medwireNews: Combining a PD-L1 inhibitor with an etoposide–platinum chemotherapy regimen may be the optimal first-line treatment for patients with extensive-stage small-cell lung cancer (SCLC), network meta-analysis findings suggest.
This combination was associated with better overall survival (OS) and disease control than other regimens, such as those containing bevacizumab, without excess toxicity, report Yan Huang (Sun Yat-sen University Cancer Center, Guangzhou, China) and co-authors in JAMA Network Open.
The researchers analyzed data for 4838 participants of three phase 2 and 11 phase 3 randomized controlled clinical trials.
They found that individuals treated with a PD-L1 inhibitor (durvalumab or atezolizumab) plus etoposide and platinum-based chemotherapy had significantly better OS than those who received etoposide–platinum chemotherapy alone, with a hazard ratio for survival of 1.40.
Individuals who received irinotecan plus platinum-based chemotherapy also had significantly better OS that those who received etoposide plus platinum-based chemotherapy (HR=1.29), but there were no significant differences among the patients who received etoposide–platinum chemotherapy plus ipilimumab or bevacizumab, and etoposide–platinum chemotherapy alone.
Progression-free survival (PFS) was greatest with bevacizumab plus etoposide and platinum-based chemotherapy, at a significant HR of 1.54 relative to etoposide–platinum chemotherapy alone, while the HR for irinotecan–platinum chemotherapy was a significant 1.30 versus etoposide and platinum-based chemotherapy. There were no significant PFS differences among the other regimens tested.
The only regimen associated with a significantly improved disease control rate (DCR) was a PD-L1 inhibitor plus etoposide–platinum chemotherapy, with individuals who received this treatment a significant 58% less likely to have uncontrolled disease than those receiving etoposide plus platinum chemotherapy alone.
Safety analyses revealed that the bevacizumab plus etoposide–platinum regimen was associated with a significant 4.24-fold increase in the risk for grade 3 to 5 treatment-related adverse events (TRAEs) compared with the irinotecan–platinum regimen, while the risk was a significant 2.71-fold higher with etoposide–platinum chemotherapy.
By contrast, “[t]he addition of PD-L1 inhibitors to etoposide-platinum chemotherapy caused no more toxic effects in general,” the researchers remark.
Finally, the team performed ranking analyses to determine which regimens were most likely to rank highest for each of the outcomes.
They found that the PD-L1 inhibitor plus etoposide–platinum regimen had the highest probability of being ranked first for OS (87%) and DCR (97%), while the bevacizumab plus etoposide–platinum chemotherapy regimen had the highest likelihood of ranking first for PFS (87%) and TRAEs (89%).
Huang et al conclude that their study “may help clinicians make better decisions from multiple promising treatment regimens for patients with [extensive-stage]-SCLC by taking full consideration of their clinical benefits and toxicity profiles.”
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JAMA Netw Open 2020; 3: e2015748