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A 2-pronged approach in the non–small cell lung cancer (NSCLC) space that includes evaluating patient therapeutic outcomes via Response Evaluation Criteria in Solid Tumors (RECIST) for clinical trials and clinician-anchored approaches in observational studies can better serve future research purposes vs each individual method, experts have concluded in a new study published in JAMA Network Open.1
Data are lacking on how RECIST- and clinician-based end points might be used to bolster confidence in each other in regard to response- and progression-based measures, with particular weight placed on the ability of observational end points to be interpreted in the context of clinical trial response. Patient-level data from the IMpower 132 trial (conducted April 7, 2016, to May 31, 2017) and the nationwide Flatiron Health electronic health record (HER)-derived deidentified advanced NSCLC (advNSCLC) database (data collected January 1, 2011, to March 31, 2022) were used for the present analysis. IMpower 132 evaluated atezolizumab plus platinum-based chemotherapy of carboplatin or cisplatin plus pemetrexed vs carboplatin or cisplatin and pemetrexed in chemotherapy-naïve patients who have stage IV NSCLC.2
“Fundamental differences exist between methods used in clinical trials and routine clinical care to determine response and progression in patients with solid tumors,” the study authors wrote. "Further exploration of replicating RECIST end points using clinician-documented end points can further inform and increase confidence in the use of these outcome variables.”
There were 769 patients in this analysis; IMpower 132 inclusion/exclusion criteria were used to select patients for the observational cohort, and then all patients were randomized to first-line carboplatin or first-line cisplatin and pemetrexed. Main outcomes of interest were response rates, duration of response, and progression-free survival. Patients in the observational cohort (n = 494) were slightly older than patients in the trial cohort (n = 275), at a median (IQR) of 67 (60-74) years vs 63 (56-68) years and this group had more female patients (46.2% vs 32.7%). Most patients in each group were White (71.3% and 70.5%, respectively).
Clinical trial and electronic health record data were used this this analysis of the comparability of patient outcomes in the NSCLC space between clinical trial data and clinician assessments | Image Credit: ipopba-stock.adobe.com
Overall, there were more response assessments seen for the trial patients vs the observational patients, but the 3 principal outcomes were comparable between the groups. More of the patients in the observational cohort had an ECOG performance status score of 1, meaning they were ambulatory but had some physical restrictions.3Mean (SD) follow-up was longer in the observational cohort vs the trial cohort, 17.9 (19.7) months vs 15.8 (11.7) months, but there were fewer in the former group with at least 1 response assessment vs the latter group: 77.6% vs 93.1%. The patients in the observation cohort also had a higher percentage of patients with progressive disease: 17.8% vs 12.9%.
For platinum-based chemotherapy, there were significant differences in receipt of carboplatin plus pemetrexed as first-line induction therapy vs cisplatin plus pemetrexed:
Also, 54.9% of patients in the trial group received first-line maintenance therapy vs 32.8% of the observational group.
The unweighted OR was 1.28 (95% CI, 0.95-1.73), according to EHR data, while the weight OR was 1.09 (95% CI, 0.71-1.67) in the primary analysis, “suggesting comparable odds of response between the cohorts.”
The median EHR-derived duration of response was 5.59 months overall in the observational cohort vs 6.9 months in the trial cohort (HR, 1.12; 95% CI, 0.82-1.54). PFS measures were closer: 5.3 months vs 5.4 months (HR, 0.98; 955 CI, 0.81-1.19).
Sensitivity analyses determined that for all outcomes, the ORs of response were comparable between the trial and observational cohorts after weighting.
The study authors note that their findings are strong because they echo previous analyses,4,5 add new knowledge, and are robust in that no difference was observed between the trial duration of response and the EHR-derived duration of response.
Potential limitations on these findings are that the investigators could not apply all trial criteria to the observational cohort, that the observational cohort was missing data on race, ethnicity, and PD-L1 status, and that the patients treated in the trial had a strict response assessment protocol, whereas the patients in the observational group were assessed as part of their routine care with varying frequency.
“This study provides valuable insight into the relationships and methodological considerations for interpreting clinical outcomes between trial and observational cohorts,” the authors concluded. “The analytic approach could be extended to evaluate whether end points remain comparable in other disease settings.”
References
1. Lu Y, Langerman SS, McCain E, et al. Response- and progression-based end points in trial and observational cohorts of patients with NSCLC. JAMA Netw Open. 2024;7(5):e249286. doi:10.1001/jamanetworkopen.2024.9286
2. A study of atezolizumab in combination with carboplatin or cisplatin + pemetrexed compared with carboplatin or cisplatin + pemetrexed in participants who are chemotherapy-naive and have stage iv non-squamous non-small cell lung cancer (NSCLC) (IMpower 132). ClinicalTrials.gov. Updated November 21, 2023. Accessed May 8, 2024. https://www.clinicaltrials.gov/study/NCT02657434
3. ECOG performance status scale. ECOG-ACRIN Cancer Research Group. Accessed May 8, 2024. https://ecog-acrin.org/resources/ecog-performance-status/
4. Ton TGN, Pal N, Trinh H, et al. Replication of overall survival, progression-free survival, and overall response in chemotherapy arms of non-small cell lung cancer trials using real-world data. Clin Cancer Res. 2022;28(13):2844-2853. doi:10.1158/1078-0432.CCR-22-0471
5. Huang Bartlett C, Mardekian J, Cotter MJ, et al. Concordance of real-world versus conventional progression-free survival from a phase 3 trial of endocrine therapy as first-line treatment for metastatic breast cancer. PLoS One. 2020;15(4):e0227256. doi:10.1371/journal.pone.0227256