Personalized response-driven adjuvant therapy after combination ipilimumab and nivolumab in high-risk resectable stage III melanoma: PRADO trial.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. TPS9605-TPS9605 ◽  
Author(s):  
Irene Reijers ◽  
Elisa A. Rozeman ◽  
Alexander M. Menzies ◽  
Bart A. Van De Wiel ◽  
Hanna Eriksson ◽  
...  
Keyword(s):  
Lymph Node ◽  
Stage Iv ◽  
Pathologic Response ◽  
Pathological Response ◽  
Stage Iii ◽  
Phase 2 ◽  
Primary Endpoints ◽  
Phase 1B ◽  
Stage Iii Melanoma

TPS9605 Background: Adjuvant (adj) immune checkpoint inhibition (ICI) improves relapse free survival (RFS) in stage III melanoma patients (pts). However, preclinical and translational data suggest that neo-adjuvant (neoadj) treatment might be favorable due to broader immune activation. The phase 1b OpACIN study comparing neoadj to adj IPI plus NIVO demonstrated a high pathological response rate (pRR) of 78% complicated by 90% gr 3-4 immune-related adverse events (irAEs). The phase 2 OpACIN-neo trial tested safety and efficacy of three different schemes of neoadj IPI+NIVO and identified two cycles of IPI 1mg/kg + NIVO 3mg/kg as well tolerated (20% gr 3-4 irAEs), with a high pRR of 77%. In both trials, none of the pts with a pathologic response have relapsed after a median follow-up of 30 and 8.3 months. In stage IV melanoma, long-term benefit is observed in patients achieving CR with ICI, even after cessation of therapy. This raises the question of whether a therapeutic lymph node dissection (TLND) can be omitted when a deep pathologic response with neoadj IPI+NIVO is achieved. Methods: The aim of this international multi-center investigator-initiated phase 2 PRADO extension study is to confirm the pRR and toxicity of 2 cycles of neoadjuvant IPI 1mg/kg + NIVO 3mg/kg (the preferred OPACIN-neo regimen) and to test response-driven subsequent therapy i.e. omitting surgery and adjuvant ICI based on the pathological response. 100-110 pts with stage IIIB/C melanoma and a measurable lymph node (≥15mm according to RECIST 1.1) will receive two cycles of IPI 1mg/kg + NIVO 3mg/kg after marker placement into the largest lymph node metastasis. After six weeks, pts will undergo resection of the index lymph node. For pCR/near pCR, pts will not undergo TLND; For pPR, pts will undergo TLND; and for pNR, pts will undergo TLND and start adjuvant NIVO or targeted therapy +/- radiotherapy for 52 weeks. Primary endpoints are pRR of marked lymph node and RFS at 24 months. Baseline biopsies, blood samples (week 0, 6, 12) and faeces (week 0, 6) will be collected for translational research analyses. The first patient in this trial was included in October 2018; 22 patients have been enrolled. Clinical trial information: NCT02977052.

scholarly journals Phase 2 study of perioperative chemotherapy with SOX and surgery for stage III colorectal cancer (SOS3 study)

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Naoya Aisu ◽  
Yoichiro Yoshida ◽  
Akira Komono ◽  
Ryohei Sakamoto ◽  
Daibo Kojima ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Response Rate ◽  
Disease Free Survival ◽  
Stage Iii ◽  
Perioperative Chemotherapy ◽  
Phase 2 ◽  
Primary Endpoints ◽  
Phase 2 Study ◽  
Grade 3

Abstract This phase 2 study evaluated the safety and efficacy of perioperative chemotherapy with S-1 plus oxaliplatin (SOX) for stage III colorectal cancer (CRC). Patients with stage III CRC received surgery after neoadjuvant chemotherapy (NAC; SOX 4 cycles) and adjuvant chemotherapy (AC; SOX 4 cycles). The primary endpoints were response rate and safety. We enrolled 30 patients. Their median age was 62 years (range: 43–87 years); 53% were women. They received a median of 4 cycles (range: 1–4) of NAC and a median 4 cycles (range: 0–4) of AC. Five patients interrupted NAC treatment because of toxicity (grade 3 diarrhoea [n = 1], grade 3 ileus [n = 1], and grade 3–4 thrombocytopenia [n = 3]). Patients’ responses were complete responses: n = 2 (6.6%), partial responses: n = 21 (70%), stable disease: n = 6 (20.0%), and progressive disease: n = 1 (3.3%; response rate: 73.3%). Curative resection was performed in 29 patients. No patients showed anastomotic leakage. Five-year overall survival and disease-free survival were 83.3% and 76.7%, respectively (median follow-up time: 48 months). NAC using SOX regimen is safe and effective, and may lead to reduced local recurrence and distant metastasis. Long-term outcomes are awaited to evaluate further the efficacy of this strategy (UMIN000006790).

Use of immunotherapy for stage-III and IV melanoma and likelihood of regional and distant lymph node resection and surgical resection for distant metastasis.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 9558-9558
Author(s):  
George Molina ◽  
Gyulnara G. Kasumova ◽  
Motaz Qadan ◽  
Genevieve Marie Boland
Keyword(s):  
Lymph Node ◽  
Surgical Resection ◽  
Stage Iv ◽  
Stage Iii ◽  
Median Income ◽  
Adjusted Relative Risk ◽  
Facility Type ◽  
Stage Iii Melanoma ◽  
Stratified Analysis ◽  
Stage Iv Melanoma

9558 Background: Immunotherapy (IMT) for stages-III and IV melanoma has dramatically changed overall prognosis and treatment strategies. The aim of this study was to evaluate if use of IMT significantly changed the likelihood of regional/distant lymph node (LN) resection and surgical resection for distant metastases (DM) among patients with stages-III and IV melanoma, respectively, in the pre- and post-2011 era. Methods: The National Cancer Database (2004-2015) was used to evaluate the likelihood of regional/distant LN resection and surgical resection for DM among patients with stages-III and IV melanoma, respectively, with use of IMT. Multivariable stepwise with forward selection Poisson regression with robust standard errors was used to adjust for potential confounders (age, gender, race, year of diagnosis, Charlson-Deyo Score, facility type, facility location, insurance status, 2012 median income quartile, and 2013 urban/rural status). A stratified analysis was performed to evaluate differences among facility type. Results: There were 28,847 patients (median age 62 (IQR 53-73); 36.3% female) with stage-III melanoma and 14,443 patients (median age 66 (IQR 56-76); 31.7% female) with stage-IV melanoma. Overall, 24.3% (n = 7,018) and 17.0% (n = 2,459) with stage-III and IV melanoma, respectively, received IMT. The adjusted relative risk (aRR) of regional/distant LN resection among patients with stage-III melanoma was significantly higher with use of IMT (aRR 1.16, 95% CI 1.05–1.28, P = 0.004), while the aRR of surgical resection for DM was significantly lower with use of IMT for stage-IV melanoma (aRR 0.85, 95% CI 0.78–0.92, P < 0.001). Stratified analysis demonstrated that the findings were principally reflective of academic/research hospitals. Conclusions: The higher likelihood of regional/distant LN resection in stage-III melanoma may be due to the curative role of surgery and preceded the post-MSLT-II era. Conversely, in stage-IV melanoma, surgery may be limited to resectable oligometastatic disease given the durable and systemic benefit of first-line IMT.

Ipilimumab versus placebo after complete resection of stage III melanoma: Long-term follow-up results the EORTC 18071 double-blind phase 3 randomized trial.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 2512-2512 ◽  
Author(s):  
Alexander M. M. Eggermont ◽  
Vanna Chiarion-Sileni ◽  
Jean Jacques Grob ◽  
Reinhard Dummer ◽  
Jedd D. Wolchok ◽  
...  
Keyword(s):  
Lymph Node ◽  
Complete Resection ◽  
Phase Iii ◽  
Stage Iii ◽  
Long Term Results ◽  
Double Blind ◽  
Free Survival ◽  
Stage Iii Melanoma

2512 Background: Since 2015, ipilimumab (Ipi) is an approved treatment for stage III melanoma based on a significantly (P=0.0013) prolonged recurrence-free survival (RFS) (Eggermont et al, Lancet Oncology, 2015). At a median follow-up of 5.3 years, RFS (HR=0.76) and distant metastasis-free survival (DMFS) (HR=0.76), assessed by an IRC, and overall survival (OS) (HR=0.72) were prolonged in the Ipi group as compared to the placebo (Pbo) group (Eggermont et al, NEJM, 2016), despite a 53.3% (Ipi) vs 4.6% (Pbo) treatment discontinuation rate due to adverse events. Methods: In this randomized double-blind trial, eligible patients (pts) included those ≥18 yrs of age who underwent complete resection of stage III cutaneous melanoma (excluding lymph node metastasis ≤1 mm or in-transit metastasis). 951 pts were randomized (stratified by stage and region) 1:1 to Ipi 10 mg/kg (n=475) or placebo (Pbo, n=476) q3w for 4 doses, then every 3 mos for up to 3 yrs until completion, disease recurrence, or unacceptable toxicity. Here, we report the comparison between the Ipi and Pbo groups regarding the long-term efficacy outcomes using the local investigator assessments. Results: Overall, 20%/44%/36% of pts had AJCC-7 stage IIIA/IIIB/IIIC, 42% ulcerated primary, and 58% macroscopic lymph node involvement. Median follow-up was 6.9 yrs. The RFS, DMFS and OS benefit observed in the Ipi group was long-lasting (almost 10% difference at 7 years) and consistent across subgroups: no significant predictive factors could be detected. Conclusions: In this phase III trial, Ipi, administered at 10 mg/kg, as adjuvant therapy provided, at a 6.9 yr median follow-up, a sustained improvement in the RFS, DMFS, and OS long-term results in patients with high-risk stage III melanoma. Clinical trial information: NCT00636168. [Table: see text]

Camrelizumab plus chemotherapy as neoadjuvant therapy for resectable, locally advanced esophageal squamous cell carcinoma (NIC-ESCC2019): A multicenter, open-label, single-arm, phase 2 study.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 4028-4028
Author(s):  
Jingpei Li ◽  
Jun Liu ◽  
Zhuoyi Li ◽  
Fei Cui ◽  
Yuan Zeng ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Squamous Cell Carcinoma ◽  
Neoadjuvant Chemotherapy ◽  
Esophageal Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Primary Tumor ◽  
Pathologic Response ◽  
Pathological Response ◽  
Phase 2 ◽  
Phase 2 Study

4028 Background: Despite multidisciplinary therapies, prognosis of pts with resectable esophageal squamous cell carcinoma (ESCC) remains poor. Combining PD-1 blockade to neoadjuvant chemotherapy might be a feasible and effective strategy. Camrelizumab (an anti-PD-1 antibody) was approved for advanced or metastatic ESCC in the second-line setting and showed improved anti-tumor activity and survival benefit when combined with chemotherapy in multiple advanced tumors. Methods: In this NIC-ESCC2019 phase 2 study, histologically or cytologically confirmed ESCC pts (stage II-IVA) were enrolled to receive two cycles of neoadjuvant chemoimmunotherapy (NIC) with camrelizumab (200 mg on day 1) plus nab-paclitaxel (260 mg/m² in total on day 1 and day 8) and cisplatin (75 mg/m² in total on days 1-3) of each 21-day cycle, followed by esophagectomy. The primary endpoint was complete pathologic response (CPR) rate in the primary tumor. Besides, we also explored the relationship between the tumor genomic profile or primary-tumor microenvironment and the pathological response. Results: Between Jan 17, 2020 and Dec 8, 2020, 56 pts were enrolled. 51 pts underwent surgical resection, and all had complete tumor resection. CPR was achieved in 18 (35.3%; 95% CI, 21.7%-48.9%) pts; 12 (23.5%) pts had major pathologic response (MPR), and 21 (41.2%) had incomplete pathological response (IPR). Of note, 16 (31.4%) pts achieved CPR in both primary tumor and lymph nodes. The objective response rate was 66.7% (95% CI, 40.0-70.4). No in-hospital mortality occurred. The most common treatment-related adverse events (TRAEs) were decreased WBC (20 [36%] of 56 pts), vomiting (19 [34%]), and alopecia (18 [32%]). Grade 3 TRAEs only occurred in 6 (11%) pts, and there were no grade 4 or 5 TRAEs. The most common immune-related AEs included grade 1-2 rash maculo-papular (7 [13%]) and reactive cutaneous capillary endothelial proliferation (5 [9%]). Presence of mutations in CREBBP and KMT2D at treatment-naïve time-point was correlated with non-response group (IPR and stable disease) (CREBBP, p = 0.046; KMT2D, p = 0.047). Among the immune populations, CD8+, CD8+PD-1+ and CD8+PD-L1+ T cells increased significantly after two doses of NIC, especially in the CPR+MPR group (CD8+, p = 0.013; CD8+PD-1+, p < 0.001; CD8+PD-L1+, p = 0.068). Conclusions: The addition of camrelizumab to neoadjuvant chemotherapy in ESCC demonstrated promising efficacy with acceptable toxicity, supporting the further investigation in a randomized phase 3 clinical trial. Clinical trial information: NCT04225364. [Table: see text]

Neoadjuvant and adjuvant nivolumab (nivo) with anti-LAG3 antibody relatlimab (rela) for patients (pts) with resectable clinical stage III melanoma.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 9502-9502
Author(s):  
Rodabe Navroze Amaria ◽  
Michael A. Postow ◽  
Michael T. Tetzlaff ◽  
Merrick I. Ross ◽  
Isabella Claudia Glitza ◽  
...  
Keyword(s):  
Adjuvant Treatment ◽  
Clinical Stage ◽  
Pathologic Response ◽  
Stage Iii ◽  
Toxicity Profile ◽  
Radiographic Response ◽  
Recist 1.1 ◽  
Viable Tumor ◽  
Stage Iii Melanoma ◽  
Favorable Toxicity Profile

9502 Background: Neoadjuvant therapy (NT) for pts with clinical stage III melanoma remains an active area of research interest. Recent NT trial data demonstrates that achieving a pathologic complete response (pCR) correlates with improved relapse-free (RFS) and overall survival (OS). Checkpoint inhibitor (CPI) NT with either high or low dose ipilimumab and nivolumab regimens produces a high pCR rate of 30-45% but with grade 3-4 toxicity rate of 20-90%. In metastatic melanoma (MM), the combination of nivo with rela (anti Lymphocyte Activation Gene-3 antibody) has demonstrated a favorable toxicity profile and responses in both CPI-naïve and refractory MM. We hypothesized that NT with nivo + rela will safely achieve high pCR rates and provide insights into mechanisms of response and resistance to this regimen. Methods: We conducted a multi-institutional, investigator-initiated single arm study (NCT02519322) enrolling pts with clinical stage III or oligometastatic stage IV melanoma with RECIST 1.1 measurable, surgically-resectable disease. Pts were enrolled at 2 sites and received nivo 480mg IV with rela 160mg IV on wks 1 and 5. Radiographic response (RECIST 1.1) was assessed after completion of NT; surgery was conducted at wk 9 and specimens were assessed for pathologic response per established criteria. Pts received up to 10 additional doses of nivo and rela after surgery, with scans every 3 mo to assess for recurrence. The primary study objective was determination of pCR rate. Secondary objectives included safety, radiographic response by RECIST 1.1, event-free survival (EFS), RFS, and OS analyses. Blood and tissue were collected at baseline, at day 15, day 28, and at surgery for correlative analyses. Results: A total of 30 pts (19 males, median age 60) were enrolled with clinical stage IIIB/IIIC/IIID/IV (M1a) in 18/8/2/2 pts, respectively. 29 pts underwent surgery; 1 pt developed distant metastatic disease while on NT. pCR rate was 59% and near pCR ( < 10% viable tumor) was 7% for a major pathologic response (MPR, pCR + near pCR) of 66%. 7% of pts achieved a pPR (10-50% viable tumor) and 27% pNR (≥50% viable tumor). RECIST ORR was 57%. With a median follow up of 16.2 mos, the 1 -year EFS was 90%, RFS was 93%, and OS was 95%. 1-year RFS for MPR was 100% compared to 80% for non-MPR pts (p = 0.016). There were no treatment related gr 3/4 AEs that arose during NT; 26% of pts had a gr 3/4 AE that began during adjuvant treatment. Conclusions: Neoadjuvant and adjuvant treatment with nivo and rela achieved high pCR and MPR rates with a favorable toxicity profile in the neoadjuvant and adjuvant settings. Pts with MPR had improved outcomes compared to non-MPR pts. Translational studies to discern mechanisms of response and resistance to this combination are underway. Clinical trial information: NCT02519322.

scholarly journals Completely resected stage III melanoma controversy - 15 years of national tertiary centre experience

2020 ◽  
Vol 0 (0) ◽  
Author(s):  
Barbara Peric ◽  
Sara Milicevic ◽  
Andraz Perhavec ◽  
Marko Hocevar ◽  
Janez Zgajnar
Keyword(s):  
Lymph Node ◽  
Sentinel Lymph Node ◽  
Rapid Development ◽  
Primary Tumour ◽  
Stage Iii ◽  
Unknown Primary ◽  
Tertiary Centre ◽  
Kaplan Meier ◽  
Stage Iii Melanoma ◽  
Resected Stage

AbstractBackgroundTwo prospective randomized studies analysing cutaneous melanoma (CM) patients with sentinel lymph node (SLN) metastases and rapid development of systemic adjuvant therapy have changed our approach to stage III CM treatment. The aim of this study was to compare results of retrospective survival analysis of stage III CM patients’ treatment from Slovenian national CM register to leading international clinical guidelines.Patients and methodsSince 2000, all Slovenian CM patients with primary tumour ≥ TIb are treated at the Institute of Oncology Ljubljana and data are prospectively collected into a national CM registry. A retrospective analysis of 2426 sentinel lymph node (SLN) biopsies and 789 lymphadenectomies performed until 2015 was conducted using Kaplan-Meier survival curves and log-rank tests.ResultsPositive SLN was found in 519/2426 (21.4%) of patients and completion dissection (CLND) was performed in 455 patients. The 5-year overall survival (OS) of CLND group was 58% vs. 47% of metachronous metastases group (MLNM) (p = 0.003). The 5-year OS of patients with lymph node (LN) metastases and unknown primary site (UPM) was 45% vs. 21% of patients with synchronous LN metastasis. Patients with SLN tumour burden < 0.3 mm had 5-year OS similar to SLN negative patients (86% vs. 85%; p = 0.926). The 5-year OS of patients with burden > 1.0 mm was similar to the MLNM group (49% vs. 47%; p = 0.280).ConclusionsStage III melanoma patients is a heterogeneous group with significant OS differences. CLND after positive SLNB might still remain a method of treatment for selected patients with stage III.

Long-term results of surgical treatment of gastric cancer

1986 ◽  
Vol 67 (2) ◽  
pp. 104-106
Author(s):  
A. S. Abdullin ◽  
F. Sh. Akhmetzyanov ◽  
A. A. Samigullin ◽  
Z. N. Shemeunova ◽  
V. A. Arinin ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Surgical Treatment ◽  
Stomach Cancer ◽  
Stage Iv ◽  
Stage Ii ◽  
Stage Iii ◽  
Disease Stage ◽  
Long Term Results ◽  
Long Term Outcomes

We analyzed long-term outcomes of the treatment of 217 patients (men - 126, women - 91), who underwent radical operations for stomach cancer in the period of 1972 till 1976. 14 patients were under 39, 52 - from 40 to 49, 50 to 59 - 52, 60 to 69 - 80, over 70 years old - 19. The youngest patient was 28 years old and the oldest - 76 years old. Most patients (185) were operated on at stage III of the disease, stage II was diagnosed in 27 patients, and stage IV - in 5 patients.

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