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Results from TROG 02.01 demonstrated that adjuvant radiotherapy (RT) in high-risk melanoma patients is associated with improved locoregional control (LRC). The aim of our study is to evaluate the role of adjuvant RT in standard risk (SR), high risk (HR) and ultra-high risk (UHR) melanoma patients in the immunotherapy era. S1404 randomized resected stage III and stage IV melanoma patients to standard of care adjuvant immunotherapy or pembrolizumab after surgery. We retrospectively analyzed the data for 1239 patients enrolled in S1404. We stratified the patients according to SR (no high-risk features), HR (defined according to TROG 02.01 trial) and UHR (extracapsular extension with 5 or more positive nodes or 4 cm or greater nodal size). Recurrence free survival (RFS) and time to regional recurrence (TtRR) were primary outcomes; distant metastasis free survival (DMFS) was a secondary outcome. RFS was estimated using the Kaplan-Meier method and associations with the outcome were evaluated using Cox regression models. TtRR and DMFS were estimated with cumulative incidence curves and associations with the outcome were evaluated using cause-specific regression models. Of 1239 patients analyzed, 136 patients (11%) completed RT. The most common RT regimen used was 30 Gy/5 fractions (37%) followed by 48 Gy/20 fractions (31%). Fifty three percent of patients were HR per TROG02.01. More HR patients received RT compared to SR (16 % versus 6%; p-value <= 0.001). Among the patients who received RT 76/136 (56%) were advanced stage (Stage IIIC/ resected Stage IV) compared with those who did not 390/1103 (35%); p value <= 0.001. Similarly macroscopic lymph node involvement was significantly higher in RT group, 89/136 (65%) versus 457/1103 (41%); p value <=0.001. TtRR was significantly longer for patients who completed RT (all comers: 9% RR @ 4 year no RT vs 1% @ 4 year with RT; p value = 0.015). For high-risk patients, TtRR was longer for patients who received RT regardless of PD1 status (12% RR @ 4 year no RT vs 2% @ 4 year with RT; p value = 0.009). No significant difference in value of RT was seen based on anatomic nodal site, study arm or BRAF mutation status. Among patients treated with pembrolizumab, a trend toward RFS benefit was seen in patients treated with RT (HR = 1.54, 95% confidence interval 0.94-2.53; p=0.085). There was no significant difference in DMFS between those who completed RT versus not. Our study validated the results of previous studies and suggests consideration of adjuvant RT in high-risk patients regardless of planned adjuvant immunotherapy for improved LRC. We recommend the use of adjuvant RT in patients with macroscopic nodal involvement with extracapsular extension or with heavy nodal burden even in the immunotherapy era. [ABSTRACT FROM AUTHOR]

Background: Durability of response is a clinically relevant dimension of the treatment effect in randomized clinical trials; it is often measured by comparing among the responders the duration of response between the treatment arms. However, since the comparison groups are defined by response (a post-randomization event), it is subject to analysis-by-responder bias, especially if the proportion of responders differs between the arms. Methods: Two simple methods are developed that use tumor shrinkage measurements in order to lessen analysis-byresponder bias by generating more comparable patient subsets in the control and experimental arms of the trial. These subsets are then used to estimate between-arm differences in response duration. In the subtraction method, responding patients with the least tumor shrinkage in the treatment arm with more responders are removed from the patient subset for that arm. In the addition method, non-responding patients with the most tumor shrinkage in the treatment arm with fewer responders are added to the patient subset for that arm. In both methods, the numbers of patients subtracted or added are such that the proportion of patients in the modified patient subset is the same as the proportion of responders in the other treatment arm. Results: The methods are demonstrated on a hypothetical dataset where they are shown to eliminate analysis-by-responder bias and on two published analyses of randomized trials that compared the duration of response between the treatment arms. Conclusions: The proposed methods can lessen the analysis-by-responder bias. These methods to compare duration of response between treatment arms may provide a useful exploratory analysis to measure treatment efficacy among responders. [ABSTRACT FROM AUTHOR]

Although SCLC is an aggressive disease with poor historical outcomes, third-line (3L) nivolumab patients from the phase 1/2 trial CheckMate 032 had longer responses and better long-term survival vs historical comparison. Routine care survival, resource use, and costs were derived from patients receiving 3L treatment for SCLC in the SEER-Medicare registry. [Extracted from the article]