There’s no question that immune checkpoint inhibitors such as Keytruda (pembrolizumab) and Tecentriq (atezolizumab) are an important addition to the lung cancer armamentarium.

But there are many unanswered questions about how this new wave of therapies should be incorporated into treatment protocols to achieve the best outcomes.

Results of network meta-analysis reported earlier this month in Thoracic Center won’t be the last word on immune checkpoint inhibitors and lung cancer treatment. But it may begin to help researchers and clinicians piece together a complicated puzzle that is getting increasingly so as more treatments become available.

The immune checkpoint inhibitors

PD-1 inhibitors

• Keytruda (pembrolizumab)
• Opdivo (nivolumab)
• Libtayo (cemiplimab-rwlc)

PD-L1 inhibitors

• Tecentriq (atezolizumab)
• Bavencio (avelumab)
• Imfinzi (durvalumab)

CTLA-4 inhibitor

• Yervoy(ipilimumab)

The analysis, which included 15 randomized trials involving almost 9,000 patients, showed that Keytruda plus platinum-based chemotherapy achieved the best results for patients with advanced nonsmall cell lung cancer as measured by a number of commonly used end points: overall survival, progression-free survival and overall response rate.

However, on a subgroup analysis of patients with tumors with high PD-L1 expression, Tecentriq had the highest probability of ranking as the best treatment as measured by overall survival, while the Keytruda plus platinum-based chemotherapy combination was best as measured by progression free survival.

In the group with lowest PD-L1 expression, Opdivo (nivolumab) plus Yervoy (ipilimumab) was the best treatment in terms of overall survival.

Corresponding author Ta-Wei Wu of Taipei Tzu Chu Hospital in Taiwan and colleagues also looked at side effects. Yervoy plus platinum-based chemotherapy, Opdivo plus platinum-based chemotherapy, and Tecentriq had higher rates of serious (grade 3 or higher) treatment-associated adverse events than other treatments.

Network meta-analysis is a type of meta-analysis designed to allow for more comparisons among treatments because it allows for the incorporation of more indirect evidence. Instead of just head-to-head trials, a network meta-analysis factors compares two drugs that have both been compared to a third. For example, if drug A and drug B have both been compared to drug C, a network met-analysis will use factor in the relative effectiveness of A and B by comparing how they stacked up to drug C.

Immune checkpoint inhibitors are drugs that block certain regulatory steps in the immune system. When those steps are unblocked, the immune system “recognizes” cancerous cells and attacks them.