LBA58 - ORR in patients receiving nivolumab plus radiotherapy in advanced non-small cell lung cancer: First results from the FORCE trial

Background

The FORCE trial addressed the hypothesis that applying radiation together with anti-PD-1 immunotherapies may foster immune response, by combining nivolumab and radiation in non-small cell lung cancer (NSCLC) patients with clinical indication for radiotherapy.

Methods

From 02/17-12/19, 101 patients with stage IV non-squamous NSCLC in 2^nd-line or 3^rd-line treatment were enrolled in this multicentre, prospective, non-randomized phase II trial. 41 patients with a clinical indication for palliative radiotherapy received nivolumab 240 mg followed by 5 x 4 Gy on consecutive days to metastasis (53% bone, 18% lymph node, 29% other), initiated 72 hours after first nivolumab administration (Group A). 60 patients without an indication for radiotherapy received nivolumab only (Group B). Nivolumab was administered every two weeks in both groups and continued until progression or limiting toxicities. In both groups, biomaterials were collected systematically for exploratory hypothesis-generating analyses.

Results

Whilst some patient baseline characteristics, e.g. age, gender, smoking status and number of previous therapies were similar in both groups, preliminary analyses indicate an imbalance with a number of unfavourable characteristics being more prevalent in group A (e.g. ECOG 1, 81% vs 58%; extrathoracic metastases, 93% vs. 63%; p<0.05). Treatment related grade 3-4 adverse events occurred at similar rates in both groups (17% vs. 15%, p=0.8). The primary objective was to achieve an objective response rate (ORR) of > 19% per RECIST criteria 1.1 in group A. With an ORR of 8.3% in group A, this target was not met (p=0.991 for one-sided binomial test). ORR in group B was 23.8%. Patients with missing tumor response assessment due to tumor-related death (group A and B: 8 and 5) were considered non-responders.

Conclusions

The combination of nivolumab and palliative radiotherapy was safe and feasible; however, it did not improve ORR in the setting of this exploration. The requirement for a clinical indication for palliative radiotherapy enforced selection of patients with unfavourable properties into group A. Clinical characteristics need consideration when assessing the efficacy of immunotherapy.

Clinical trial identification

EudraCT Nr.: 2015-005741-3; NCT03044626.

Editorial acknowledgement

Legal entity responsible for the study

AIO-Studien gGmbH.

Funding

Bristol Myers Squibb.

Disclosure

F. Bozorgmehr: Research grant/Funding (self): BMS; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): AstraZeneca; Honoraria (self), Research grant/Funding (institution): Roche; Honoraria (self): Novartis; Honoraria (self): MSD; Honoraria (self): Chugai. A. Atmaca: Advisory/Consultancy: BMS; Advisory/Consultancy: Roche; Advisory/Consultancy: MSD; Advisory/Consultancy: AstraZeneca. M. Faehling: Honoraria (self), Advisory/Consultancy: BMS; Honoraria (self), Advisory/Consultancy: MSD; Honoraria (self), Advisory/Consultancy: Roche; Honoraria (self), Advisory/Consultancy: AstraZeneca. N. Reinmuth: Honoraria (self), Advisory/Consultancy: BMS. A. Stenzinger: Advisory/Consultancy, Speaker Bureau/Expert testimony: AstraZeneca; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution): Bayer; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (self): BMS; Advisory/Consultancy, Speaker Bureau/Expert testimony: Eli Lilly; Advisory/Consultancy, Speaker Bureau/Expert testimony: Illumina; Advisory/Consultancy, Speaker Bureau/Expert testimony: Janssen; Advisory/Consultancy, Speaker Bureau/Expert testimony: MSD; Advisory/Consultancy, Speaker Bureau/Expert testimony: Novartis; Advisory/Consultancy, Speaker Bureau/Expert testimony: Pfizer; Advisory/Consultancy, Speaker Bureau/Expert testimony: Roche; Advisory/Consultancy, Speaker Bureau/Expert testimony: Seattle Genetics; Advisory/Consultancy, Speaker Bureau/Expert testimony: Takeda; Advisory/Consultancy, Speaker Bureau/Expert testimony: ThermoFischer; Research grant/Funding (institution): Chugai. M. Thomas: Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: AstraZeneca; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: BMS; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Boehringer Ingelheim; Honoraria (self), Travel/Accommodation/Expenses: Celgene; Honoraria (self), Travel/Accommodation/Expenses: Chugai; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Lilly; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: MSD; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Novartis; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Pfizer; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Roche; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Takeda. All other authors have declared no conflicts of interest.