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Observational Study
. 2024 May 1;7(5):e249286.
doi: 10.1001/jamanetworkopen.2024.9286.

Response- and Progression-Based End Points in Trial and Observational Cohorts of Patients With NSCLC

Yichen Lu  1 , Spencer S Langerman  1 , Emily McCain  1 , Kelly Magee  1 , Sophia L Maund  2 , Minu K Srivastava  2 , Meghna Samant  1
Affiliations
Observational Study

Response- and Progression-Based End Points in Trial and Observational Cohorts of Patients With NSCLC

Yichen Lu et al. JAMA Netw Open. .

Abstract

Importance: Response Evaluation Criteria in Solid Tumors (RECIST) are commonly used to assess therapeutic response in clinical trials but not in routine care; thus, RECIST-based end points are difficult to include in observational studies. Clinician-anchored approaches for measuring clinical response have been validated but not widely compared with clinical trial data, limiting their use as evidence for clinical decision-making.

Objective: To compare response- and progression-based end points in clinical trial and observational cohorts of patients with non-small cell lung cancer (NSCLC).

Design, setting, and participants: This retrospective cohort study used patient-level data from the IMpower132 trial (conducted April 7, 2016, to May 31, 2017) and a nationwide electronic health record (EHR)-derived deidentified database (data collected January 1, 2011, to March 31, 2022). Patients in the observational cohort were selected according to the inclusion and exclusion criteria of the IMpower132 trial. All patients in the observational cohort had stage IV NSCLC.

Exposure: All patients were randomized to or received first-line carboplatin or cisplatin plus pemetrexed.

Main outcomes and measures: End points included response rates, duration of response, and progression-free survival, compared between the trial and observational cohorts before and after weighting. Response rates for the observational cohort were derived from the EHR.

Results: A total of 769 patients met inclusion criteria, 494 in the observational cohort (median [IQR] age, 67 [60-74] years; 228 [46.2%] female; 45 [9.1%] Black or African American; 352 [71.3%] White; 53 [10.7%] American Indian or Alaska Native, Asian, Hawaiian or Pacific Islander, or multiracial) and 275 in the trial cohort (median [IQR] age, 63 [56-68] years; 90 [32.7%] female; 4 [1.5%] Black or African American; 194 [70.5%] White; 65 [23.6%] American Indian or Alaska Native, Asian, Hawaiian or Pacific Islander, or multiracial). All 3 end points were comparable between the study cohorts. Trial patients had a higher number of response assessments compared with patients in the weighted observational cohort. The EHR-derived response rate was numerically higher than the objective response rate after weighting (100.3 of 249.3 [40.2%] vs 105 of 275 [38.2%]) due to higher rates of observed partial response than RECIST-based partial response. Among patients with at least 1 response assessment, the EHR-derived response rate remained higher than the objective response rate (100.3 of 193.4 [51.9%] vs 105 of 256 [41.0%]) due to a higher proportion of patients in the observational cohort with no response assessment.

Conclusions and relevance: In this study, response- and progression-based end points were similar between clinical trial and weighted observational cohorts, which increases confidence in the reliability of observational end points and can inform their interpretation in relation to trial end points. Additionally, the difference observed in response rates (including vs excluding patients with no response assessment) highlights the importance of future research adopting this 2-way approach when evaluating the relationship of EHR-derived and objective response rates.

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Conflict of interest statement

Conflict of Interest Disclosures: Ms Lu reported being employed by Flatiron Health, Inc, which is an independent member of the Roche Group; owning stock in Roche; and receiving nonfinancial (project management, data, and other study-related support) from Genentech during the conduct of the study. Mr Langerman reported being employed by Flatiron Health, Inc, which is an independent member of the Roche Group; owning stock in Roche; and receiving nonfinancial (project management, data, and other study-related support) from Genentech during the conduct of the study. Ms McCain reported being employed by Flatiron Health, Inc, which is an independent member of the Roche Group; owning stock in Roche; and receiving nonfinancial (project management, data, and other study-related support) from Genentech during the conduct of the study. Ms Magee reported being employed by Flatiron Health, Inc, which is an independent member of the Roche Group; owning stock in Roche; and receiving nonfinancial (project management, data, and other study-related support) from Genentech during the conduct of the study. Dr Maund reported being employed by and owning stock in Roche during the conduct of the study. Dr Srivastava reported being employed by and owning stock in Genentech/Roche outside the submitted work. Dr Samant reported being employed by Flatiron Health, Inc, which is an independent member of the Roche Group; owning stock in Roche; and receiving nonfinancial (project management, data, and other study-related support) from Genentech during the conduct of the study; being employed by Calico Life Sciences outside the submitted work; and owning stock in Flatiron Health outside the submitted work.

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