Hossein Borghaei, DO, reviews the currently accepted first-line treatment recommendation for extensive-stage small cell lung cancer: a triple combination of carboplatin, etoposide, and a checkpoint inhibitor (atezolizumab or durvalumab). He provides an overview of the IMpower and CASPIAN trials.
Hossein Borghaei, DO: How do we go about managing this patient in 2021? There are at least 2 phase 3 studies that have shown efficacy of a combination of chemotherapy and immunotherapy in this patient population. As many of you are aware, for a long time, for close to 2½, 3 decades, the standard treatment for patients with metastatic small cell [lung cancer] was a combination of a platinum agent plus etoposide in the first-line setting. Unfortunately, the overall survival and prognosis of patients with this diagnosis with this treatment was rather poor.
With the introduction of the checkpoint inhibitors into clinical practice in many malignancies, including non–small cell lung cancer, there was an intense interest to investigate the role of the available checkpoint inhibitors in management of patients with small cell lung cancer. Most of the studies were initially done in patients who had had chemotherapy and had evidence of disease progression. They had immunotherapy-based studies in the maintenance setting, which unfortunately didn’t show significant clinical activity until IMpower 132 was presented.
In IMpower 132, patients with similar characteristics as our patient discussed here, with metastatic small cell lung cancer, were randomized to carboplatin-etoposide with or without atezolizumab. Then patients who were having evidence of a response after about 4 cycles of the 3-drug combination were offered atezolizumab in a maintenance setting and patients were followed. The study confirmed that both PFS [progression-free survival] and overall survival was superior in the patient population that received the atezolizumab. Improvement in survival was about 2½ to 3 months. That’s not a spectacular improvement; however, it’s enough to indicate that the standard of care now should be a combination of chemotherapy plus a checkpoint inhibitor, in this case atezolizumab.
CASPIAN is another study, also conducted in patients with metastatic small cell. It had a very similar design except that in CASPIAN there were 3 arms, including an arm where patients were treated with a combination of a durvalumab and tremelimumab. Tremelimumab is an anti-CTLA4 antibody, but the initial presentation of CASPIAN concentrated on analysis of patients who had received standard chemotherapy vs same chemotherapy with durvalumab. This phase 3 randomized study also confirmed that the patients who received chemotherapy with a checkpoint inhibitor had an improvement in overall survival, in the order of 2, 2½ months, indicating and confirming that the standard of care for this patient population is a combination of chemotherapy and immunotherapy followed by immunotherapy.
Toxicities of this triple combination in both studies were actually quite manageable, meaning that there was not a significant increase reported in the immune-related adverse events in this patient population. Obviously, with the combination of the 3-drug regimen, you expect a little more toxicities. But the ones we worry about in terms of pneumonitis, renal dysfunction, or immune-related adverse events did not appear to be significantly worse. Keep in mind that in CASPIAN, treatment in a maintenance setting with the checkpoint inhibitor continued until disease progression and the case was similar in IMpower133—basically patients who were responding but continue to receive the checkpoint inhibitor.
Now we have a new standard of care. Most of our patients are offered treatment with a 3-drug combination that includes the old-fashioned, usually in the United States anyway, carboplatin plus etoposide with a checkpoint inhibitor, in this case atezolizumab or durvalumab, and then patients are followed.
Transcript edited for clarity.