Pyoderma vegetans (PV) is an inflammatory dermatosis, characterized clinically by large exudative vegetating plaques, and histopathologically by epidermal pseudoepitheliomatous hyperplasia and dense inflammatory infiltrates. Although PV is a very rare condition, it is a chronic disorder that may accompany any systemic process that compromises immunity. Treatment is very difficult, and correction of predisposing causes may be useful. We present a 49-year-old woman affected by severe psoriatic arthritis since she was 19, with giant verrucous plaques on her lower limbs that had worsened progressively during the last 15 years. After ruling out other vegetating cutaneous disorders, PV was diagnosed in association with psoriasis. Despite numerous previous systemic and topical therapeutic attempts no response was observed. Etanercept was introduced, which resulted in a marked improvement within 3 weeks. Herein, we report a diagnostic and therapeutic challenge of the first case of PV associated with psoriasis that presented a good response to etanercept.
1075 Background: NGS in ctDNA from MBC is feasible and results may be informative for patients’ management, especially in non-luminal tumors (Oliveira et al, ASCO 2018). We aimed to study the determinants of concordance in CRG in a cohort of 60 MBC patients undergoing tBx and ctDNA collection. Methods: MiSeq Amplicon-based NGS (59 cancer-related genes) was performed in one single metastatic lesion per patient and compared with liquid biopsies taken at the same time point at disease progression to prior treatment. The concordance in CRG ( PIK3CA, AKT1, ERBB2, ESR1, PTEN, BRAF, FGFR1, HRAS, KRAS, and PIK3R1) in tBx vs ctDNA was determined at patient and at mutation (mut) level and correlated with mutant allele fraction (MAF), total disease volume (TDV), and clinical characteristics. True positive in plasma (TPP): patient with a mut detected both in ctDNA and tBx. TDV was defined as all metastasis volume assessed by CT scan (excluding sclerotic bone metastasis), and analyzed by an experienced radiologist using the 3DSlicer semiautomatic segmentation tool (TDV = pixel size x number of pixels). Results: Concordance in CRG at patient and mut level was 72% and 55%, respectively. Concordance for ERBB2 (1/1; 100%) and PIK3CA (17/22; 77%) was higher than for ESR1 (8/20; 40%) and AKT1 (2/6; 33%). ctDNA failed to detect 14 mut present in tBx ( ESR1 n = 5, PIK3CA n = 5, AKT1 n = 3, BRAF n = 1). Concordance was 100% for non-luminal and 60% for luminal cases (P = 0.01). In univariate analysis, concordance was not associated with MAF in tBx (P = 0.15), TDV (p = 0.86), number of prior lines of therapy (P = 0.57), number of metastatic sites (P = 0.56) or presence of visceral metastasis (P = 1.0). In patients with PIK3CA mut (N = 22), those with TPP had a numerically higher TDV than those where a PIK3CA mut was not detected in ctDNA (20.9cm3 vs 5.1cm3, P = 0.28). Across all patients, in the multivariate logistic model adjusted for other factors, TDV was a determinant of TPP (OR 1.02, 95%CI 1.0-1.06; P = 0.059). For each increase of 1cm3 in TDV, there was a 2% increase in the probability of detecting a mut in ctDNA. Conclusions: Our results suggest that liquid biopsy testing for the detection of actionable CRG is clinically valid in MBC, although its yield depends on several factors – tumor subtype, analyzed gene, and possibly tumor volume – that reflect both tumor heterogeneity and tumor shedding rate. Due to the potential clinical implications, the observation that mutation detection in ctDNA may correlate with tumor volume merits further study in a larger dataset.
Background: New strategies as immune blockade inhibitors and oncolytic viruses are opening new possibilities in cancer therapy. Preliminary results in melanoma showed that the combination of Talimogene Laherparevec (T-VEC) with an anti PD-L1 or anti CTLA4 has greater efficacy than either therapy alone, without additional safety concerns beyond those expected for each individual agent. The presence of residual cancer after neoadjuvant chemotherapy (NAC) in early breast cancer (BC) patients is an unmet medical need. We hypothesize that combining T-VEC with Atezolizumab may offer clinical benefit in the preoperative setting for early BC patients with intermediate to high risk of recurrence who present residual disease (RD) after standard NAC. Methods: PROMETEO is an open-label, multicenter trial of T-VEC in combination with Atezolizumab in patients with residual disease after completing standard NAC. 30 patients with triple negative breast cancer (TNBC) or Luminal B-like/Her2- (ER/PR>10% and Ki-67 ≥30% or ER/PR 1-10% and Ki-67 ≥20%) will be included. RD must be confirmed by core-biopsy and have a diameter ≥ 15mm measured by magnetic resonance imaging. Adequate organ function and ECOG PS 0-1 are required. T-VEC is administered intratumorally in week 1 (106 plaque-forming units/mL [pfu/mL]), then in week 4 and every 2 weeks thereafter (108 pfu/mL) for four injections. Atezolizumab (840 mg) is administered intravenously every 2 weeks for four infusions, beginning in week 4. BC surgery will be carried out 1 to 3 weeks after completion of study treatment. Primary objective is to evaluate the effect of T-VEC + Atezolizumab by comparing the expression of a gene signature tracking activated CD8 T-cells between RD at surgery and RD after NAC. We expect a relative increase of ≥20% in the expression of this CD8 T-cell gene signature in 20% of patients or more, defined as the mean expression of PRF1, CD8A, GZMM, CD8B and FLT3LG, between post and pre-treatment samples. Secondary endpoints include pathologic complete response rate and residual cancer burden, objective response rate, and safety. Two safety data reviews - after 4 and 10 patients complete treatment - are planned. A total of 4 sites in Spain are participating in the trial. To date, 4 patients have been included and it is expected to complete the first safety data review in September 2019. The study recruitment is planned to be completed by October 2020. Clinical trial identification: NCT03802604 Citation Format: Tomás Pascual, Patricia Villagrasa, María J Vidal, Sergi Ganau, Begoña Bermejo, Ana Julve, Esther Zamora, Ignacio Miranda, Estela Vega, Cristina Marquez, Mafalda Oliveira, Juan Miguel Cejalvo, Luis de la Cruz, Manel Juan, Jordi Canes, Xavier Gonzalez, Aleix Prat. SOLTI-1503 PROMETEO: Combination of talimogene laherparepvec (T-VEC) with atezolizumab in patients with residual breast cancer after standard neoadjuvant multi-agent chemotherapy [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr OT1-01-01.
Background Residual disease (RD) following neoadjuvant chemotherapy (NAC) in early HER2 negative breast cancer (BC) remains an unmet medical need. We hypothesized that combining T-VEC with Atezolizumab may offer clinical benefit in terms of residual cancer burden (RCB) rate in the pre-operative setting for patients with early BC with intermediate to high risk of recurrence who present RD after standard NAC. Methods SOLTI-1503 PROMETEO is an open-label, multicenter trial of T-VEC + Atezolizumab in patients with RD after completing standard NAC. Overall, 30 women with triple-negative BC (TNBC) or Luminal B-like/HER2-negative BC are planned to be included in the trial. RD must be confirmed by core-biopsy and tumor should have a diameter ≥ 10 mm measured by magnetic resonance imaging (MRI). Adequate organ function and ECOG PS 0-1 are required. T-VEC is administered intratumorally on week 1 (106 plaque-forming units/mL [pfu/mL]), then in week 4 and every 2 weeks thereafter (108 pfu/mL) for 4 injections. Atezolizumab (840 mg) is administered intravenously every 2 weeks for 4 infusions, starting at week 4. BC surgery is performed 1 to 3 weeks after completing the treatment. The primary objective is to evaluate the efficacy of the combination, measured by the rate of RCB class 0/1 at surgery. Secondary endpoints include rate of pCR, objective response rate (ORR; rate of complete response + partial response) assessed by MRI, safety, and the increase of mean expression of a gene signature tracking activated CD8+ T-cells. Here we present the safety and efficacy results of the interim analysis including the first 10 enrolled patients. Results: As of April 2021, 10 patients received the study treatment and were evaluable for primary endpoint and safety. Main patient characteristics were: median age 48 (37-71), ECOG PS 0 (70%) and post-menopausal (60%). Four patients had TNBC and 6 Luminal B-like BC; 5 patients had stage II BC and 4 stage III; 7 tumors were grade II and 3 were grade III; median Ki-67 was 44% (20-75). Mean tumor size by MRI after NAC was 30.5 mm (11-75). At surgery, one patient achieved RCB0. Two patients achieved an objective response, five patients a stable disease and disease progression was observed in three patients (2 TNBC and 1 Luminal-like tumor). Nine patients reported AEs. Only grade 1-2 adverse events were reported, being the most common Fever (n=6) Arthralgia ((n=4) AST increased (n=3) and ALT increased (n=3). Conclusion: The treatment of T-VEC and atezolizumab was feasible at the approved doses and the safety profile was consistent with that previously reported. One patient achieved RCB0. After the efficacy and safety analysis of the first 10 patients, it was decided to continue with the inclusion of up to 30 patients. Correlative analysis including gene expression analysis and centralized Tumor-infiltrating lymphocytes (TILs), PD-L1 (SP142) IHC will be presented. Citation Format: Tomás Pascual, Maria Vidal, Mafalda Oliveira, Juan M Cejalvo, Estela Vega, Esther Sanfeliu, Sergi Ganau, Ana Julve, Esther Zamora, Ignacio Miranda, Ana Delgado, Begoña Bermejo, Luis de la Cruz, Claudette Falato, Manel Juan, Juan M Ferrero-Cafiero, Xavier González-Farré, Patricia Villagrasa, Aleix Prat. Talimogene laherparepvec (T-VEC) + atezolizumab combination in early breast cancer (SOLTI-1503 PROMETEO): Safety and efficacy interim analysis [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P2-14-13.
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