Can Immunotherapy Improve Survival in NSCLC?

Patients with advanced non–small-cell lung cancer (NSCLC) who received immunotherapy, in particular immune checkpoint inhibitors in the first-line setting, lived longer than those who received chemotherapy, according to the findings of a meta-analysis and individual patient-level study recently published in JAMA Network Open.

“The findings of [the study] are well established over the last 3 to 5 years from multiple studies,” James Herman, MD, a medical oncologist at UPMC Hillman Cancer Center told Cancer Network. “It’s something we already knew.”

Take, for example, the 5-year follow-up results of the KEYNOTE-001 trial that confirmed the efficacy of pembrolizumab in NSCLC long-term. The results were presented at the 2019 American Society of Clinical Oncology (ASCO) Annual Meeting and showed that the patients with advanced NSCLC who received pembrolizumab had improved survival compared with what has been historically seen with chemotherapy.

The study authors explained that despite the progress that has been made with immunotherapy in NSCLC, the results have been “inconsistent” in randomized clinical trials. For example, while KEYNOTE-024 and CheckMate-057 showed a survival benefit for immune checkpoint blockade compared to chemotherapy, the CheckMate-026 trial, which evaluated nivolumab in the first-line setting, did not.

“Additionally, important questions remain regarding which immunotherapeutic strategy can be deployed to the best benefit,” the study authors reasoned.

The researchers systematically identified randomized clinical trials published up until June 2018 that evaluated immune checkpoint inhibitors, tumors vaccines, or cellular immunotherapy in patients with advanced or metastatic NSCLC. Overall, 31 trials and 14,395 individual patients were identified and included in the meta-analysis, and for the individual patient-level study, 1,833 patients were included.

The analysis revealed that patients who received immunotherapy overall had significantly better overall survival (OS; HR=0.76; 95% CI, 0.71–0.82; P < .001) and progression-free survival (PFS; HR=0.76; 95% CI, 0.71–0.82; P < .001). Specifically, immune checkpoint inhibitors were also associated with significantly better OS (HR=0.75; 95% CI, 0.68–0.82; P < .001) and PFS (HR=0.76; 95% CI, 0.68–0.84; P < .001)

Improved PFS for immune checkpoint inhibitors was also seen across various immune checkpoint inhibitor combinations in the first-line setting compared with chemotherapy: dual immune checkpoint inhibitors (HR=0.83; 95% CI, 0.72–0.96; P = .01), immune checkpoint inhibitors in combination with chemotherapy (HR=0.68; 95% CI, 0.58–0.80; P < .001), immune checkpoint inhibitors in combination with anti–vascular endothelial growth factor receptor therapy and chemotherapy (HR=0.61; 95% CI, 0.52–0.72; P < .001), and maintenance immune checkpoint inhibitors (HR=0.52; 95% CI, 0.42–0.65; P < .001). In addition, superior PFS was seen for pretreated patients who received immune checkpoint inhibitors compared with chemotherapy (HR=0.85; 95% CI, 0.77–0.94; P = .002).

The analysis also showed that pembrolizumab in combination with platinum-based chemotherapy in the first-line setting had superior survival outcomes compared to other immune checkpoint inhibitors: nivolumab, atezolizumab with platinum-based chemotherapy, and ipilimumab. The study authors asserted that based on this, “[Pembrolizumab with platinum-based chemotherapy] should be the preferred choice for patients with advanced NSCLC.

Herman, however, cautioned against this.

“I don't know that [pembrolizumab] is necessarily better, but it is further along,” he said. He explained that pembrolizumab is “more established,” has more studies, and was the first to receive FDA approval compared with other immune checkpoint inhibitors.

“The evidence is stronger for [pembrolizumab],” he said. “But the atezolizumab studies are more recently published and show a survival benefit as well.”