The impact of staging by positron emission tomography (PET) on overall survival (OS) and progression-free survival (PFS) in the phase III PROCLAIM study

Background

Real-world evidence of the significant impact of PET staging on survival outcomes because of stage migration (upstaging) has been previously documented. However, the effect of stage migration as a result of PET has rarely been measured in randomized trials in the locally advanced (stage IIIA/B) setting. Here, we report the results from post-hoc subgroup analyses based on PET scan use in non-small cell lung cancer (NSCLC) patients in the PROCLAIM study.

Methods

The intent-to-treat (ITT) population of 598 patients with stage IIIA/B nonsquamous NSCLC were randomized to either pemetrexed (Pem) plus cisplatin (Cis) and concurrent radiotherapy (RT) for 3 cycles, followed by 4 cycles of Pem consolidation, or etoposide plus Cis and concurrent RT for 2 cycles, followed by a consolidation platinum-based doublet regimen for up to 2 cycles. PET scan (yes vs no) was one of the stratification factors since its use was not required per protocol. Subgroup analyses (yes vs no PET) of OS and PFS were conducted on the ITT population regardless of treatment since the study did not demonstrate superior efficacy for either arm. Kaplan-Meier methods and Cox regression models were used to estimate hazard ratios.

Results

Of the 598 patients, the majority (n = 491; 82.1%) had PET scan staging performed. The OS and PFS by PET scan use are presented in the table. In addition, results of subgroup analyses for each treatment arm were consistent with those of the ITT population.

PFS and OS by PET Use

CI, confidence interval; HR, hazard ratio; N, number of patients

Conclusions

Both a significantly improved PFS and a numerically longer OS in the subgroup of patients with PET scans, compared to patients with conventional staging, are consistent with improved survival due to stage migration. The magnitude of differences in OS and PFS based on PET is a reminder of the potential for factors other than the therapeutic intervention to affect outcomes.

Clinical trial identification

NCT00686959

Legal entity responsible for the study

Eli Lilly and Company

Funding

Eli Lilly and Company

Disclosure

N. Iscoe: Employee of Eli Lilly Canada Inc. R. Govindan: Boehringer Ingelheim, GSK, Celgene, Roche, Bayer, Genentech, Clovis, Helsinn Healthcare, Baxalta, Astellas, ARAID Pharmaceuticals. A.M. Hossain: Employed by Eli Lilly and Company. B. San Antonio, N. Chouaki: Employee of Eli Lilly and Company.

E. Vokes: Amgen, AstraZeneca, Boehringer Ingelheim, Celgene, Lilly, Genentech, Merck, Synta, VentiRx.

S. Senan: Lilly, Varian Medical Systems. All other authors have declared no conflicts of interest.