In:
Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 40, No. 16_suppl ( 2022-06-01), p. 9548-9548
Kurzfassung:
9548 Background: Immunotherapies (ICI) and targeted therapies (TT) have improved PFS and OS in BRAF V600 -mutated advanced melanoma pts, but evidence regarding their optimal sequence is limited. The randomized phase 2 ImmunoCobiVem study evaluated efficacy and safety of an early switch to Atezo after initial treatment with V + C. Interim results are reported. Methods: Pts with previously untreated BRAF V600 -mutated advanced melanoma received a 3-mo run-in with V (960 mg twice daily) + C (60 mg once daily for 21/28 days). Pts without PD/treatment interruption due to AEs during run-in were then randomized 1:1 to continue V + C (Arm A) or switch to Atezo (1200 mg every 3 wks; Arm B) until first documented PD (PD1), followed by crossover to the alternate treatment until second documented PD (PD2). End points were PFS1 (time from start of run-in until PD1 or death from any cause), PFS2 (time from start of run-in until PD2 or death from any cause), PFS3 (time from PD1 until PD2 or death from any cause), DCR, ORR, OS, and safety. Results: 185 pts were enrolled between Nov 2016 and Dec 2019 (63% male; median age 58 y); 135 pts completed run-in and were randomized to Arm A (n=69) or Arm B (n=66). At data cutoff, median follow-up for all pts was 19.0 mo. In Arm A, 36/69 pts (52%) discontinued V + C due to PD and 21/36 (58%) crossed over to Atezo; in Arm B, 49/66 pts (74%) discontinued Atezo due to PD and 35/49 (71%) crossed over to V + C. Median PFS1 was significantly longer in Arm A vs Arm B (HR 0.55; 95% CI 0.37–0.84; P=0.001), while median PFS3 was significantly shorter in Arm A vs Arm B (HR 2.24; 95% CI 1.17–4.30; P=0.013); median PFS2 was not significantly different between arms (HR 1.57; 95% CI 0.83–2.96; P=0.163) (Table). During the randomized phase, ORR and DCR were higher in Arm A before crossover and in Arm B after crossover (Table). OS was similar between arms (HR 1.22; 95% CI 0.69–2.16; P=0.389). Median (range) treatment duration across treatment phases was 11.2 mo (2.3–56.1) for Arm A and 10.7 mo (2.8–56.7) for Arm B. Grade 3/4 AEs occurred in 55% of pts in Arm A and 64% in Arm B; AEs led to discontinuation in 10% and 12%, respectively. Conclusions: Early switch from V + C to Atezo is feasible and safe, but tumor control achieved in run-in is maintained in only a subset of pts on subsequent ICI monotherapy. Crossover to ICI monotherapy at PD results in low response, while response to TT re-exposure is frequent. Clinical trial information: NCT02902029. [Table: see text]
Materialart:
Online-Ressource
ISSN:
0732-183X
,
1527-7755
DOI:
10.1200/JCO.2022.40.16_suppl.9548
Sprache:
Englisch
Verlag:
American Society of Clinical Oncology (ASCO)
Publikationsdatum:
2022
ZDB Id:
2005181-5
