An open label randomized non-inferiority trial comparing adjuvant platinum plus paclitaxel to platinum plus 5-FU after curative resection in high-risk penile carcinoma.

Abstract

LBA5012 Background: There is limited evidence to guide adjuvant therapy in high-risk penile cancer. Methods: Patients with high-risk penile cancer [> 1 inguinal lymph node (LN), perinodal extension, pelvic LN, or LN > 4 cm] who underwent curative resection were randomized 1:1 to receive 4 cycles of platinum plus 5-FU (PF arm) or platinum plus paclitaxel (PP arm), followed by concurrent chemoradiotherapy. Primary endpoint was progression-free survival (PFS); secondary endpoints were overall survival (OS), toxicities and quality of life (QoL). The study was approved by IEC and registered with CTRI. Recruitment began in March 2017 but closed prematurely due to slow accrual. Results: Between March 2017 and October 2024, 49 patients were randomized (Table 1). Median follow-up was 60.1 months. There was no significant difference in median PFS (12.5 vs 35.9 months, p=0.460), 5-year PFS (36.1% vs 38.5%), median OS (21.6 vs 37.2 months, p=0.530) and 5-year OS (45.3% vs 41.1%) between PF and PP arm, respectively. Dose reductions were higher (33.3% vs 4.5%, p=0.015), similar dose delays (33.3% vs 31.8%, p=0.916) and a non-significant increase in drug discontinuation (42.9% vs 18.2%, p=0.078) in the PF arm. Grade 3/4 hematological (28.6% vs 4.5%, p=0.033) and gastrointestinal (33.3% vs 4.5%, p=0.015) toxicities were higher in PF arm. Infections (9.5% vs 13.6%, p=0.674) and hospitalizations (38.1% vs 18.2%, p=0.146) were similar. QoL (EORTC QLQ-C30 and MSHQ) analysis showed no difference in global health status (p=0.094), functional and symptom scales. Patients in PF arm reported more erectile dysfunction-related bother (p=0.018) while other MSHQ domains were similar. Conclusion: Adjuvant platinum plus 5-FU showed similar efficacy to platinum plus paclitaxel in high-risk penile carcinoma after curative resection, albeit with higher hematological and gastrointestinal toxicities, as well as erectile dysfunction-related bother. Clinical trial information: CTRI/2016/12/007567 . Baseline and treatment details. Characteristics 5-FU + Platinum(N = 25) Paclitaxel + Platinum(N = 24) p-value Age (years)  Median (Range) 49 (29-70) 51 (26-70) Co-morbidities  Hypertension 5 (20%) 5 (20.8%) 0.942  Diabetes Mellitus 5 (20%) 4 (16.7%) 0.763  Coronary Artery Disease 3 (12%) 1 (4.2%) 0.317  Prior phimosis 3 (12%) 1 (4.2%) 0.317  Smoker or smokeless tobacco 9 (36%) 10 (41.7%) 0.773 ECOG PS 0.715  0 2 (8%) 1 (4.2%)  1 21 (84%) 22 (91.6%)  2 2 (8%) 1 (4.2%) Surgery 0.995  Glansectomy 4 (16%) 4 (16.7%)  Partial penectomy 17 (68%) 16 (66.6%)  Total penectomy 4 (16%) 4 (16.7%) Degree of differentiation 0.566  Grade 1 2 (8%) 2 (8.3%)  Grade 2 12 (48%) 8 (33.3%)  Grade 3 11 (44%) 14 (58.3%) Pathological T stage 0.525  T1 10 (40%) 6 (25%)  T2 8 (32%) 9 (37.5%)  T3 7 (28%) 9 (37.5%) Pathological N stage 0.950  N2 4 (16%) 4 (16.7%)  N3 21 (84%) 20 (8.3%) LVI or PNI 11 (44%) 9 (37.5%) 0.644 > 3 adjuvant cycles 15 (60%) 22 (91.6%) 0.010 Completed CTRT 12 (48%) 14 (58.3%) 0.469