scholarly journals PCN245 GRADE 3/4 ADVERSE EVENT (AE) COSTS OF NIVOLUMAB VERSUS DABRAFENIB + TRAMETINIB AS ADJUVANT TREATMENT IN PATIENTS WITH STAGE III BRAF-MUTATED CUTANEOUS MELANOMA IN PORTUGAL

2019 ◽  
Vol 22 ◽  
pp. S483 ◽  
Author(s):  
D. Alves ◽  
A. Amadi ◽  
A. Moshyk ◽  
K. Betts ◽  
E.X. Du
Keyword(s):  
Adverse Event ◽  
Adjuvant Treatment ◽  
Cutaneous Melanoma ◽  
Stage Iii ◽  
Grade 3

Neoadjuvant ipilimumab + nivolumab (IPI+NIVO) in palpable stage III melanoma: Updated data from the OpACIN trial and first immunological analyses.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 9586-9586 ◽  
Author(s):  
Elisa A. Rozeman ◽  
Christian U. Blank ◽  
Alexander Christopher Jonathan Van Akkooi ◽  
Pia Kvistborg ◽  
Lorenzo Fanchi ◽  
...  
Keyword(s):  
T Cell ◽  
High Risk ◽  
Adjuvant Treatment ◽  
Stage Iv ◽  
Study Data ◽  
Stage Iii ◽  
Feasibility Trial ◽  
Melanoma Patients ◽  
Stage Iii Melanoma ◽  
Grade 3

9586 Background: The combination of IPI+NIVO induces high response rates and improved overall survival in late stage melanoma. T cell checkpoint inhibition is of greatest value at the moment of TCR triggering and therefore dependent on the amount of antigen present, indicating that adjuvant immunotherapy may work most efficiently, when initiated prior to surgery. Methods: Two-arm Phase 1b feasibility trial of 20 high risk AJCC stage IIIB and IIIC melanoma patients with palpable nodal disease receiving the combination of IPI 3mg/kg and NIVO 1mg/kg, either adjuvant four courses after surgery, or split two courses neo-adjuvant and two courses adjuvant. Results: In this update all 20 patients are evaluable. Neo-adjuvant application of IPI+NIVO was feasible and no surgery-associated adverse events were attributed to (neo-)adjuvant therapy. 18/20 patients had to stop early due to grade 3/4 toxicities. Neo-adjuvant IPI+NIVO reduced tumor load in 8/10 patients (3 pCR, 4 near-pCRs [minimal remaining micrometastases], 1 pPR [75% reduction], 1 SD and 1 PD). To date, after a median follow-up of 45 weeks (range 13-74), none of the responders in the neoadjuvant arm has relapsed. Relapse was observed for both non-responders within the neo-adjuvant arm and for 3 patients within the adjuvant arm. TCR sequencing and MHC tetramer-based analysis to compare the induction and expansion of tumor (neo-)antigen-specific T cell responses between both treatment arms are underway and will be presented. Conclusions: The combination of IPI+NIVO in the (neo-)adjuvant treatment setting for high risk stage III melanoma patients is feasible and induces very frequent responses. At the same time, severe grade 3/4 toxicity is more frequent than expected from stage IV melanoma patient study data. These results indicate that IPI+NIVO is a promising combination for neo-adjuvant treatment in stage III melanoma. Adjusted combination schemes are currently tested in the phase 2 OpACIN-neo trial, with the aim of reducing toxicity while preserving efficacy. Clinical trial information: NCT02437279.

Impact of age and medical comorbidity (MC) on adjuvant treatment outcomes for stage III colon cancer (CC): A pooled analysis of individual patient data from four randomized controlled trials.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 3522-3522 ◽  
Author(s):  
Daniel G. Haller ◽  
Michael O'Connell ◽  
Thomas H. Cartwright ◽  
Christopher Twelves ◽  
Edward McKenna ◽  
...  
Keyword(s):  
Treatment Outcomes ◽  
Adjuvant Treatment ◽  
Cox Regression ◽  
Age Groups ◽  
Sensory Neuropathy ◽  
Pooled Analysis ◽  
Stage Iii ◽  
Regression Analyses ◽  
Grade 3 ◽  
The Impact

3522 Background: Studies show significantly improved disease-free and overall survival (DFS, OS) for oxaliplatin (Ox)-based vs. leucovorin/5-fluorouracil (LV/5-FU) adjuvant therapy in CC, with conflicting reports of Ox benefit in patients > 70 years old. The impact of MC on Ox benefit has not been assessed. We assessed the impact of age and MC on adjuvant treatment outcomes for stage III CC. Methods: N = 4,819 patients from NSABP C-08, XELOXA, X-ACT, and AVANT were analyzed by Ox therapy (XELOX/FOLFOX) vs. LV/5-FU, MC, and age; patients treated with bevacizumab were excluded. Endpoints were DFS (primary), OS, and safety. MC was assessed (except NSABP C-08) by adapted Charlson Comorbidity and NCI Combined Indices (CCI, NCI): Low (≤ 1) vs. high (> 1). Hazardratios (HR) were estimated by Cox regression analyses. Multivariate Cox regression analyses (MVA) tested for independent effects of age and MC on Ox benefit, controlling for gender, T, and N stage. Results: Patient demographics, MC, and disease characteristics (except lymph nodes examined) were well balanced across groups. Median follow-up was shorter in NSABP C-08 and AVANT (36 and 50 months) vs. XELOXA and X-ACT (83 and 74 months). MVA-confirmed DFS/OS benefit was consistently shown for XELOX/FOLFOX vs. LV/5-FU, regardless of age or MC. Grade 3/4 serious adverse event (AE) rates were comparable across cohorts and CCI scores, and higher in patients aged ≥ 70. Grade 3/4 AEs of interest, including peripheral sensory neuropathy, were comparable across ages and CCI scores, and higher with XELOX/FOLFOX. Conclusions: Ox benefit is modestly attenuated in patients aged ≥ 70; however, significant benefit is observed regardless of age or MC in this analysis. Our results further support XELOX or FOLFOX as standard options for the adjuvant management of stage III CC in all age groups. [Table: see text]

Improved Overall Survival With Oxaliplatin, Fluorouracil, and Leucovorin As Adjuvant Treatment in Stage II or III Colon Cancer in the MOSAIC Trial

2009 ◽  
Vol 27 (19) ◽  
pp. 3109-3116 ◽  
Author(s):  
Thierry André ◽  
Corrado Boni ◽  
Matilde Navarro ◽  
Josep Tabernero ◽  
Tamas Hickish ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Overall Survival ◽  
Adjuvant Treatment ◽  
Disease Free Survival ◽  
Sensory Neuropathy ◽  
Stage Ii ◽  
Stage Iii ◽  
Curative Intent ◽  
Grade 3 ◽  
Peripheral Sensory

Purpose Three-year disease-free survival (DFS) was significantly improved in patients who had undergone resection with curative intent for stage II or III colon cancer who received bolus plus continuous-infusion fluorouracil plus leucovorin (LV5FU2) with the addition of oxaliplatin (FOLFOX4). Final results of the study, including 6-year overall survival (OS) and 5-year updated DFS, are reported. Patients and Methods A total of 2,246 patients were randomly assigned to receive LV5FU2 or FOLFOX4 for 6 months. The primary end point was DFS. Secondary end points were OS and safety. Results Five-year DFS rates were 73.3% and 67.4% in the FOLFOX4 and LV5FU2 groups, respectively (hazard ratio [HR] = 0.80; 95% CI, 0.68 to 0.93; P = .003). Six-year OS rates were 78.5% and 76.0% in the FOLFOX4 and LV5FU2 groups, respectively (HR = 0.84; 95% CI, 0.71 to 1.00; P = .046); corresponding 6-year OS rates for patients with stage III disease were 72.9% and 68.7%, respectively (HR = 0.80; 95% CI, 0.65 to 0.97; P = .023). No difference in OS was seen in the stage II population. The incidence of second noncolorectal cancers was 5.5% and 6.1% in the FOLFOX4 and LV5FU2 groups, respectively. Among patients receiving oxaliplatin, the frequency of grade 3 peripheral sensory neuropathy was 1.3% 12 months after treatment and 0.7% at 48 months. Conclusion Adding oxaliplatin to LV5FU2 significantly improved 5-year DFS and 6-year OS in the adjuvant treatment of stage II or III colon cancer and should be considered after surgery for patients with stage III disease.

scholarly journals Superficial and deep lymph node dissection for stage III cutaneous melanoma: clinical outcome and prognostic factors

2013 ◽  
Vol 11 (1) ◽  
pp. 36 ◽  
Author(s):  
Nicola Mozzillo ◽  
Corrado Caracò ◽  
Ugo Marone ◽  
Gianluca Di Monta ◽  
Anna Crispo ◽  
...  
Keyword(s):  
Prognostic Factors ◽  
Lymph Node ◽  
Clinical Outcome ◽  
Lymph Node Dissection ◽  
Cutaneous Melanoma ◽  
Stage Iii ◽  
Node Dissection

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 Tumor-derived interleukin-10 as a prognostic factor in stage III patients undergoing adjuvant treatment with an autologous melanoma cell vaccine

2011 ◽  
Vol 60 (7) ◽  
pp. 1039-1045 ◽  
Author(s):  
Amit Mahipal ◽  
Mizue Terai ◽  
David Berd ◽  
Inna Chervoneva ◽  
Kashyap Patel ◽  
...  
Keyword(s):  
Prognostic Factor ◽  
Melanoma Cell ◽  
Adjuvant Treatment ◽  
Interleukin 10 ◽  
Stage Iii ◽  
Cell Vaccine

scholarly journals Molecular alterations in clinical stage III cutaneous melanoma: Correlation with clinicopathological features and patient outcome

2014 ◽  
Vol 8 (1) ◽  
pp. 47-54 ◽  
Author(s):  
PIOTR RUTKOWSKI ◽  
ALEKSANDRA GOS ◽  
MONIKA JURKOWSKA ◽  
TOMASZ ŚWITAJ ◽  
WIRGINIUSZ DZIEWIRSKI ◽  
...  
Keyword(s):  
Patient Outcome ◽  
Cutaneous Melanoma ◽  
Clinical Stage ◽  
Clinicopathological Features ◽  
Stage Iii ◽  
Molecular Alterations

scholarly journals Safety Profile of Idelalisib in Patients with Refractory Follicular Lymphoma: Interim Analysis of a Noninterventional Study

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 48-50
Author(s):  
Gilles Salles ◽  
Ka Lung Wu ◽  
Sofya Kovalchuk ◽  
Santiago Mercadal ◽  
Annalisa Chiarenza ◽  
...  
Keyword(s):  
Follicular Lymphoma ◽  
Safety Profile ◽  
Interim Analysis ◽  
Research Funding ◽  
Stage Iii ◽  
Disease Stage ◽  
Stevens Johnson Syndrome ◽  
Risk Of Death ◽  
Registration Trial ◽  
Grade 3

Introduction: Idelalisib, a selective oral inhibitor of PI3Kδ, was approved by the FDA and EMA as monotherapy for patients with advanced follicular lymphoma (FL) based on positive efficacy and safety results from the registration phase 2 trial in patients with indolent non-Hodgkin lymphoma (iNHL) refractory to 2 prior regimens (NCT01282424; 101-09). Phase 3 studies of idelalisib in earlier lines of treatment for iNHL were terminated prematurely due to an increased risk of death and higher incidence of serious adverse events (AEs) associated with idelalisib. Herein, we present the preplanned interim results as of June 8, 2020, of the safety of idelalisib monotherapy in patients with refractory FL treated in the EU from one of the largest noninterventional trials of idelalisib. Methods: This was a noninterventional, partially retrospective cohort study conducted in 10 European countries (EUPAS19618; NCT03568929). Eligible patients were adults aged ≥18 years treated with idelalisib for refractory FL, per the Summary of Product Characteristics and treatment guidelines, in routine clinical practice. Data was collected from patients' medical records and anonymized. Safety events were evaluated and included treatment-emergent AEs (TEAEs), health outcomes of interest (HOIs) requested by the EMA (bowel perforations, Grade ≥3 diarrhea/colitis, progressive multifocal leukoencephalopathy, pneumonitis, Grade ≥3 rash, infections, Stevens-Johnson syndrome, transaminase elevations, and hepatocellular injury), and deaths. TEAEs were defined as AEs that occurred between first dose and 30 days after last dose. Data were summarized using descriptive statistics. Rates per person-year were calculated as the number of patients experiencing an AE divided by the person-time at risk. Results: For the 158 patients included in this analysis, median age was 67 years and 84 (53%) were male. A summary of patient and disease characteristics at baseline are presented in Table 1. At treatment initiation, 47 (30%) patients had grade 2 FL and 105 (66%) had Ann Arbor stage III/IV disease, though these characteristics were not captured for 42% and 20% of patients, respectively; 149 (94%) had ≥2 prior therapies. The median duration of idelalisib exposure was 165 (range 11-1321) days, and patients were observed for a median of 323 (range 12-1676) days. In total, 144 (91%) patients experienced a TEAE, with a rate of 3.36 per person-year. The proportion of patients experiencing Grade 3/4, severe, common, and HOI TEAEs are presented in Table 2. Diarrhea of any grade was the most common TEAE, and infections were the most common treatment-emergent HOI. During the TEAE period, 19 (12%) patients died (Table 2). The proportion of common TEAEs reported in this analysis were lower compared with a subgroup analysis of patients with FL from the registration trial (Salles Haematologica 2017; DOI: 10.3324/haematol.2016.151738), including diarrhea 27% vs 51%, cough 9% vs 32%, fever/pyrexia 10% vs 29%, pneumonia 5% vs 11%; treatment-emergent Grade 3/4 diarrhea/colitis and transaminase elevations were also lower in this analysis: 8% vs 17% and 4% vs 14%. This comparison is limited due to differences in study populations, namely that patients in the registration trial had more advanced disease (stage III/IV, 66% vs 83%) and had a higher median number of prior therapies (3 vs 4). Conclusions: This interim analysis of the safety of idelalisib in patients with refractory FL in this large noninterventional safety study provides an estimate of potential final study findings. The AE profile from this study appears to corroborate the known safety profile of idelalisib. No new safety signals were detected. Disclosures Salles: Bristol Myers Squibb: Consultancy, Other; Genmab: Consultancy; Gilead: Consultancy, Honoraria, Other: Participation in educational events; Epizyme: Consultancy; Abbvie: Consultancy, Honoraria, Other: Participation in educational events; Autolus: Consultancy; Amgen: Honoraria, Other: Participation in educational events; Celgene: Consultancy, Honoraria, Other: Participation in educational events; Debiopharm: Consultancy; Takeda: Consultancy, Honoraria, Other; Novartis: Consultancy, Honoraria, Other; F. Hoffman-La Roche Ltd: Consultancy, Honoraria, Other; Janssen: Consultancy, Honoraria, Other: Participation in educational events; Karyopharm: Consultancy; Kite: Consultancy, Honoraria, Other; MorphoSys: Consultancy, Honoraria, Other. Pettengell:Celgene: Honoraria; MEI Pharma: Honoraria; Roche Ltd: Honoraria; Takeda: Honoraria. Vandenberghe:Celgene: Other: sponsorship to attend Lugano lymphoma meeting in 2019; Abbvie: Other: travel grants, Research Funding; Gilead: Other: travel grants, Research Funding; Janssen: Other: travel grants; Roche: Other: travel grants, Research Funding. Corradini:Kiowakirin: Consultancy, Honoraria; Incyte: Consultancy; Gilead: Consultancy, Honoraria, Other; F. Hoffman-La Roche Ltd: Consultancy, Honoraria; Daiichi Sankyo: Consultancy, Honoraria; Celgene: Consultancy, Honoraria, Other; BMS: Other; Servier: Consultancy, Honoraria; Sanofi: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Amgen: Consultancy, Honoraria, Other; Kite: Consultancy, Honoraria; Novartis: Consultancy, Honoraria, Other; Takeda: Consultancy, Honoraria, Other; AbbVie: Consultancy, Honoraria, Other. De Belder:Gilead Sciences Europe, Ltd.: Current Employment. Shah Gupta:Gilead Sciences, Ltd.: Current Employment. van Troostenburg:Gilead Sciences GmbH: Current Employment. Rajakumaraswamy:Gilead Sciences, Inc.: Current Employment. Ramroth:Gilead Sciences, Ltd.: Current Employment.

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