Few grade 3 or higher immune-related adverse events were observed with first-line durvalumab plus platinum-etoposide in patients with extensive-stage small cell lung cancer (ES-SCLC), according to findings from the safety analysis of the phase III CASPIAN study presented at the ESMO Immuno-Oncology Congress 2019 in Geneva, Switzerland (11-14 December).
Mustafa Özgüroğlu, Professor of Medical Oncology, Cerrahpaşa School of Medicine, Istanbul University−Cerrahpaşa in Istanbul, Turkey, presented results from analyses of safety, pharmacokinetics (PK), and immunogenecity from the open-label phase III CASPIAN (NCT03043872) study of first-line durvalumab plus platinum-etoposide (EP) compared to EP alone in patients with ES-SCLC.
Findings from the pre-planned interim analysis showed that durvalumab plus EP significantly improved overall survival (OS) as compared to EP alone in patients with ES-SCLC (hazard ratio [HR] 0.73; 95% confidence interval [CI], 0.59–0.91; p = 0.0047).
The rates of all-cause adverse events (AEs) as well as AEs leading to discontinuation were similar with both treatments, although serious AEs (SAEs) were numerically lower at 30.9% versus 36.1%, respectively, and immune-mediated AEs (imAEs) were higher with the addition of durvalumab to EP, prompting Prof. Özgüroğlu and co-investigators to further evaluate safety, PK, and immunogenicity, the study’s secondary endpoints.
CASPIAN enrolled treatment-naive patients with ES-SCLC and WHO performance status 0/1 that were randomised to treatment with EP plus durvalumab at 1500 mg every 3 weeks, or EP plus durvalumab at 1500 mg plus tremelimumab at 75 mg every 3 weeks, or to receive EP every 3 weeks. Investigator’s choice of carboplatin or cisplatin was allowed. In the immunotherapy arm patients were treated with 4 cycles of EP, followed by 1500 mg durvalumab every 4 weeks until progression; up to 6 cycles of EP and optional prophylactic cranial irradiation were permitted in the control EP arm.
No treatment-emergent anti-drug antibodies are elicited by durvalumab
At ESMO Immuno-Oncology Congress 2019, results from the 265 patients who were treated with durvalumab plus EP and the 266 control patients receiving EP were presented. The PK analysis showed that serum concentrations of durvalumab were within the expected range. PK profiles of EP components were similar across both arms. In the durvalumab/EP arm, 201 patients were evaluated for anti-drug antibodies (ADA); of these, 11 (5.5%) were positive for ADA to durvalumab at baseline only and no patients were positive for treatment-emergent ADA or neutralising antibodies.
The most common AEs, grade 3/4 AEs, and SAEs in both arms consisted of haematological toxicities, which were well managed using standard therapies per local practice. Fewer (50.4%) patients in the durvalumab/EP arm received colony stimulating factor compared to 56.9% with EP and 12.7% versus 20.8% of patients in the respective arms received blood transfusions. When events that coincided with cycles 5 and 6 of EP in the control arm were removed, the overall SAE rates were 30.9% for durvalumab/EP versus 30.1% for EP. Most imAEs were low grade endocrine-related AEs that were managed with corticosteroid or endocrine therapy.
Immune-mediated AE rates were low but more common with durvalumab
Any imAEs occurred in 52 (20%) patients on durvalumab/EP versus 7 (3%) of patients on EP; of these, 5% versus 1% were grade ≥3, respectively. The most commonly reported any grade imAEs with durvalumab/EP were hypothyroid (9%), hyperthyroid (5%), pneumonitis (3%), hepatic (3%), and 2% of patients each had dermatitis/rash, diarrhoea/colitis, thyroiditis, and type 1 diabetes. Grade ≥3 imAEs with durvalumab plus EP included pneumonitis (1%), hepatic (2%), diarrhoea/colitis (0.4%), and type 1 diabetes (2%). The earliest any grade imAE was diarrhoea/colitis, which was seen at median 28 days after receiving the first dose.
With EP alone, commonly reported any grade imAEs included hypothyroid (1%), pneumonitis (1%), and diarrhoea/colitis (0.4%); of these only Grade ≥3 pneumonitis (1%) was recorded. The first imAEs of dermatitis/rash occurred at a median 31 days.
The authors pointed out that the incidence of anti-drug antibodies to durvalumab was low and were seen only at baseline. They further remarked that the safety profile of durvalumab/EP was consistent with previous reports of both durvalumab and EP.
This trial was funded by Astra Zeneca.
LBA2 – Özgüroğlu M, Goldman JW, Reinmuth N, et al. First-line durvalumab plus platinum-etoposide in extensive-stage (ES)-SCLC: Safety, pharmacokinetics (PK) and immunogenicity in CASPIAN.