1791P - Thoracic radiotherapy plus maintenance durvalumab after first-line carboplatin and etoposide plus durvalumab in extensive-stage disease small cell lung cancer (ED-SCLC): A multicenter single-arm open-label phase II trial (SAKK 15/19)tle

Background

Extensive-stage disease small-cell lung cancer (ED-SCLC) is an aggressive tumour type, accounting for 10-15% of all lung cancers. The role of thoracic radiotherapy (TRT) in the era of immune checkpoint inhibitors (ICIs) remains controversial and has yet to be established.

Methods

The SAKK 15-19 study, is a national single-arm prospective phase II study aiming to assess the impact of adding consolidative TRT to standard first-line chemotherapy and ICI in ED-SCLC. Patients (pts) with confirmed ED-SCLC were enrolled to receive carboplatin AUC 5 day 1, etoposide 100 mg/m2 day 1-3 and durvalumab 1500 mg day 1 up to 4 cycles. Pts without progression received maintenance durvalumab 1500 mg monthly up to 2 years with and TRT 39 Gy in 13 fractions over 2.5 weeks within 5 weeks after completion of chemotherapy and ICI. Prophylactic whole brain radiation was allowed. The primary endpoint was 12 months progression-free rate (PFR), secondary endpoints were progression-free survival (PFS), response rate and overall survival (OS). Based on the Impower 133 and the Caspian trials, the primary endpoint PFR at 12 months was tested, null hypothesis of PFR at 12 months was ≤ 12.5% with H1 for the PFR at 12 months being ≥ 25%.

Results

A total of 46 pts, with PS ECOG 0-1 were enrolled. Seventeen (37%) had ECOG 0, 14 (30%) patients had asymptomatic brain metastases, 14 (30.4%) females, 2 (4.3%) patients were never smokers.I At 24 months follow up the 12 months PFS was 16.4% (95% CI, 7-28), mOS was 15.8 months (95% CI, 10.2 months -22.5 months) and mPFS was 6.4 months (95% CI 4.8 months – 7.2 months). Grade 3/4 treatment-related adverse events (TRAEs) occurred in 23.9% of the patients, 1 (2%) patient developed grade 4 neutropenic fever. The most common grade 4 were neutropenia (23.9%) and thrombocytopenia (8.4%). One (2%) patient had grade 5, sepsis, while TRT did not add any severe toxicity, grade 3-4.

Conclusions

TRT added to standard chemotherapy and ICI in ED-SCLC lead to similar 12 months PFS rate (16.5% vs 12.5%) vs control and a favourable mOS of 15.8 months compared to historical controls (Caspian and Impower 133) without increased in clinically severe TRAEs.

Clinical trial identification

SAKK 15-19.

Editorial acknowledgement

Legal entity responsible for the study

Swiss group for clinical cancer research (SAKK).

Funding

AstraZeneca.

Disclosure

A. Addeo: Financial Interests, Institutional, Advisory Board: BMS, AZD, Roche, Eli Lilly; Financial Interests, Personal, Advisory Board: Pfizer, Takeda, MSD; Financial Interests, Institutional, Invited Speaker: Novartis. N. Mach: Financial Interests, Institutional, Research Grant: Release Therapeutics; Financial Interests, Personal, Proprietary Information, Patent holder: MVX-ONCO 1 ; Financial Interests, Personal, Proprietary Information, patent holder: MVX-2, MyoPod. M. Joerger: Financial Interests, Institutional, Coordinating PI, Clinical study activity: Basilea, Bayer, BMS, Immunophotonics, MSD, Novartis, Roche; Financial Interests, Institutional, Other, Clinical study activity: DaiichySankyo; Financial Interests, Institutional, Local PI, Clinical study activity: Innomedica; Financial Interests, Institutional, Coordinating PI: Anaveon; Non-Financial Interests, Advisory Role: Novartis, AstraZeneca, Basilea, Bayer, BMS, Debiopharm, MSD, Roche, Sanofi. P.R. Froesch: Financial Interests, Personal, Advisory Board: Roche, Takeda, Sanofi, BMS; Financial Interests, Personal, Invited Speaker: Janssen; Financial Interests, Institutional, Advisory Board: MSD. D. König: Financial Interests, Institutional, Advisory Board: AstraZeneca, Amgen, Sanofi, MSD, Merck, PharmaMar, Novartis, MSD, AstraZeneca; Financial Interests, Institutional, Other, Support for attending meetings and/or travel: Roche, Amgen, Sanofi, Sanofi; Financial Interests, Institutional, Invited Speaker: Mirati, Amgen, Sanofi, Swiss Oncology in Motion. All other authors have declared no conflicts of interest.