lines of chemotherapy.

In this trial, patients received pembrolizumab 10 mg/kg every 2 weeks for 24 months or until progression, intolerable toxicity, or withdrawal. The ORR was 33% in patients with extensive-stage SCLC. Median progression-free survival was 23.8%, and overall survival was 9.7 months. All patients experienced side effects of fatigue, cough, arthralgia, diarrhea, insomnia, and rash. Median time to response was 2 months, and median duration of response was 19.4 months. Secondary endpoints of progression-free survival were 23.8%. Both of these studies show that pembrolizumab achieved higher response rates and confirmed the use of pembrolizumab in SCSL to increase and improve survival rates.

Pembrolizumab is a promising treatment for SCLC and further research is needed. It is currently also being considered in combination with etoposide- and platinum-based chemotherapy in the phase III KEYNOTE 604 study. Pembrolizumab shows promising results for changing the face of treatment for SCLC pending results of the phase III trial.

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