SP1049C has a notable single-agent activity in patients with adenocarcinoma of the esophagus and GEJ, as well as an acceptable safety profile. These results, in addition to the results of preclinical studies demonstrating superior antitumor activity of SP1049C compared with doxorubicin in a standard formulation, indicate that further evaluations of SP1049C alone or combined with other relevant therapeutics in this disease setting are warranted.

4080 Background: SP1049C (a block co-polymer incorporating doxorubicin) has demonstrated broad in vitro activity and superior anti-tumour activity in 9/9 in vivo animal tumour models compared to doxorubicin. Methods: Chemotherapy- or radiotherapy-naïve patients with measurable, inoperable, recurrent or metastatic adenocarcinoma of the oesophagus; KP ≥60; normal cardiac LVEF; adequate swallowing and adequate renal, hepatic and bone marrow function were eligible. SP1049C 75mg/m2 IV 30-minute infusion was given q3w, for up to 6 cycles. Radiological response was assessed after cycles 2, 4 and 6. Upon disease progression (PD) patients were offered standard chemotherapy. QoL (by QLQ-C30 and QLQ-OES24 questionnaires), toxicity, disease-related symptoms and cardiac function were also prospectively assessed. Results: From February 2002 to December 2004, 21 patients (all male), median age 62 years (range 38–78) with stage 3 (n = 1) of stage IV (n = 20) disease were enrolled. Response rate (WHO criteria) in 19 patients eligible for efficacy analysis (radiologically re-assessed after ≥2 cycles of treatment) included: PR 9/19 (47%), SD (8/19) 42% and PD (2/19) 11% by investigator assessment (confirmed PR 41%, unconfirmed PR 12% and SD 29% by independent review, RECIST criteria). One responding patient underwent salvage resection of a pT2N0 (Stage 2A) tumour. All patients are evaluable for toxicity. Toxicity (Gd 1–2/3–4, by patient) included: neutropaenia 24%/62%, leucopaenia 19%/29%, anaemia 38%/5% and thrombocytopaenia 9.5%/0% (resulting in 9 (43%) patients being dose-reduced to 55 mg/m2 at cycle 2), nausea 81%/19%, vomiting 62%/24%, anorexia 52.4%/14%, lethargy 81%/14%, febrile neutropaenia -/29%, mucositis 48%/5%, and Gd 1–2 alopecia in 67%. Grade I cardiotoxicity (fall in LVEF by 10–19% from baseline, CTC v2.0) was seen in 4 (19%) patients. The median overall survival (all patients) is 10 months; four patients received 2nd-line chemotherapy. Conclusions: SP1049C appears to have activity in monotherapy in this patient group and combination studies with other active agents are warranted. [Table: see text]

5016 Background: ADT with salvage RT improves survival for men with PSA recurrence after RP. For high risk PSA recurrence, current standard ADT duration is up to 2 years with RT; shortening but intensifying systemic therapy may improve outcomes. The STREAM trial showed 6 mo enzalutamide with ADT/RT had 3-year progression free survival (PFS) of 53% in a high risk population, including lymph node (LN) positive. Given docetaxel (doce) improves survival in mHSPC, we evaluated the combination of salvage RT, ADT/apalutamide (apa) and doce in this setting. Methods: STARTAR is a multicenter investigator initiated phase 2 trial for salvage treatment of PSA recurrent PC post-RP, conducted in the DOD Prostate Cancer Clinical Trials Consortium. Key inclusion criteria included Gleason 7 with T3/positive margin/N1 or Gleason 8-10 PC, PSA relapse <4 years post-RP (inclusion PSA 0.2-4 ng/mL), and <4 positive LNs, standard imaging negative. Patients (pts) received ADT with apa for 9 months, RT (66-74 Gy to the prostate bed +/- pelvic LNs over 6-8 wks) starting wk 8, and then completed 6 cycles of concurrent doce 75mg/m2 q3 wks. The primary endpoint was 36 month PFS, defined as composite of freedom from PSA>0.2 + post-RT nadir with subsequent rise, clinical progression, other therapy start, or death, among pts with testosterone (T) recovery (>100ng/dL). Kaplan-Meier estimates for PFS were used to determine landmark 24 mo and 36 mo rates and compared to PFS rates from prior trials using a binomial test. Results: From 3/2018 to 2/2020, 39 pts were enrolled. As of 12/2022 data cutoff, median follow up was 36 months. Baseline characteristics: Gleason 7 in 54%; Gleason 8-10 in 46%; 23% LN positive; median PSA 0.58 ng/mL (range 0.21-3.40), and median time from RP 7.6 mo (range 2-98). 37 pts (95%) and 23 pts (62%) completed at least 1 and all 6 cycles doce, respectively. All pts achieved undetectable PSA nadirs. At 24mo and 36mo, PFS rates were 84% and 72%, respectively, with 95% pts recovering T at 36 mo. Compared to 40% historical PFS and 53% STREAM PFS rates, the 72% 36-mo PFS rate was statistically significantly improved (p<0.001 and p=0.013, respectively). Common any-grade adverse events (AEs) included 98% hot flashes, 88% fatigue, 77% alopecia, 57% dysgeusia, and 53% rash (28% grade 1; 15% grade 2, 10% grade 3), with 5% febrile neutropenia. Conclusions: In this first phase 2 trial of ADT, apa, salvage RT, and 6 cycles of doce for high risk PSA recurrence, the primary endpoint 3-year PFS rate improved to 72%, indicating durable remissions beyond historic controls. Intensifying systemic treatments in the non-metastatic hormone sensitive but high risk salvage setting may be feasible and efficacious, with fewer pts experiencing cancer progression over time. Clinical trial information: NCT03311555 .

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