Feldman, Darren Richard

5017 Background: HDCT/ASCT represents a curative salvage treatment for patients with GCT but is rarely used for other solid tumors. Patients undergoing HDCT/ASCT for hematologic neoplasms require revaccination for their childhood immunizations. Whether this is necessary in patients with GCT is unknown. Methods: In this prospective longitudinal study, patients with GCT undergoing HDCT-ASCT from 11/2010 to 5/2018 had serologies for Measles, Mumps, Rubella, Diphtheria, Tetanus, Polio, and Varicella Zoster measured before HDCT and at 3, 6, and in a subset, 12+ months after the last HDCT with results at these timepoints compared using descriptive statistics. In addition, titer levels at ≥6 months post-transplant were matched 1:1 for age and gender with HL patients who underwent HDCT/ASCT during the same time period. Immunity was compared between cohorts using the Cochran-Mantel-Haenszel test. Results: Of 80 patients with GCT (median age 30, 84% nonseminoma), 91% received 3 sequential transplants and 68 had repeat titers at ≥6 months. Immunity at baseline was >95% for Diphtheria, Tetanus and Polio and 89% for Varicella Zoster but lower for Measles (74%), Mumps (85%), and Rubella (83%) (Table). Compared to baseline, proportional immunity for all infections was similar at 3, 6, and 12 months post-transplant in the GCT population (≥6 months shown in Table). Matching resulted in 58 GCT-HL pairs. One-year immunity was numerically lower for most infections in the HL vs. GCT patients and significantly decreased for Measles and Rubella (Table). Conclusions: To our knowledge, this is the first study to assess vaccine titers following HDCT/ASCT for GCT. We demonstrate that HDCT/ASCT does not result in loss of immunity to childhood vaccines and that GCT patients retain protective titers more frequently than those with HL. However, 15-31% of GCT patients lack MMR immunity at baseline and at 1-year post-ASCT. Therefore, we recommend checking MMR titers at 1-year post-ASCT with revaccination of those lacking immunity. Titer evaluation and revaccination is not necessary for other childhood immunizations.[Table: see text]

Testicular cancer is relatively uncommon and accounts for <1% of all male tumors. However, it is the most common solid tumor in men between the ages of 20 and 34 years, and the global incidence has been steadily rising over the past several decades. Several risk factors for testicular cancer have been identified, including personal or family history of testicular cancer and cryptorchidism. Testicular germ cell tumors (GCTs) comprise 95% of malignant tumors arising in the testes and are categorized into 2 main histologic subtypes: seminoma and nonseminoma. Although nonseminoma is the more clinically aggressive tumor subtype, 5-year survival rates exceed 70% with current treatment options, even in patients with advanced or metastatic disease. Radical inguinal orchiectomy is the primary treatment for most patients with testicular GCTs. Postorchiectomy management is dictated by stage, histology, and risk classification; treatment options for nonseminoma include surveillance, systemic therapy, and nerve-sparing retroperitoneal lymph node dissection. Although rarely occurring, prognosis for patients with brain metastases remains poor, with >50% of patients dying within 1 year of diagnosis. This selection from the NCCN Guidelines for Testicular Cancer focuses on recommendations for the management of adult patients with nonseminomatous GCTs.

4563 Background: We previously reported no difference in favorable response rate (FRR) or PFS for TIP vs BEP. Here we present results of a pre-planned analysis of biomarkers of outcome. Methods: HCG and AFP were drawn on days 1 and 15 of each cycle and rates of decline classified as satisfactory [S] or unsatisfactory [US] by MSK (Motzer JCO 2007) and GETUG (Fizazi Lancet Oncol 2014) methods. IHC for ERCC1, RAD51, PARP1, HER-2, and p-AKT was performed on pre-treatment tumor samples. An H-score (0 – 300) was calculated for each stain (H = stain intensity [0 – 3] x % positive cells [0-100]). H-score and marker decline category were correlated with FRR (PR + CR) and PFS. Patients (pts) who received disease-stabilizing chemotherapy were excluded from marker analyses. Results: Of 91 pts, 80 did not receive disease-stabilizing treatment with 79 having sufficient marker values for analysis by the MSK method and 75 by GETUG. By MSK, 49 had S decline vs 30 US; by GETUG, 34 S vs 41 US. FRR and PFS were improved for pts with S vs US decline by both methods and remained significant by the MSK method when stratified by IGCCCG group (Table). IHC (n=77) quality was adequate in 71 to 73 pts (varied by stain) and was positive (H >0) for PARP in 68/73, ERCC1 in 54/71, RAD51 in 54/73, p-AKT in 5/72, and HER2 in 4/72. Only PARP1 was associated with outcome with worse PFS for the lowest expression tertile (H < 180; p=0.013). Conclusions: PARP1 expression and tumor marker decline rates, particularly by MSK method, were significantly associated with outcome to initial chemotherapy in int/poor risk GCT. Future trials incorporating marker decline into treatment allocation and validating the prognostic effect of PARP1 expression are warranted. Clinical trial information: NCT01873326. [Table: see text]

364 Background: Flavopiridol + FOLFOX showed activity in refractory GCT pts in a phase I trial (Rathkopf, Clin Cancer Res, 2009). This phase II study assessed the efficacy of this regimen in refractory GCT and the necessity of including 5-FU/LV. Methods: Previously treated pts with progressive GCT were eligible if they had received or were not candidates for high-dose chemotherapy (HDCT). Pts on Arm A received flavopiridol 70mg/m2 plus oxaliplatin 85mg/m2. Arm B (flavopiridol + FOLFOX) tested identical doses of flavopiridol and oxaliplatin plus 5-FU (400mg/m2 bolus, then 1800mg/m2 over 48 hours) and LV 400mg/m2. Treatment was every 2 weeks in 6-week cycles. The primary endpoint was response rate (RR) by RECIST. An identical Simon 2-stage design was used for each arm to differentiate between a RR ≥40% vs. ≤20%, with arm B opening only if arm A was ineffective. With ≥3 responses among the first 12 pts, another 13 pts would be enrolled with responses in ≥8/25 pts needed to show efficacy. Tumor biopsies pre-, during, and post-treatment were assessed by IHC for p53, p21, and cleaved caspase-3. Results: Of 36 pts (7 arm A, 29 arm B), 33 had nonseminoma. Primary site was testis in 27 and mediastinum in 7; 22 pts had received prior HDCT and 13 had LR (>2 years), including 2 on arm A and 11 on arm B. Arm A closed early after 0/7 pts responded (2 SD). Of 25 evaluable pts on arm B, 6 achieved a PR, 9 had SD, and 10 had PD. Notably, 5/10 evaluable LR pts on Arm B had a PR, including 1 pathologic CR, 1 PR-negative markers who received radiation (RT) to a residual bone metastasis, and 1 PR-positive markers who received RT to a residual nodal mass. These 3 pts remain disease-free ≥19 months (m) post-chemotherapy and ≥17m post-RT or surgery. Median PFS and OS were 2.3m and 7.3m for all pts and 3.2m and 11.2m for arm B pts. There was 1 treatment-related death due to sepsis. Conclusions: Although neither arm met the prespecified endpoint, flavopiridol plus FOLFOX (arm B) was particularly active in LR pts, with a 50% overall RR, including several durable responses. Further study of FOLFOX with or without flavopiridol is warranted in LR pts. Correlative data will be presented. Clinical trial information: NCT00957905.