Abstract 1051P
Background
Preclinical and retrospective clinical studies have suggested that local RT enhances the activity of ICI mediated by the so called abscopal effect – a systemic response in metastatic cancer induced by local irradiation. The most recent prospective trials have not been able to support this hypothesis.
Methods
In this study we have included a total of 3’079 NSCLC patients with squamous and non-squamous histology from three phase-III trials that investigated the efficacy of atezolizumab in combination with different first-line chemotherapies or as second-line monotherapy. Contrary to earlier studies we have analyzed prior and on-study RT. To investigate the differences between various RT schedules (on-study), we divided the patients in three subgroups based on single-dose fraction: A ≤ 2 Gray (Gy), B > 2 Gy ≤ 5 Gy, C > 5 Gy. Overall survival (OS) and progression-free survival (PFS) were investigated using Kaplan-Meier estimates and Cox proportional hazard models. Nominal p-values were determined by log-rank tests. Overall response rate (ORR) estimates were calculated using the Clopper-Pearson method.
Results
Prior and on-study RT were not associated with prolonged OS (Table). We have also been unable to observe improvements in PFS and ORRs. In contrast, OS tended to be numerically worse [Intention-to-treat (ITT) populations of IMpower130: 14.0 vs 18.6 months, hazard ratio (HR) 1.23, p = 0.048; IMpower150: 15.0 vs 19.1 months, HR 1.18, p = 0.087; OAK 10.3 vs 12.0 months, HR 1.18, p = 0.023] with a comparable magnitude across the three trials. Patients receiving on-study RT (n = 213) showed an improved OS with single dose fractions > 5 Gy (19.2 vs 13.4 months, HR 0.60, p = 0.006). Table. Table: 1051P
| IMpower130 (n = 705) | IMpower150 (n = 1’187) | OAK (n = 1’187) | ||||||
| Arm Treatment | A ACNP | B CNP | A ACP | B ABCP | C BCP | A A | B D | |
| Prior RT | + - | OS 16.5 vs 19.2 HR 1.18, p = 0.211 | OS 12.0 vs 17.7 HR 1.38, p = 0.073 | OS 16.4 vs 20.5 HR 1.26, p = 0.179 | OS 19.1 vs 20.4 HR 1.14, p = 0.438 | OS 12.3 vs 16.4 HR 1.24, p = 0.167 | OS 12.1 vs 14.1 HR 1.28, p = 0.023 | OS 9.0 vs 10.9 HR 1.15, p = 0.186 |
| On-study RT | + | OS 18.1 vs 18.6 HR 0.99, p = 0.964 | OS 13.5 vs 15.9 HR 1.09, p = 0.692 | OS 11.1 vs 19.7 HR 1.33, p = 0.220 | OS 13.4 vs 20.4 HR 1.77, p = 0.083 | OS 14.0 vs. 15.2 HR 1.20, p = 0.583 | OS 15.1 vs 13.1 HR 0.95, p = 0.798 | OS 6.2 vs 10.3 HR 2.43, p = 0.003 |
| - |
OS in months A Atezolizumab, B Bevacizumab, C Carboplatin, P Paclitaxel, NP Nab-P, D Docetaxel # HR and p-values are stratified
Conclusions
We could not find any evidence for an abscopal effect leading to improved outcomes irrespective of the systemic treatment. Since RT increases toxicity, our results do not support the use of RT unless there is a clinical indication.
Clinical trial identification
IMpower130: NCT02367781; IMpower150: NCT02366143; OAK: NCT02008227.
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Kantonsspital Graubünden.
Disclosure
A. Meisel: Financial Interests, Personal, Advisory Board: Amgen, Astellas, Boehringer Ingelheim, BMS, Celgene, GSK, Janssen, Merck, MSD, Novartis, Roche, Sanofi, Servier, Takeda, Vifor; Financial Interests, Personal, Advisory Role: Gerresheimer; Financial Interests, Institutional, Funding: Merck & Cie; Financial Interests, Personal, Invited Speaker: Bayer; Financial Interests, Personal, Funding: Bayer; Financial Interests, Personal, Expert Testimony: Sanofi; Financial Interests, Personal, Other: Amgen, Boehringer Ingelheim, Janssen, Merck, Roche, Sanofi, Servier; Financial Interests, Personal, Writing Engagements: Astellas. M.T. Mark: Financial Interests, Personal, Advisory Board: AstraZeneca, BMS, Roche, MSD, Takeda; Financial Interests, Institutional, Funding: AstraZeneca. S.I. Rothschild: Financial Interests, Personal, Advisory Role: AstraZeneca, Boehringer Ingelheim, BMS, Eisai, Roche, Novartis, Merck Serono, MSD, Pfizer, Takeda, AbbVie; Financial Interests, Funding: Boehringer Ingelheim, AstraZeneca, BMS, Eisai, Merck Serono, AbbVie; Financial Interests, Personal, Expert Testimony: Roche, AstraZeneca, BMS. M.J. Hochmair: Financial Interests, Personal, Speaker’s Bureau: AstraZeneca, BMS, Boehringer Ingelheim, MSD, Roche, Takeda; Financial Interests, Personal, Advisory Board: AstraZeneca, BMS, Boehringer Ingelheim, MSD, Roche, Takeda. D.R. Gandara: Financial Interests, Funding: Amgen, AstraZeneca, Genentech, Merck, BMS; Financial Interests, Institutional, Advisory Board: AstraZeneca, Roche-Genentech, Guardant Health, IO Biotech, Oncocyte, BMS; Financial Interests, Personal, Other, Personal Fees: Inivata, Eli Lilly, Merck, Novartis. F. Cappuzzo: Financial Interests, Personal, Advisory Board: AstraZeneca, BMS, MSD, Roche, Takeda, Pfizer, Bayer. M. Reck: Financial Interests, Personal, Other, honoraria for lectures and consultancy: Amgen, AstraZeneca, BMS, Boehringer Ingelheim, MSD, Roche, Eli Lilly, Merck, Mirati, Novartis, Pfizer, Samsung Bioepis. F. Stenner-Liewen: Financial Interests, Personal, Advisory Board: AstraZeneca, Bayer, BMS, Janssen, MSD, Sanofi; Financial Interests, Personal, Other, Travel/Accommodation: BMS, Roche, Sanofi. R.A.F. von Moos: Financial Interests, Personal, Advisory Board: Amgen, AstraZeneca, BMS, GSK, Gilead, MSD, Roche, Pfizer, PharmaMar; Financial Interests, Personal, Writing Engagements: Vifor; Financial Interests, Personal, Speaker’s Bureau: Vifor; Financial Interests, Personal, Other, Educational events/lectures/presentations: Vifor. All other authors have declared no conflicts of interest.