IO/Chemo Associated With Higher Toxicity Risk in ES-SCLC

In patients with extensive-stage small cell lung cancer (ES-SCLC), treatment with immunotherapy and chemotherapy was associated with a worse risk of toxicity and the likelihood of treatment discontinuation, according to results from a meta-analysis published in Thoracic Cancer.

Findings from a meta-analysis indicated a higher risk of grade 3 to 5 adverse effects with immunotherapy compared with chemotherapy in small cell lung cancer.

Findings from the analysis indicated that immunotherapy-based treatment was associated with a higher risk of grade 3 to 5 adverse effects (AEs) compared with chemotherapy (Odds ratio [OR], 1.16; 95% CI, 1.01-1.35; P = .93). Additionally, patients treated with an immunotherapy-based regimen was associated with a higher risk of treatment-related adverse effects (TRAEs) leading to discontinuation (OR, 2.30; 95% CI, 1.17-4.54; P <.01).

The meta-analysis included phase 2 and 3 clinical trials assessing immune checkpoint inhibitors plus systemic chemotherapy in patients with treatment-naïve ES-SCLC that were published between June 15, 2008, to October 23, 2022.

Several types of selection criteria restricted investigators to choose trials with the following characteristics:

• Prospective phase 2 and 3 randomized controlled studies in patients with ES-SCLC,
• first-line treatment with immune checkpoint inhibitors and systemic chemotherapy compared with chemotherapy alone,
• and available data on any-grade TRAEs, grade 3 to 5 TRAEs, and discontinuation in relation to TRAEs.

Investigators identified a total of 4612 reports that had potential relevancy, of which 7 were selected by independent evaluation by several authors. A total of 6105 reports were not considered to be pertinent. The studies that were included had a low bias risk according to each independent author’s review.

The meta-analysis included the following studies:

1. The phase 3 ASTRUM005 study (NCT04063163) assessing serplulimab plus carboplatin/etoposide vs chemotherapy alone;
2. the phase 3 CAPSTONE-1 study (NCT03711305) assessing adebrelimab plus platinum/etoposide vs chemotherapy alone;
3. the phase 3 CASPIAN study (NCT03043872) assessing durvalumab (Imfinzi) with or without tremelimumab (Imjudo) plus platinum-based chemotherapy vs chemotherapy alone;
4. the phase 3 IMPOWER133 study (NCT02763579) assessing atezolizumab (Tecentriq) plus carboplatin/etoposide vs chemotherapy alone;
5. the phase 3 KEYNOTE-604 study (NCT03066778) assessing pembrolizumab (Keytruda) plus platinum/etoposide vs chemotherapy alone;
6. a phase 2 study (NCT00527735) assessing ipilimumab (Yervoy) plus carboplatin/paclitaxel vs chemotherapy alone;
7. and a phase 3 study (NCT01450761) assessing ipilimumab plus platinum/etoposide vs chemotherapy alone.

Additional data from the study indicated that immunotherapy-based treatment was also associated with a higher risk of developing any-grade TRAEs (OR, 1.63; 95% CI, 1.31-2.03; P = .86). Investigators did not observe any difference in grade 5 TRAEs among patients who received first-line immunotherapy-based treatment and chemotherapy alone (OR, 1.56; 95% CI, 0.93-2.63; P = .79).

Reference

Longo V, Rizzo A, Catino A, et al. Safety evaluation of immune checkpoint inhibitors combined with chemotherapy for the treatment of small cell lung cancer: a meta-analysis of randomized controlled trials. Thoracic Can. Published online March 3, 2023. doi:10.1111/1759-7714.14842