Durvalumab, with or without tremelimumab, plus platinum-etoposide in first-line treatment of extensive-stage small-cell lung cancer: 3-year overall survival update from CASPIAN*

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Abstract

Background

In the phase III CASPIAN study, first-line durvalumab in combination with etoposide plus either cisplatin or carboplatin (EP) significantly improved overall survival (OS) versus EP alone in extensive-stage small-cell lung cancer (ES-SCLC). Durvalumab plus tremelimumab plus EP numerically improved OS versus EP, but did not reach statistical significance. Here we report updated OS in censored patients after median follow-up of >3 years.

Patients and methods

805 patients with treatment-naïve ES-SCLC were randomized 1 : 1 : 1 to durvalumab plus EP, durvalumab plus tremelimumab plus EP, or EP. The two primary endpoints were OS for durvalumab plus EP versus EP and for durvalumab plus tremelimumab plus EP versus EP.

Results

As of 22 March 2021 (median follow-up 39.4 months, 86% maturity), durvalumab plus EP continued to demonstrate improved OS versus EP: hazard ratio (HR) 0.71 [95% confidence interval (CI) 0.60-0.86; nominal P = 0.0003]; median OS was 12.9 versus 10.5 months, and 36-month OS rate was 17.6% versus 5.8%. Durvalumab plus tremelimumab plus EP continued to numerically improve OS versus EP: HR 0.81 (95% CI: 0.67-0.97; nominal P = 0.0200); median OS was 10.4 months, and 36-month OS rate was 15.3%. Twenty-seven and nineteen patients in the durvalumab plus EP and durvalumab plus tremelimumab plus EP arms, respectively, remained on durvalumab treatment at data cut-off.

Conclusions

Three times more patients were estimated to be alive at 3 years when treated with durvalumab plus EP versus EP, with the majority still receiving durvalumab at data cut-off, further establishing durvalumab plus EP as first-line standard of care for ES-SCLC.

Highlights

•

Durvalumab plus EP showed sustained OS benefit over EP with a well-tolerated safety profile after median follow-up >3 years.
•

Three times more patients were estimated to be alive at 3 years when treated with durvalumab plus EP versus EP alone.
•

These results further establish durvalumab plus EP as standard of care for first-line treatment of patients with ES-SCLC.

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Most cited references 14

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First-Line Atezolizumab plus Chemotherapy in Extensive-Stage Small-Cell Lung Cancer

Leora Horn, Aaron Mansfield, Aleksandra Szczęsna … (2018)

Enhancing tumor-specific T-cell immunity by inhibiting programmed death ligand 1 (PD-L1)-programmed death 1 (PD-1) signaling has shown promise in the treatment of extensive-stage small-cell lung cancer. Combining checkpoint inhibition with cytotoxic chemotherapy may have a synergistic effect and improve efficacy.

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Durvalumab plus platinum–etoposide versus platinum–etoposide in first-line treatment of extensive-stage small-cell lung cancer (CASPIAN): a randomised, controlled, open-label, phase 3 trial

Luis Paz-Ares, Mikhail Dvorkin, Yuanbin Chen … (2019)

Most patients with small-cell lung cancer (SCLC) have extensive-stage disease at presentation, and prognosis remains poor. Recently, immunotherapy has demonstrated clinical activity in extensive-stage SCLC (ES-SCLC). The CASPIAN trial assessed durvalumab, with or without tremelimumab, in combination with etoposide plus either cisplatin or carboplatin (platinum-etoposide) in treatment-naive patients with ES-SCLC.

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Five-Year Overall Survival for Patients With Advanced Non‒Small-Cell Lung Cancer Treated With Pembrolizumab: Results From the Phase I KEYNOTE-001 Study

Edward Garon, Matthew Hellmann, Naiyer A Rizvi … (2019)

PURPOSE Pembrolizumab monotherapy has demonstrated durable antitumor activity in advanced programmed death ligand 1 (PD-L1)–expressing non‒small-cell lung cancer (NSCLC). We report 5-year outcomes from the phase Ib KEYNOTE-001 study. These data provide the longest efficacy and safety follow-up for patients with NSCLC treated with pembrolizumab monotherapy. PATIENTS AND METHODS Eligible patients had confirmed locally advanced/metastatic NSCLC and provided a contemporaneous tumor sample for PD-L1 evaluation by immunohistochemistry using the 22C3 antibody. Patients received intravenous pembrolizumab 2 mg/kg every 3 weeks or 10 mg/kg every 2 or 3 weeks. Investigators assessed response per immune-related response criteria. The primary efficacy end point was objective response rate. Overall survival (OS) and duration of response were secondary end points. RESULTS We enrolled 101 treatment-naive and 449 previously treated patients. Median follow-up was 60.6 months (range, 51.8 to 77.9 months). At data cutoff—November 5, 2018—450 patients (82%) had died. Median OS was 22.3 months (95% CI, 17.1 to 32.3 months) in treatment-naive patients and 10.5 months (95% CI, 8.6 to 13.2 months) in previously treated patients. Estimated 5-year OS was 23.2% for treatment-naive patients and 15.5% for previously treated patients. In patients with a PD-L1 tumor proportion score of 50% or greater, 5-year OS was 29.6% and 25.0% in treatment-naive and previously treated patients, respectively. Compared with analysis at 3 years, only three new-onset treatment-related grade 3 adverse events occurred (hypertension, glucose intolerance, and hypersensitivity reaction, all resolved). No late-onset grade 4 or 5 treatment-related adverse events occurred. CONCLUSION Pembrolizumab monotherapy provided durable antitumor activity and high 5-year OS rates in patients with treatment-naive or previously treated advanced NSCLC. Of note, the 5-year OS rate exceeded 25% among patients with a PD-L1 tumor proportion score of 50% or greater. Pembrolizumab had a tolerable long-term safety profile with little evidence of late-onset or new toxicity.

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Author and article information

Contributors

L. Paz-Ares

Journal

Journal ID (nlm-ta): ESMO Open

Journal ID (iso-abbrev): ESMO Open

Title: ESMO Open

Publisher: Elsevier

ISSN (Electronic): 2059-7029

Publication date PMC-release: 10 March 2022

Publication date Collection: April 2022

Publication date (Electronic): 10 March 2022

Volume: 7

Issue: 2

Electronic Location Identifier: 100408

Affiliations

[1 ]Hospital Universitario 12 de Octubre, H12O-CNIO Lung Cancer Unit, Universidad Complutense and Ciberonc, Madrid, Spain

[2 ]Cancer & Hematology Centers of Western Michigan, Grand Rapids, USA

[3 ]Asklepios Lung Clinic, Munich-Gauting, Germany

[4 ]Okayama University Hospital, Okayama, Japan

[5 ]Odessa Regional Oncological Dispensary, Odessa, Ukraine

[6 ]Omsk Regional Cancer Center, Omsk, Russian Federation

[7 ]Karl Landsteiner Institute of Lung Research and Pulmonary Oncology, Krankenhaus Nord, Vienna, Austria

[8 ]Istanbul University−Cerrahpaşa, Cerrahpaşa School of Medicine, Istanbul, Turkey

[9 ]Samsung Changwon Hospital, Sungkyunkwan University School of Medicine, Changwon, South Korea

[10 ]Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy

[11 ]The University of Chicago Department of Medicine, Section of Hematology/Oncology, Chicago, USA

[12 ]Kyiv City Clinical Oncological Centre, Kyiv, Ukraine

[13 ]Petrov Research Institute of Oncology, St Petersburg, Russian Federation

[14 ]AO Ospedali Riuniti PO Vincenzo Cervello, Palermo, Italy

[15 ]Thomayer Hospital, First Faculty of Medicine, Charles University, Prague, Czech Republic

[16 ]Dnipropetrovsk Medical Academy, Dnipro, Ukraine

[17 ]Semmelweis University, Budapest, Hungary

[18 ]Medical Oncology, UMHAT St Marina, Varna, Bulgaria

[19 ]AstraZeneca, Cambridge, UK

[20 ]AstraZeneca, Gaithersburg USA

[21 ]David Geffen School of Medicine at UCLA, Los Angeles, USA

Author notes

[∗ ]Correspondence to: Dr Luis Paz-Ares, Department of Medical Oncology, Hospital Universitario 12 de Octubre, Avenida de Córdoba, Madrid 28041, Spain. Tel: +34-91-390-8783/8349 lpazaresr@ 123456seom.org

[*]

Note: These data were presented as a mini oral presentation at the recent European Society for Medical Oncology (ESMO) Annual Meeting, 16-21 September 2021.

Article

Publisher Item ID: S2059-7029(22)00029-1 Publisher ID: 100408

DOI: 10.1016/j.esmoop.2022.100408

PMC ID: 9161394

PubMed ID: 35279527

SO-VID: d6fe5d13-9335-4616-8fa2-9ceece3f614c

License:

This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Durvalumab, with or without tremelimumab, plus platinum-etoposide in first-line treatment of extensive-stage small-cell lung cancer: 3-year overall survival update from CASPIAN*

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Abstract

Background

Patients and methods

Results

Conclusions

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Most cited references 14

First-Line Atezolizumab plus Chemotherapy in Extensive-Stage Small-Cell Lung Cancer

Durvalumab plus platinum–etoposide versus platinum–etoposide in first-line treatment of extensive-stage small-cell lung cancer (CASPIAN): a randomised, controlled, open-label, phase 3 trial

Five-Year Overall Survival for Patients With Advanced Non‒Small-Cell Lung Cancer Treated With Pembrolizumab: Results From the Phase I KEYNOTE-001 Study

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