In:
Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 41, No. 6_suppl ( 2023-02-20), p. 511-511
Abstract:
511 Background: Perioperative platinum-based chemo for UTUC improves pathologic responses and disease-free survival (DFS) while anti-PD1 monotherapy has limited activity to date (PURE-02). Here, we report the results from stage 1 of a phase II neoadjuvant trial of N+I for cisplatin-ineligible patients (pts) with UTUC. Methods: Cisplatin-ineligible pts with histologically confirmed high-grade UTUC and/or radiographically invasive UTUC with positive selective urine cytology were eligible. Pts were treated with I 3mg/kg + N 1mg/kg (weeks [wk] 0, 6), and N 3mg/kg (wk 3) prior to radical nephroureterectomy (NU). The primary endpoint (EP) was pathologic complete response (pCR, ypT0pN0) and secondary EPs included 〈 ypT2pN0 rate, DFS, and toxicity. The study has a Simon optimal two-stage design: if ≥1/9 pts achieved pCR in stage 1, the trial would proceed to accrue 24 total pts. Next generation sequencing of pre-treatment tumors was correlated with pathologic response. Results: Nine pts were enrolled between 2/2021-7/2022 with median age 71 (range 62-86), 89% male. Primary sites included ureter, n=6; renal pelvis, n=2; and both, n=1. Four pts (44%) had hydronephrosis. Median tumor diameter was 3.0 cm, (range: not measurable to 4.2 cm). Six pts (67%) received all planned treatment; N+/-I was stopped early for CTCAE grade 2 hyperthryoidism, n = 1; grade 2 diarrhea, n = 1; and grade 3 pneumonitis, n = 1. Median time from last treatment to NU was 1.7 months (range 0.6-3.7). No progression was noted on systemic therapy and all pts underwent NU, with pCR in 3/9 pts (33%) and 〈 ypT2pN0 in 6/9 (67%). Two pts had metastatic recurrence at 10.3 and 15.6 months after treatment initiation, while 1 pt died of post-op complications related to bowel leak 7.2 months after N+I initiation (4.7 months after NU) and 1 died 9.2 months after N+I initiation (4.7 months after NU) from complications of a fall unrelated to disease, surgery or N+I. Median tumor mutational burden (TMB) in 7 pts with pre-treatment sequencing was 13.2 mutations/megabase (range 6.6-106.3); all 3 pts with TMB 〈 10 were 〉 ypT1 or node positive at NU and all 4 pts with TMB 〉 10 were 〈 ypT1pN0. Three pts (43%) had FGFR3 driver mutations. Three pts had confirmed pathogenic germline variants in mismatch repair genes (MSH2, n=2; MLH1, n=1), all of which achieved pCR (n=1) or ypTaN0 (n=2) and remained alive and disease-free at last follow-up. CTCAE grade ≥3 treatment-related adverse events occurred in 4 pts (1 myasthenia, 1 maculopapular rash, 1 pneumonitis, 1 hepatitis plus elevated lipase). Conclusions: In this cohort of cisplatin-ineligible pts with UTUC, neoadjuvant N+I showed clinical activity meeting the trial’s Simon optimal two-stage design’s criteria to proceed to the second stage. All pts with pathogenic germline variants in mismatch repair genes achieved 〈 ypT1pN0 and remain free of disease. Clinical trial information: NCT03520491 Clinical trial information: NCT03520491 .
Type of Medium:
Online Resource
ISSN:
0732-183X
,
1527-7755
DOI:
10.1200/JCO.2023.41.6_suppl.511
Language:
English
Publisher:
American Society of Clinical Oncology (ASCO)
Publication Date:
2023
detail.hit.zdb_id:
2005181-5
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