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Durvalumab Plus Chemotherapy: New Option for Extensive-Stage SCLC


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The addition of the immune checkpoint inhibitor durvalumab to standard therapy significantly improved overall survival vs standard therapy alone for patients with previously untreated extensive-stage small cell lung cancer (SCLC), according to a preplanned interim analysis of the phase III CASPIAN study. These findings were reported at the 2019 International Association for the Study of Lung Cancer (IASLC) World Conference on Lung Cancer (WCLC) meeting.1

Patients who were randomly assigned to receive durvalumab had a 27% improvement in overall survival compared with patients randomly assigned to receive chemotherapy alone (13 vs 10.3 months, respectively, P = .0047). At 18 months, 33.9% of patients treated with durvalumab were alive, compared with 24.7% of those who received chemotherapy alone. Secondary endpoints of progression-free survival and response rates were also improved with the addition of durvalumab.

Luis Paz-Ares, MD, PhD

Luis Paz-Ares, MD, PhD

“Extensive-stage SCLC is a recalcitrant disease associated with a median overall survival of around 10 months. Although the disease may be chemosensitive, relapses and early resistance are common. New treatments for this aggressive disease are sorely needed,” stated lead author Luis Paz-Ares, MD, PhD, Professor of Medicine at the Hospital Universitario 12 de Octubre, Madrid. “In this analysis of the CASPIAN trial, the addition of durvalumab to etoposide/platinum as first-line treatment improved overall survival by 27%. Of note, this chemoimmunotherapy offers flexibility in choice of platinum, reflecting current clinical practice for this challenging disease.”

Dr. Paz-Ares continued: “CASPIAN met the primary endpoint of prolonging survival compared with a robust control arm that allowed for up to 6 courses of etoposide/platinum plus prophylactic cranial irradiation when indicated. Combining durvalumab with either cisplatin or carboplatin plus etoposide in extensive-stage SCLC provides an important new treatment option for patients and physicians.”

Approximately 70% of patients with SCLC present with extensive disease. Platinum-based chemotherapy has been the mainstay of treatment, and over the past few years, activity has been seen with immune checkpoint inhibitors. “We hypothesized that the combination of chemotherapy and immune checkpoint therapy could be an attractive first-line option,” Dr. Paz-Ares told listeners.

“CASPIAN met the primary endpoint of prolonging survival compared with a robust control arm that allowed for up to 6 courses of etoposide/platinum plus prophylactic cranial irradiation when indicated.”
— Luis Paz-Ares, MD, PhD

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Study Details

The open-label, randomized, phase III CASPIAN trial randomly assigned 537 patients with untreated extensive-stage SCLC to receive either durvalumab (an anti–PD-1 [programmed cell death protein 1] immune checkpoint inhibitor) plus etoposide/platinum or etoposide/platinum alone. A third arm evaluated durvalumab plus tremelimumab (an anti–CTLA-4 [cytotoxic T-lymphocyte–associated protein 4] checkpoint inhibitor) in addition to chemotherapy, but the results for this arm are not yet available. At the WCLC, Dr. Paz-Ares focused on the comparison between the durvalumab/chemotherapy arm vs etoposide/platinum alone.

Patients in the durvalumab arm (n = 268) were treated with up to 4 cycles of etoposide/platinum, followed by maintenance durvalumab until disease progression. Those randomly assigned to etoposide/platinum (n = 269) received up to 6 cycles of therapy plus prophylactic cranial irradiation at the investigator’s discretion. Across all treatment arms, investigators could opt for cisplatin or carboplatin, which was a stratification factor for the analysis.

The combination of durvalumab plus tremelimumab is being studied in non–small cell lung cancer as well as in other solid tumors. Theoretically, the combination may have improved antitumor activity over that observed with durvalumab alone. Results from CASPIAN for this arm will be presented in the future.

Key Findings

At baseline, demographic and disease characteristics were similar between both treatment arms. The median age of patients was 63 years; about 70% were male; about 45% were current smokers and 47% had any history of smoking; 10% had brain metastasis.

The 12-month overall survival rate was 53.7% in the durvalumab arm and 39.8% with chemotherapy alone; the 18-month overall survival rate was 33.9% and 24.7%, respectively. A consistent benefit for durvalumab was observed across subgroups. The rate of 12-month progression-free survival was 17.9% vs 4.7%, respectively—a large advantage favoring durvalumab.

The objective response rate was 67.9% for the durvalumab arm vs 57.6% for chemotherapy alone. The median duration of response was identical between the two treatment arms (5.1 months). The 12-month response rates were 22.7% with durvalumab added to chemotherapy and 6.3% with chemo­therapy alone.

Toxicity

No new safety signals related to drug therapy emerged at the interim analysis. The incidence of any adverse event was 98.1% for durvalumab plus chemotherapy vs 97% for chemotherapy alone. The incidence of grades 3 and 4 adverse events was similar between the two arms: 61.5% for immunotherapy vs 62.4% for chemotherapy alone.

As would be expected, immune-related adverse events were more frequent in the durvalumab arm: 20% (5% severe and 15% due to thyroid dysfunction) vs 2.6% for chemotherapy alone. The rate of adverse events leading to treatment discontinuation was identical for both arms: 9.4%. Hematologic toxicities were more frequent in the chemotherapy arm. The durvalumab/tremelimumab and etoposide/platinum arm is blinded until the final analysis. 

DISCLOSURE: Dr. Paz-Ares has consulted for AstraZeneca, Bristol-Myers Squibb, Merck Sharpe & Dohme, Pfizer, Roche, Lilly, Boehringer Ingelheim, Novartis, and Ariad.

REFERENCE

1. Paz-Ares L, et al: 2019 World Conference on Lung Cancer. Abstract PL02.11. Presented September 9, 2019.

 


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