The following article features coverage from the IASLC 2019 World Conference on Lung Cancer meeting. Click here to read more of Cancer Therapy Advisor‘s conference coverage.

According to results presented at the IASLC 2019 World Conference on Lung Cancer hosted by the International Association for the Study of Lung Cancer held in Barcelona, Spain, addition of the programmed cell death-ligand 1 (PD-L1) inhibitor, durvalumab, to etoposide/platinum chemotherapy was associated with an overall survival (OS) benefit in treatment-naive patients with extensive-stage small cell lung cancer (ES-SCLC) compared with chemotherapy alone1,2

With a median OS of approximately 10 months for patients with ES-SCLC treated with etoposide/platinum chemotherapy — the standard of care in this disease in Western countries — there is an urgent need for more effective treatment approaches for these patients.

The 3-arm, open-label, randomized CASPIAN trial (ClinicalTrials.gov NCT03043872) evaluated etoposide in combination with either cisplatin or carboplatin with or without either durvalumab as a single-agent immune checkpoint inhibitor therapy or the combination of durvalumab with the cytotoxic T-lymphocyte–associated protein 4 (CTLA-4) inhibitor, tremelimumab, in previously untreated, adult patients with ES-SCLC randomly assigned in a 1:1:1 ratio to each of the treatment arms. Patients receiving immune checkpoint inhibitor therapy were also treated with maintenance durvalumab following a response to initial treatment, and those in the chemotherapy alone arm had the option of subsequent prophylactic cranial irradiation therapy. The primary end point of the study was OS.1,2

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In this interim analysis, only results for those patients assigned to chemotherapy with (268 patients) or without (269 patients) single-agent immune checkpoint inhibitor therapy with durvalumab were compared.

Results for the arm evaluating dual immune checkpoint inhibitor therapy plus chemotherapy remained blinded at the time of this analysis.

A key finding was a significant improvement in OS for patients receiving up to 4 cycles of durvalumab plus chemotherapy, with a median OS of 13.0 months compared with 10.3 months for those receiving up to 6 cycles of chemotherapy alone (hazard ratio [HR], 0.75, 95% CI, 0.591-0.909; P =.0047).

Notably, at 18 months, 33.9% in the durvalumab arm were alive compared with only 24.7% of those patients receiving chemotherapy alone. Significant improvements in progression-free survival and overall response rate were also observed with addition of durvalumab to etoposide/platinum chemotherapy.

While the incidence of grade 3/4 adverse events was close to 60% in the 2 study arms, less than 10% of patients in either arm discontinued treatment due to adverse events. More patients in the chemotherapy alone arm experienced hematological adverse events, although no new safety signals were observed in this study.

Luis Paz-Ares, MD, PhD, from Hospital Universitario, H120-CNIO Lung Cancer Unit, Universidad Complutense and Ciberonac, Madrid, Spain said in a statement that “the addition of durvalumab to etoposide/platinum as first-line treatment for extensive-stage non-small cell lung cancer significantly improved overall survival (27% reduction in risk of death) versus a robust control arm that permitted up to 6 cycles of etoposide. Of note, this chemo-immunotherapy regimen offers flexibility in platinum choice (carboplatin or cisplatin), reflecting current clinical practice for this challenging disease.”2

Read more of Cancer Therapy Advisor‘s coverage of the IASLC annual meeting by visiting the conference page.

References

  1. Paz-Ares L, Chen Y, Reinmuth N, et al. Overall survival with durvalumab plus etoposide-platinum in first-line extensive-stage SCLC: results from the CASPIAN study. Presented at: IASLC 2019 World Conference on Lung Cancer hosted by the International Association for the Study of Lung Cancer; September 7-10, 2019; Barcelona, Spain. Abstract PL02.11.
  2. International Association for the Study of Lung Cancer. Durvalumab combined with chemotherapy improves overall survival in patients with extensive stage small-cell lung cancer; first-line treatment reduced mortality risk by 27 percent. Published September 9, 2019. Accessed September 9, 2019.