Neoadjuvant anti-programmed cell death 1 therapy for locally advanced basal cell carcinoma in treatment-naive patients: A case series.
Ontology highlight
ABSTRACT:
SUBMITTER: Ligtenberg KG
PROVIDER: S-EPMC7317689 | biostudies-literature | 2020 Jul
REPOSITORIES: biostudies-literature
Publications
Neoadjuvant anti-programmed cell death 1 therapy for locally advanced basal cell carcinoma in treatment-naive patients: A case series.
Ligtenberg Katherine Given KG Hu Jamie Katy JK Damsky William W Olino Kelly K Kluger Harriet H Clune James J Cowper Shawn E SE Panse Gauri G Leventhal Jonathan J Weiss Sarah A SA
JAAD case reports 20200517 7
Similar Datasets
Project description:BackgroundImmunotherapy is effective in treating unresectable esophageal squamous cell carcinoma (ESCC), but little is known about its role in the preoperative setting. The aim of this study was to evaluate the safety, feasibility and efficacy of neoadjuvant treatment with camrelizumab plus chemotherapy in locally advanced ESCC.MethodsPatients diagnosed with locally advanced ESCC were retrospectively included if they had received neoadjuvant camrelizumab plus nab-paclitaxel and S1 capsule followed by radical esophagectomy between November, 2019 and June, 2020 at Sun Yat-sen University Cancer Center. Primary endpoints were safety and feasibility. In addition, pathological response and the relationship between tumor immune microenvironment (TIME)/tumor mutational burden (TMB) and treatment response were also investigated.ResultsTwelve patients were included and they all received three courses of preoperative treatment with camrelizumab plus nab-paclitaxel/S1. No grade 3 or higher toxicities occurred. No surgical delay or perioperative death was reported. Nine patients (75%) responded to the treatment, four with a complete pathological response (pCR) and five with a major pathological response (MPR). Neither programmed death-ligand 1 (PD-L1) expression nor TMB was correlated with treatment response. TIME analysis revealed that a higher abundance of CD56dim natural killer cells was associated with better pathological response in the primary tumor, while lower density of M2-tumor-associated macrophages was associated with better pathological response in the lymph nodes (LNs).ConclusionsNeoadjuvant camrelizumab plus nab-paclitaxel and S1 is safe, feasible and effective in locally advanced ESCC and is worth further investigation.
| S-EPMC8421958 | biostudies-literature
Project description:BackgroundInhibition of the programmed cell death-1/programmed cell death-ligand 1 (PD-1/PD-L1) axis in combination with radiotherapy may be a promising approach to treat cancer. In the present study, we aimed to evaluate serum soluble PD-1/PD-L1 levels in patients with advanced rectal cancer treated with neoadjuvant chemoradiotherapy (CRT).MethodsSerum soluble PD-L1 and PD-1 levels were measured using an enzyme-linked immunosorbent assay before and after CRT in 117 patients with low rectal cancer. Changes in the levels of sPD-L1/PD-1 after CRT, and the correlation between sPD-L1/PD-1 level and clinicopathological characteristics or disease-free survival (DFS) were evaluated.ResultssPD-L1 levels significantly increased after CRT (p < 0.0001), whereas sPD-1 levels did not change significantly (p = 0.1050). High sPD-L1 before CRT was significantly associated with younger age (p = 0.044), and after CRT, with lymphovascular invasion (p = 0.021). High sPD-1 before and after CRT was significantly associated with a longer distance of the tumor from the anal verge (both p < 0.001). There was no correlation between sPD-L1 level and local PD-L1 expression on stromal immune cells. High sPD-L1 level after CRT tended to be associated with worse DFS (p = 0.0752). The multivariate analysis could not demonstrate an independent association for sPD-L1 levels after CRT with DFS.ConclusionsSignificant increase of sPD-L1 levels after CRT suggests that anti-PD-L1 therapy might be a potential treatment strategy in combination with CRT in advanced rectal cancer.
| S-EPMC6390997 | biostudies-literature
Project description:BackgroundSurgery is the primary treatment for basal cell carcinoma (BCC). In locally advanced basal cell carcinoma (laBCC), surgery may cause functional or aesthetic damage. In laBCC, neoadjuvant administration of vismodegib, an inhibitor of the Hedgehog signaling pathway, may reduce tumor size, facilitate resection, and reduce functional and aesthetic consequences of surgery. The VISMONEO study assessed efficacy and safety of vismodegib in neoadjuvant treatment of laBCC.MethodsVISMONEO (NCT02667574) is an open-label, noncomparative, multicenter, phase 2 study. Patients with ≥1 histologically confirmed facial BCC, inoperable or operable with functional or major aesthetic sequelae risk, were included. Oral vismodegib 150 mg was administered once daily for 4 to 10 months before planned surgery, which was performed once the best response under vismodegib was observed. Primary endpoint was percentage of patients with BCC with tumor downstaging following surgical resection after neoadjuvant vismodegib. Downstaging was defined according to a 6-stage surgical classification related to the aesthetic and functional consequences of surgery.Findings55 patients (median age: 73 years) with laBCC were included from November 2014 to June 2015. At inclusion, 4 patients were inoperable, 15 were operable with a major functional risk, and 36 were operable with a minor functional risk or a major aesthetic risk. Mean size of target lesion was 47.3 mm (SD: 27.2 mm). 44 patients presented with downstaging after vismodegib treatment (80%; 95% confidence interval [CI], 67 to 90). Of these 44 patients, 27 had a complete response (25 proved by biopsy). Mean treatment duration was 6.0 months. Overall Response Rate according to RECIST 1.1 criteria was 71% (95% CI, 59 to 88). At 3-years of follow-up, 16/44 patients had known recurrence (36%; 95%CI, 22 to 51).InterpretationNeoadjuvant vismodegib allows for a downstaging of the surgical procedure for laBCCs in functionally sensitive locations.FundingVISMONEO was funded by F. Hoffmann-La Roche Ltd.
| S-EPMC8093898 | biostudies-literature
Project description:IntroductionBasal cell carcinoma (BCC) is treated with local surgery or noninvasive treatment modalities. If a BCC remains untreated, it can develop into a locally advanced BCC or a metastatic BCC.Case presentationHere we report in detail the management of three complex advanced BCC (aBCC) after treatment failure with vismodegib. On all tumors, next generation DNA sequencing in the Center for Personalized Cancer Treatment-02 (CPCT-02) study was performed; subsequently, patients were included in the Drug Rediscovery Protocol (DRUP) trial, in which treatment was started with commercially available targeted anticancer drugs based on the molecular tumor profile. All patients showed partial response or stable disease following treatment with second line PD-1 inhibitors with an average duration of response of 12.3 months.Discussion/conclusionImmunotherapy can be a treatment option for aBCC resistant to hedgehog pathway inhibitor treatment. However, despite the high tumor mutational burden of aBCCs, immunotherapy does not always lead to a long response. Rechallenge or combining treatment of hedgehog inhibitors and PD-1 inhibitors by parallel or alternating cycles may be a strategy to lengthen the treatment response.
| S-EPMC11250645 | biostudies-literature
Project description:BackgroundWe assessed the surrogacy of objective response rate (ORR), disease control rate (DCR) and progression-free survival (PFS) for overall survival (OS) in anti-PD-1/PD-L1 trials of metastatic melanoma through a meta-analysis of randomized controlled trials (RCTs).MethodsPubMed and EMBASE were searched for phase II/III RCTs till June 2019 investigating anti-PD-1/PD-L1 agents. Treatment effect (hazard ratio or odds ratio) on potential surrogates (ORR/DCR/PFS) and OS were collected. At trial level, we assessed the correlation between treatment effect on potential surrogates and OS, weighted by sample size, fixed and random effect models, and calculated the surrogate threshold effect (STE). Sensitivity analyses and leave-one-out cross-validation approach were performed to evaluate the robustness of our findings.ResultsWe included 8 RCTs (4110 patients; 11 comparisons). We did not identify strong correlations between ORR [coefficient of determination (R 2): 0.09-0.25], DCR (0.41-0.57) and OS. However, we noted a strong correlation between PFS and OS, with R 2 of 0.82 in sample size, 0.75 in fixed effect and 0.72 in random effect model weighting, the robustness of which was further verified by leave-one-out cross-validation approach. Sensitivity analyses with restriction to trials with less than 50% crossover, phase III trials, large trials and first-line trials strengthened the correlation (0.78-0.94). The STE for PFS was 0.78.ConclusionsPFS may be the appropriate surrogate for OS in anti-PD-1/PD-L1 trials of metastatic melanoma. A future anti-PD-1/PD-L1 trial would need less than 0.78 for PFS of the upper limit of confidence interval to predict an OS benefit.
| S-EPMC7301660 | biostudies-literature
Project description:BackgroundIn recent years, neoadjuvant immunotherapy with chemotherapy has shown increasing promise for locally advanced non-small cell lung cancer (NSCLC). However, to establish its clinical efficacy and safety, it is imperative to amass more real-world clinical data. This retrospective study aims to assess the safety and effectiveness of combing sintilimab, a PD-1 inhibitor, with chemotherapy as a neoadjuvant treatment modality in patients diagnosed with potentially resectable NSCLC.MethodsWe retrospectively reviewed patients with stage II-III NSCLC receiving neoadjuvant chemoimmunotherapy in Sichuan Cancer Hospital between February 2021 and February 2023. Sintilimab injection (intravenously,200 mg, iv, d1, q3w) and platinum-based chemotherapy were administered intravenously every 3 weeks, with radical lung cancer resection planned approximately 4-11 weeks after the last dose. The primary endpoint of the study was pathologic complete response (pCR). The secondary endpoints were objective response rate (ORR), and safety.ResultThirteen patients were enrolled, they were mostly diagnosed with stage III NSCLC (IIB 15.4% IIIA 38.5%; IIIB 46.2%). Most of them had pathologically confirmed squamous cell carcinoma (69.2%). All patients received sintilimab combined with platinum-based chemotherapy for 2 to 4 cycles. Notably, none of the patients necessitated a reduction in initial dosages or treatment postponement due to intolerable adverse events. Then, all of them underwent surgical operation. Impressively, nine patients (69.2%) achieved a pathologic complete response. The objective response rate (ORR) stood at 46.15%. Nine patients experienced neoadjuvant treatment-related adverse events (TRAEs), with only one patient (7.6%) encountering a grade 4 neoadjuvant TRAE.ConclusionTherefore, the current study suggested that neoadjuvant sintilimab plus platinum-based chemotherapy can be a safe approach in increasing the efficiency of treatment and hopefully improving the prognosis of patients with potentially resectable locally advanced NSCLC.
| S-EPMC10521519 | biostudies-literature
Project description:BackgroundLocally advanced basal cell cancer is a rare and challenging clinical problem. Historically, these patients were treated with aggressive surgery or radiotherapy. Most sporadic basal cell carcinomas have somatic mutations in the hedgehog pathway. Oral hedgehog inhibitors induce rapid and often complete clinical responses in locally advanced basal cell tumors. Unfortunately, these responses are usually transient. We hypothesized that treatment failure represents persistence of drug resistant cells that could be eradicated by addition of localized radiotherapy.Materials and methodsWe performed a retrospective review of our patients with locally advanced basal cell cancer treated with sonidegib or vismodegib induction therapy who were treated with added superficial radiotherapy at the time of maximal response.ResultsTwelve patients met inclusion criteria. All patients achieved a complete response following hedgehog inhibitor therapy with addition of radiotherapy. Progression-free survival at 40 months was 89%, with a median follow-up of 40 months. Relapses occurred in only 2 of 12 patients (16.6%). Nine patients experienced grade I-II toxicity from hedgehog inhibitor induction therapy (taste changes [3], weight loss [3], muscle cramps [3]). Eight patients experienced mild radiotherapy-induced skin toxicity during concurrent therapy. No patients had to discontinue treatment.ConclusionInduction therapy with hedgehog inhibitors followed by addition of concurrent radiation therapy resulted in an extremely high clinical response rate with relatively minor and reversible toxicity. This gave a high rate of progression-free survival and a low disease-specific progression rate. Further prospective evaluation of this treatment approach is needed to confirm the apparent clinical activity.Implications for practiceLocally advanced basal cell cancers are challenging to treat. Previously, aggressive surgical resection or radiotherapy represented the best treatment options. Most basal cell cancers have somatic mutations in the hedgehog pathway. Oral inhibitors of this pathway produce rapid but transient clinical responses. This study reports 12 patients treated with hedgehog inhibitor induction therapy to near-maximal response. Addition of concurrent involved field radiotherapy resulted in a very high complete response rate with minimal toxicity. There was prolonged progression-free survival in 90% of patients. This study identified a novel treatment approach for patients with advanced basal cell carcinoma.
| S-EPMC8649029 | biostudies-literature
Project description:Basal cell carcinoma (BCC) is the most common cancer in Caucasians, and its incidence continues to rise. Generally, BCCs have good outcomes when diagnosed and treated early. However, 1-10% of patients will develop advanced disease due to either delays in accessing treatment or aggressive tumors that may be refractory to treatment. Locally advanced basal cell carcinomas (laBCCs) are large, aggressive, or recurrent tumors that have the potential to invade surrounding tissues including bone, cartilage, nerve, and muscle. Treatment requires a multi-disciplinary approach where different modalities including surgery, radiation therapy, Hedgehog Pathway Inhibitors, and immunotherapy can be considered.
| S-EPMC8765439 | biostudies-literature
Project description:IntroductionHepatocellular carcinoma (HCC) is one of the leading causes of cancer-related death worldwide. Today, a promising treatment strategy is focused on the enhancement of antitumor immune responses by immune checkpoint modification. However, as only 20% of patients with HCC are responders, identification of predictive factors is urgently required. Therefore, for the first time, the features of the intrahepatic and circulating immune system in patients with advanced-stage HCC, before and during the treatment, were analyzed.MethodsWe collected fresh HCC biopsies, along with adjacent tumor-free liver tissues and peripheral blood samples, from 21 patients with advanced HCC. Furthermore, we performed an extensive immunomonitoring of patients with HCC treated with sorafenib or programmed death (PD)-1/PD-L1 pathway blockade using multiparametric flow cytometry.ResultsWe observed that regardless of the treatment, low baseline intratumoral CD4/CD8 T-cell ratio was associated with better overall survival (P = 0.0002). The baseline frequency of intratumoral PD-1 CD8 T cells was significantly lower in patients responding to sorafenib treatment than in the nonresponders (P = 0.0117), and the frequency of circulating PD-1 T cells increased with tumor progression (P = 0.0329). By contrast, responders to PD-1/PD-L1 pathway blockade showed a trend of high baseline frequency of intratumoral PD-1 CD8 T cells. Moreover, we observed a trend of LAG3 and TIM3 upregulation on circulating T cells in nonresponding patients to PD-1/PD-L1 pathway blockade.DiscussionImmunosuppressive state, characterized by an enhanced intratumoral CD4/CD8 T-cell ratio, was associated with poor prognosis. Additionally, our results suggest that the frequency of intratumoral PD-1 CD8 T cells may serve as a biomarker to identify which individuals will benefit from which treatment and support the use of combination strategies.
| S-EPMC6708670 | biostudies-literature
Project description:Triple-negative breast cancer (TNBC) has the worst prognosis among all molecular types of breast cancer. Because of the strong immunogenicity of TNBC cells, programmed death 1/programmed death ligand 1 (PD-1/PD-L1) inhibitors, two kinds of immune checkpoint blockade agents, might help improve the prognosis of TNBC. However, how to better use PD-1/PD-L1 inhibitors and select patients who may benefit from treatment options remains controversial. This article summarizes published clinical studies in which PD-1/PD-L1 inhibitors were used in patients with advanced TNBC to explore how to maximize effectiveness of these medications.
| S-EPMC9086576 | biostudies-literature