Characteristics of long-term survivors in the CASPIAN trial

Long-term survivors in the CASPIAN trial share common favourable – and potentially predictive – clinical and molecular characteristics. This was demonstrated in a subanalysis of the phase 3 trial investigating durvalumab in extensive-stage small cell lung cancer (ES-SCLC).

Recently, the phase 3 CASPIAN trial (NCT03043872) demonstrated improved overall survival (OS) with durvalumab plus platinum-etoposide (EP) versus EP alone as first-line treatment of ES-SCLC [1,2]. A numerical improvement in OS was observed with durvalumab plus tremelimumab plus EP versus EP alone. This benefit was sustained with more than 3 years follow-up [3]. As biomarkers that predict the efficacy of immune checkpoint blockade have not been well characterised in SCLC, clinical and molecular characteristics of patients who experienced long-term survival in CASPIAN were assessed. Dr Niels Reinmuth (Asklepios Lung Clinic, Germany) presented the results [4].

In CASPIAN, 805 patients with treatment-naïve ES-SCLC were randomised 1:1:1 to durvalumab/EP (every 3 weeks), durvalumab/tremelimumab/EP (every 3 weeks), or EP alone (every 3 weeks, 6 cycles). Participants in the immunotherapy arms received 4 cycles of durvalumab/EP or durvalumab/tremelimumab/EP, followed by maintenance durvalumab. The primary endpoints were OS for durvalumab/EP versus EP and for durvalumab/tremelimumab/EP versus EP. In post-hoc analyses, clinical characteristics were assessed in long-term survivors, defined as participants still alive at the data cut-off (median follow-up of 39.4 months). There were 44 (16%), 37 (14%), and 13 (5%) long-term survivors in the durvalumab/EP, durvalumab/tremelimumab/EP, and EP arms, respectively. PD-L1 expression and tissue tumour mutational burden (tTMB) were assessed in the biomarker-evaluable population at 18 and 36 months.

Objective response rate (ORR) and 24-month progression-free survival (PFS) rate was higher for long-term survivors compared with the intention-to-treat population in both the durvalumab/EP and durvalumab/tremelimumab/EP arms (ORR: 89% vs 79% and 92% vs 74%, respectively; PFS rate: 65% vs 11% and 67% vs 12%, respectively). Long-term survivors had a slightly higher incidence of favourable prognostic factors at baseline: incidence of brain/liver metastases was lower among long-term survivors versus the intention-to-treat population, although they still occurred in some long-term survivors (n=7 in durvalumab/EP, n=8 in durvalumab/tremelimumab/EP). More long-term survivors received 4 cycles of EP than the intention-to-treat population, with a higher median overall treatment exposure in the immunotherapy arms. In the durvalumab/tremelimumab/EP arm only, incidence of PD-L1 TC ≥1% (but not tTMB >10 mut/Mb) was higher in patients with OS ≥36 months versus OS <36 months (57% vs 31%). In addition, in the durvalumab/tremelimumab/EP arm, presence of HLA-DQB1*03:01 was higher in patients with OS ≥36 months versus <36 months (68% vs 36%).

Despite longer exposure, long-term survivors did not experience an increase in serious adverse events versus the intention-to-treat population. In addition, the distribution of serious adverse events across organ systems was similar in long-term survivors and the intention-to-treat population.

In summary, long-term survivors were more likely to have favourable prognostic characteristics than the intention-to-treat population. Most long-term survivors completed EP induction, had substantially greater overall treatment exposure, and achieved higher ORR and longer PFS versus the intention-to-treat population. Further investigation is warranted to understand the potential predictive role of biomarkers.

1. Paz-Ares L, et al. 2019;394:1929–1939.
2. Goldman JW, et al. Lancet Oncol. 2021;22:51–65.
3. Paz-Ares L, et al. Abstract LBA61. ESMO Congress 2021, 16–21 September.
4. Reinmuth N, et al. Durvalumab (D) ± tremelimumab (T) + platinum-etoposide (EP) in 1L extensive-stage (ES) SCLC: Characteristics of long-term survivors in the CASPIAN study. Abstract 141O. ELCC 2022 Virtual Meeting, 30 March–02 April.

 

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Posted on 25 May, 2022