John Kuruvilla, MD of the Princess Margaret Cancer Centre and the University of Toronto speaks about ASH 2020 abstract – 374 Effect of Pembrolizumab Monotherapy Versus Brentuximab Vedotin (BV) on Symptoms Associated with Health-Related Quality of Life (HRQoL) in Relapsed/Refractory (R/R) Classical Hodgkin Lymphoma (cHL) in the Randomized, Phase 3, Keynote-204 Study.
Introducing:
There is a lack of patient-reported results (PROs) in cHL, particularly those gathered prospectively in clinical trials. In addition, patients (pts) with cHL may experience B symptoms that can lead to decreased HRQoL, such as fever, night sweats, and weight loss. An open-label, international, randomized, phase 3 trial, KEYNOTE-204 (NCT02684292), found that the PD-1 inhibitor pembrolizumab showed statistically significant and clinically significant improvement in progression-free survival (PFS) vs. BV in R/R cHL pts. KEYNOTE-204’s current review examined PROs associated with R/R cHL symptoms (i.e. fatigue, nausea/vomiting, and pain) b.
Methods:
They were qualified for both BV-naive and BV-exposed pts. Pts were randomized 1:1 every 3 weeks (Q3W) or BV 1.8 mg/kg IV Q3W to pembrolizumab 200 mg intravenously (IV) and were stratified by previous auto-SCT (yes vs no) and first-line therapy status (primary refractory vs relapsed <12 months vs relapsed <12 months after the end of first-line therapy). The symptoms associated with cHL were assessed using symptom scales from the EORTC QLQ-C30 instrument as protocol-specified exploratory endpoints. Up until week 24 and every 12 weeks thereafter, EORTC QLQ-C30 was applied electronically at baseline and every 6 weeks. Higher scores showed worse symptoms on the EORTC QLQ-C30 symptom scales. Pts who obtained about 1 dose of research treatment and completed about 1 HRQoL evaluation were included in the analysis population. Prior to the commencement date of the study drug, both HRQoL and B-symptom data were obtained. Using the Kaplan-Meier process, time to first B symptoms were calculated, and treatment disparities were analyzed using a proportional hazards model of stratified Cox. The rate of B-symptom resolution was assessed using the Mantel-Haenszel relative risk test.
Outcomes:
The PRO review comprised 296 out of 304 randomized pts (pembrolizumab, 146; BV, 150). For both classes, enforcement rates at baseline were >90 percent and remained strong at week 24 (>80 percent). Mean (SD) baseline EORTC QLQ-C30 exhaustion, nausea/vomiting and pain scores were 34.9 (24.2), 4.0 (10.3), and 24.6 (25.6) for the pembrolizumab group and 35.3 (25.6), 8.8 (20.0) and 24.3 (27.5) for the BV group respectively. The mean baseline (SD) EORTC QLQ-C30 exhaustion, nausea/vomiting and pain scores at week 24 were 21.8 (20.8), 3.6 (10.1) and 12.5 (18.9) for the pembrolizumab group and 31.4 (17.2), 5.9 (14.0) and 17.4 (20.7) for the BV group respectively. Improvements in pembrolizumab fatigue and pain scores were observed at week 6 and remained stable until week 48; BV showed a stable impact up to week 48. No variations in nausea/vomiting score for pembrolizumab and BV were observed over time. 78 (pembrolizumab, 42; BV, 36) of the 300 pts treated had B symptoms at baseline. Among those 78 pts, 33 (42.3%), 63 (80.8%), and 26 (33.3%) had a fever, night sweats, and weight loss, respectively. Of the pts that did not experience B symptoms at baseline, 10/106 (9.4%) had symptoms during care in the pembrolizumab group and 14/116 (12.1%) in the BV group; in either group, the median period to first B symptom was not reached (hazard ratio 0.44 [95% CI 0.18-1.04]; two-sided P=0.062). 40/42 (95.2 percent) in the pembrolizumab group and 27/36 (75.0 percent) in the BV group experienced symptom resolution during the study (risk ratio 1.27 [95 percent CI 1.05-1.52]; two-sided P=0.013) for pts who had B symptoms at baseline.
The Conclusion:
Pembrolizumab monotherapy in pts with R/R cHL showed early and persistent improvement over BV in HRQoL fatigue and cHL-associated pain metrics that were stable over time, while both pembrolizumab and BV had stable nausea/vomiting measure over time. In addition, in pembrolizumab vs BV-treated pts, B symptoms were more likely to resolve. Taken together these results and clinically relevant changes in PFS support pembrolizumab as a preferred treatment choice for pts whose disease relapses after auto-SCT or for which auto-SCT is not available.