Molecular marker assessments for epidermal growth factor receptor (EGFR) expression by immunohistochemistry (IHC) and histoscore (H-score) in the phase III SELECT trial.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 8052-8052
Author(s):  
Edward S. Kim ◽  
Sreenivas Chittoor ◽  
Craig H. Reynolds ◽  
Lorinda Simms ◽  
Scott Saxman
Keyword(s):  
Growth Factor Receptor ◽  
Progression Free Survival ◽  
Clinical Results ◽  
Phase Iii ◽  
Egfr Expression ◽  
Phase Iii Study ◽  
Previously Treated Patients ◽  
Previously Treated ◽  
Epidermal Growth ◽  
Select Trial

8052 Background: SELECT was a phase III study that investigated whether the addition of cetuximab (C) to pemetrexed (P) improved outcome in previously treated patients (pts) with recurrent or progressive non-small cell lung cancer (NSCLC). Clinical results have been reported previously and demonstrated that adding C to P did not improve progression-free survival (PFS) or overall survival (OS). H-score has been reported to be a potential predictor of outcome for C therapy. Prespecified biomarker analyses, including EGFR IHC and H-score, are reported here. Methods: EGFRexpression in tumor tissue was not required for eligibility; however, tissue was collected and analyzed for EGFR expression by IHC using standard methods. In addition, H-score evaluation was performed by trained central pathologists and correlated with clinical outcome using a predefined cutoff for “low” and “high” of <200 and ≥200, respectively. Results: A total of 449 (IHC) and 406 (H-score) pt specimens were evaluable. Demographics for pts with tissue available for EGFR analysis were similar to the overall population. For IHC+ pts (n=396), median PFS for C+P was 3.02 months (95% CI, 2.76–3.45) compared with 2.99 months (95% CI, 2.63–4.14) for P (HR, 1.02 [95% CI, 0.83–1.24]; p=.86). For pts with low H-score (N=99 [C+P] and N=111 [P]), median PFS was 2.7 months (95% CI, 1.8–3.2) with C+P and 3.1 months (95% CI, 2.6–4.1) with P (HR, 1.11 [95% CI, 0.84–1.46]; P=.48); median OS was 6.7 months (95% CI, 5.3–8.6) with C+P and 6.6 months (95% CI, 4.7–9.2) with P (HR, 0.96 [95% CI, 0.72–1.27]; P=.76). Among pts with high H-scores (N=101 [C+P] and N= 95 [P]), median PFS was 3.2 months (95% CI, 2.7–4.6) with C+P and 3.7 months (95% CI, 1.7–4.5) with P (HR, 1.02 [95% CI, 0.77–1.37]; P=.86); median OS was 7.7 months (95% CI, 6.5–10.9) with C+P and 8.0 months (95% CI, 7.0–9.1) with P (HR, 1.17 [95% CI, 0.86–1.57]; P=.32). Conclusions: EGFR H-score was not predictive of benefit for the addition of C to P in this population of pts with NSCLC. There was also no treatment effect in the IHC+ group. Clinical trial information: NCT00095199.

Phase III study of irinotecan/5FU/LV (FOLFIRI) or oxaliplatin/5FU/LV (FOLFOX) ± cetuximab for patients (pts) with untreated metastatic adenocarcinoma of the colon or rectum (MCRC): CALGB 80203 preliminary results

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 3509-3509 ◽  
Author(s):  
A. Venook ◽  
D. Niedzwiecki ◽  
D. Hollis ◽  
S. Sutherland ◽  
R. Goldberg ◽  
...  
Keyword(s):  
Performance Status ◽  
Growth Factor Receptor ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Chi Square ◽  
Duration Of Response ◽  
Phase Iii Study ◽  
Epidermal Growth ◽  
Adenocarcinoma Of The Colon ◽  
C 32

3509 Background: FOLFIRI or FOLFOX are 1st-line treatments (Rx) for MCRC. Cetuximab is an IgG1 Mab that targets the epidermal growth factor receptor (EGFR) and is approved as monotherapy or in combination with irinotecan in irinotecan-refractory, EGFR + pts with MCRC. CALGB 80203 randomized untreated MCRC pts to FOLFOX or FOLFIRI ± cetuximab (independent of EGFR status.) Methods: Pts with performance status 0–1 with tumor blocks available for EGFR analysis received either irinotecan 180 mg/m2 over 1.5 hours (h) or oxaliplatin 85 mg/m2 over 2h combined with LV 400 mg/m2 over 2h and 5FU 400 mg/m2 bolus, then 46–48h CI 5FU 2400 mg/m2 q o w. Cetuximab dose: 400 mg/m2 loading dose, then 250 mg/m2 qw. Rx continued until progression or toxicity; subsequent Rx was not mandated although information was collected on such rx. Accrual goal was 2200 pts with intended 1° endpt of overall survival (OS). 80203 closed administratively in 1/05 (due to slow accrual) with 238 pts accrued. 2° endpts of response rate (RR), progression free survival (PFS), duration of R and toxicity are now able to be analyzed. Results: Accrual: FOLFIRI (A) - 61; FOLFIRI + cetuximab (B) - 59: FOLFOX (C) - 60; FOLFOX + cetuximab (D) - 58; approx median follow-up (f/u) is 12 months. RR (CR + PR, not all yet confirmed): A - 34%; B - 42%; C - 32%; D - 55%. RR was similar in the FOLFIRI or FOLFOX arms (A+B v. C+D; 38% v. 43%, p=0.44; chi-square) while C225 containing arms (B+D) v. non-C225 arms (A+C) had a superior RR (49% v. 33%; p=0.014, chi-square) It is too early to tell if there are differences in PFS, duration of response or OS. No significant differences in gr III diarrhea or any gr IV toxicities were seen. Conclusions: These results suggest that FOLFIRI and FOLFOX are similar in efficacy for pts with untreated MCRC and that adding cetuximab to either in1st-line Rx appears to increase response rates. PFS and duration of response do not appear different at this analysis. Further f/u and an analysis of prospective companion correlative studies may help to further clarify these results. [Table: see text]

scholarly journals Pain Progression at Initiation of Cabazitaxel in Metastatic Castration-Resistant Prostate Cancer (mCRPC): A Post Hoc Analysis of the PROSELICA Study

Cancers ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1284
Author(s):  
Nicolas Delanoy ◽  
Debbie Robbrecht ◽  
Mario Eisenberger ◽  
Oliver Sartor ◽  
Ronald de Wit ◽  
...  
Keyword(s):  
Progression Free Survival ◽  
Phase Iii ◽  
Castration Resistant Prostate Cancer ◽  
Radiological Progression ◽  
Post Hoc Analysis ◽  
Psa Response ◽  
Phase Iii Study ◽  
Psa Progression ◽  
Previously Treated ◽  
Post Hoc

Background: In the PROSELICA phase III trial (NCT01308580), cabazitaxel 20 mg/m2 (CABA20) was non-inferior to cabazitaxel 25 mg/m2 (CABA25) in mCRPC patients previously treated with docetaxel (DOC). The present post hoc analysis evaluates how the type of progression at randomization affected outcomes. Methods: Progression type at randomization was defined as follows: PSA progression only (PSA-p; no radiological progression (RADIO-p), no pain), RADIO-p (±PSA-p, no pain), or pain progression (PAIN-p, ±PSA-p, ±RADIO-p). Relationships between progression type and overall survival (OS), radiological progression-free survival (rPFS), and PSA response (confirmed PSA decrease ≥ 50%) were analyzed. Results: All randomized patients (n = 1200) had received prior DOC, and 25.7% had received prior abiraterone or enzalutamide. Progression type at randomization was evaluable in 1075 patients (PSA-p = 24.4%, RADIO-p = 20.8%, PAIN-p = 54.8%). Pain progression was associated with clinical and biological features of aggressive disease. Median OS from CABA initiation or date of mCRPC diagnosis, all arms combined, was shorter in the PAIN-p group than in the RADIO-p or the PSA-p groups (12.0 versus 16.8 and 18.4 months, respectively, p < 0.001). In multivariate analysis, all arms combined, PAIN-p was an independent predictor of poor OS (HR = 1.44, p < 0.001). PSA response, rPFS, and OS were numerically higher with CABA25 versus CABA20 in patients with PAIN-p. Conclusions: This post hoc analysis of the PROSELICA phase III study shows that pain progression at initiation of CABA in mCRPC patients previously treated with DOC is associated with a poor prognosis. Disease progression should be carefully monitored, even in the absence of PSA rise.

Nivolumab (NIVO) plus ipilimumab (IPI) or NIVO plus chemotherapy (chemo) versus chemo as first-line (1L) treatment for advanced esophageal squamous cell carcinoma (ESCC): First results of the CheckMate 648 study.

2021 ◽  
Vol 39 (18_suppl) ◽  
pp. LBA4001-LBA4001
Author(s):  
Ian Chau ◽  
Yuichiro Doki ◽  
Jaffer A. Ajani ◽  
Jianming Xu ◽  
Lucjan Wyrwicz ◽  
...  
Keyword(s):  
Tumor Cell ◽  
Objective Response ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Primary Endpoints ◽  
First Results ◽  
Duration Of Response ◽  
Secondary Endpoints ◽  
Phase Iii Study ◽  
Previously Treated Patients

LBA4001 Background: NIVO demonstrated superior overall survival (OS) vs chemo in previously treated patients (pts) with ESCC (ATTRACTION-3). We report OS and progression-free survival (PFS) from CheckMate 648, the first global phase III study to evaluate both an immuno-oncology (I-O)/chemo combination and an I-O/I-O combination in advanced ESCC. Methods: Adults with previously untreated, unresectable advanced, recurrent or metastatic ESCC were enrolled regardless of tumor cell PD-L1 expression. Pts were randomized to NIVO (240 mg Q2W) + chemo (fluorouracil + cisplatin Q4W), NIVO (3 mg/kg Q2W) + IPI (1 mg/kg Q6W), or chemo alone. Primary endpoints for both comparisons were OS and PFS per blinded independent central review (BICR) in pts with tumor cell PD-L1 ≥ 1%. Hierarchically tested secondary endpoints included OS and PFS in all randomized pts. Results: 970 pts were randomized to NIVO + chemo, NIVO + IPI, and chemo arms (49% with tumor cell PD-L1 ≥ 1%). With 13 months (mo) minimum follow-up, NIVO + chemo and NIVO + IPI led to statistically significant improvement in OS vs chemo in pts with tumor cell PD-L1 ≥ 1% and all randomized pts (Table). Statistically significant PFS benefit was also observed for NIVO + chemo vs chemo (HR 0.65 [98.5% CI 0.46–0.92]; P = 0.0023) in pts with tumor cell PD-L1 ≥ 1%. PFS in NIVO + IPI vs chemo in pts with tumor cell PD-L1 ≥ 1% did not meet the prespecified boundary for significance. The objective response rate (per BICR) was 53% (NIVO + chemo), 35% (NIVO + IPI), and 20% (chemo) in pts with tumor cell PD-L1 ≥ 1% and in all randomized pts was 47%, 28%, and 27%, respectively; longer median (95% CI) duration of response was observed vs chemo for pts with tumor cell PD-L1 ≥ 1%: 8.4 (6.9–12.4), 11.8 (7.1–27.4), and 5.7 (4.4–8.7) mo and for all randomized pts: 8.2 (6.9–9.7), 11.1 (8.3–14.0), and 7.1 (5.7–8.2) mo, respectively. No new safety signals were identified (Table). Conclusions: NIVO plus chemo and NIVO plus IPI both demonstrated superior OS vs chemo, along with durable objective responses and acceptable safety, in pts with advanced ESCC, and each represents a potential new 1L treatment option. Clinical trial information: NCT03143153. [Table: see text]

Addition of Aflibercept to Fluorouracil, Leucovorin, and Irinotecan Improves Survival in a Phase III Randomized Trial in Patients With Metastatic Colorectal Cancer Previously Treated With an Oxaliplatin-Based Regimen

2012 ◽  
Vol 30 (28) ◽  
pp. 3499-3506 ◽  
Author(s):  
Eric Van Cutsem ◽  
Josep Tabernero ◽  
Radek Lakomy ◽  
Hans Prenen ◽  
Jana Prausová ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
Growth Factor ◽  
Metastatic Colorectal Cancer ◽  
Growth Factor Receptor ◽  
Progression Free Survival ◽  
The United States ◽  
Phase Iii ◽  
Survival Times ◽  
Previously Treated

Purpose Treatment for metastatic colorectal cancer (mCRC) commonly involves a fluoropyrimidine-based chemotherapy regimen such as infusional fluorouracil, leucovorin, and irinotecan (FOLFIRI) or fluorouracil, leucovorin, and oxaliplatin, often combined with bevacizumab or an epidermal growth factor receptor monoclonal antibody. We studied the effect of adding the novel antiangiogenic agent aflibercept (also known as ziv-aflibercept in the United States) to FOLFIRI in patients with mCRC previously treated with oxaliplatin, including patients who received prior bevacizumab. Patients and Methods Patients were randomly assigned to receive aflibercept (4 mg/kg intravenously; 612 patients) or placebo (614 patients) every 2 weeks in combination with FOLFIRI. Treatment was administered until disease progression or unacceptable toxicity. The primary end point was overall survival. Results Adding aflibercept to FOLFIRI significantly improved overall survival relative to placebo plus FOLFIRI (hazard ratio [HR], 0.817; 95.34% CI, 0.713 to 0.937; P = .0032) with median survival times of 13.50 versus 12.06 months, respectively. Aflibercept also significantly improved progression-free survival (PFS; HR, 0.758; 95% CI, 0.661 to 0.869; P < .0001), with median PFS times of 6.90 versus 4.67 months, respectively. The effects on overall survival and PFS exhibited a consistent trend across prespecified subgroup analyses, including bevacizumab pretreated patients. Response rate was 19.8% (95% CI, 16.4% to 23.2%) with aflibercept plus FOLFIRI compared with 11.1% (95% CI, 8.5% to 13.8%) with placebo plus FOLFIRI (P = .0001). Adverse effects reported with aflibercept combined with FOLFIRI included the characteristic anti–vascular endothelial growth factor effects and also reflected an increased incidence of some chemotherapy-related toxicities. Conclusion Aflibercept in combination with FOLFIRI conferred a statistically significant survival benefit over FOLFIRI combined with placebo in patients with mCRC previously treated with oxaliplatin.

CanStem303C trial: A phase III study of napabucasin (BBI-608) in combination with 5-fluorouracil (5-FU), leucovorin, irinotecan (FOLFIRI) in adult patients with previously treated metastatic colorectal cancer (mCRC).

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. TPS3619-TPS3619 ◽  
Author(s):  
Axel Grothey ◽  
Manish A. Shah ◽  
Takayuki Yoshino ◽  
Eric Van Cutsem ◽  
Julien Taieb ◽  
...  
Keyword(s):  
Stem Cells ◽  
Cancer Stem Cells ◽  
Progression Free Survival ◽  
Tumor Location ◽  
Phase Iii ◽  
Secondary Endpoints ◽  
Phase Iii Study ◽  
Study Population ◽  
Previously Treated ◽  
Line Of Therapy

TPS3619 Background: Cancer stem cells are considered to be fundamentally important for resistance to therapy, recurrence and metastasis. Napabucasin is a first-in-class cancer stemness inhibitor in development identified by its ability to inhibit STAT3-driven gene transcription and spherogenesis of cancer stem cells (Li et al, PNAS 112(6):1839, 2015). Preclinically, napabucasin sensitizes cancer cells to chemotherapeutics, including 5-FU and irinotecan. Encouraging anticancer activity in advanced CRC was observed in a phase Ib/II (Bendell et al, GI ASCO 2017) study of 63 pts with disease control rate (DCR) of 93% (28/30) and overall response rate (ORR) of 33% (10/30) in FOLFIRI-naïve pts who have had an on-study RECIST evaluation. On the basis of these data, a phase III trial is being conducted in North America, Europe, Australia, and Asia. Methods: This study (ClinicalTrials.gov NCT02753127) will assess the efficacy of napabucasin+FOLFIRI vs FOLFIRI in pts with mCRC (n = 1250). Addition of bevacizumab (bev) is permissible per investigator choice. Pts must have failed 1 prior line of therapy with oxaliplatin and a fluoropyrimidine +/- bev for metastatic disease. Pts are randomized 1:1 to receive napabucasin 240 mg PO BID plus FOLFIRI bi-weekly, or FOLFIRI bi-weekly (bev may be added to FOLFIRI by investigator choice) and stratified by geography, time to progression on 1st-line therapy, RAS mutation status, bev as part of study treatment and primary tumor location. Treatment will continue until disease progression, or another discontinuation criterion. Primary endpoint is overall survival (OS) in the general study population (ITT) (HR 0.80 for OS improvement from 12.54 to 15.68 months); secondary endpoints include OS in the biomarker positive (biomarker+) population, progression free survival (PFS) in the ITT population, PFS in biomarker+ population, ORR and DCR in the ITT and in biomarker+ populations, safety and quality of life. Also, blood and tumor archival tissue will be assessed for PK and biomarker analyses. Global enrollment is underway. Clinical trial information: NCT02753127.

The efficacy and safety of sunitinib in patients with advanced well-differentiated pancreatic neuroendocrine tumors.

2017 ◽  
Vol 35 (4_suppl) ◽  
pp. 380-380 ◽  
Author(s):  
Eric Raymond ◽  
Matthew H. Kulke ◽  
Shukui Qin ◽  
Michael Schenker ◽  
Antonio Cubillo ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Neuroendocrine Tumors ◽  
Phase Iii ◽  
Pancreatic Neuroendocrine Tumors ◽  
Pivotal Phase ◽  
Treatment Naïve ◽  
Phase Iii Study ◽  
Previously Treated Patients ◽  
Previously Treated ◽  
Well Differentiated

380 Background: Sunitinib was approved by the FDA in 2011 for treatment of progressive, well-differentiated, advanced pancreatic neuroendocrine tumors (pNETs) based on a pivotal phase III study (NCT00428597) that showed a significant increase in progression-free survival (PFS) over placebo following early study termination. Subsequently, the FDA requested a post-approval study to support these findings. Methods: In this open-label, phase IV clinical trial (NCT01525550), patients with progressive, well-differentiated, unresectable advanced/metastatic pNETs received continuous sunitinib 37.5 mg once daily. Eligibility criteria were similar to the phase III study. Primary endpoint was investigator-assessed PFS per RECIST 1.0. This study is ongoing. Results: Sixty one treatment-naïve and 45 previously treated patients with progressive pNETs were treated with sunitinib: mean age, 54.6 years; males, 59.4%; white, 63.2%; ECOG PS 0, 65.1% or PS 1, 34.0%; and prior somatostatin analog, 48.1% (treatment-naïve, 39.3%; previously treated, 60.0%). At the data cutoff date, 82 (77%) patients discontinued treatment, mainly due to disease progression (46%). Median duration of treatment was ~11.9 months. Investigator-assessed median PFS (mPFS) was 13.2 months (95% CI, 10.9–16.7) in the overall population, with comparable mPFS in treatment-naïve and previously treated patients (13.2 vs 13.0 months). mPFS per independent radiologic review was 11.1 months (95% CI, 7.4–16.6). Objective response rate (ORR) per RECIST was 24.5%: 21.3% in treatment-naïve and 28.9% in previously treated patients. Median overall survival, although not yet mature, was 37.8 months. Treatment-emergent, all-causality adverse events (AEs) reported by ≥ 20% of all patients included neutropenia, diarrhea, leukopenia, fatigue, hand–foot syndrome, hypertension, abdominal pain, dysgeusia, and nausea. Most common grade 3/4 AEs were neutropenia (22%) and diarrhea (9%). Conclusions: The mPFS of 13.2 months and ORR of 24.5% observed in this study support the outcomes of the pivotal phase III study of sunitinib in pNETs and confirm its activity in this setting. AEs were consistent with known safety profile of sunitinib. Clinical trial information: NCT01525550.

A phase III randomized study of nivolumab plus ipilimumab versus nivolumab for previously treated patients with stage IV squamous cell lung cancer and no matching biomarker (Lung-MAP Sub-Study S1400I, NCT02785952).

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 9014-9014 ◽  
Author(s):  
Lyudmila Bazhenova ◽  
Mary Weber Redman ◽  
Scott N. Gettinger ◽  
Fred R. Hirsch ◽  
Philip C. Mack ◽  
...  
Keyword(s):  
Interim Analysis ◽  
Randomized Study ◽  
Stage Iv ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Grade 5 ◽  
Secondary Endpoints ◽  
Previously Treated Patients ◽  
Previously Treated ◽  
Grade 3

9014 Background: Lung-MAP is a master protocol for patients (pts) with stage IV previously treated SqNSCLC. S1400I enrolled pts who were not eligible for a biomarker-matched sub-study. Methods: S1400I is phase III randomized trial for immunotherapy-naïve patients with ECOG 0-1 not selected by PD-L1 expression. Pts were assigned 1:1 to nivolumab and ipilimumab (N+I) vs nivolumab (N). N was given at 3 mg/kg q 2w, I was given at 1 mg/kg q 6w. The primary endpoint was overall survival (OS). Secondary endpoints: investigator-assessed progression-free survival (IA-PFS), response by RECIST 1.1, and toxicity. Results: From December 18, 2015 to April 23, 2018, 275 pts enrolled and 252 determined eligible (125 N+I and 127 N). The study was closed for futility at an interim analysis. Baseline characteristics were similar across arms. mOS was 10.0 m (8.0-12.8) and 11.0 m (8.2-13.5) for N+I and N. HR 0.97 (0.71-1.31), p 0.82. mPFS was 3.8 m (2.3-4.2) and 2.9 m (1.8-3.9) for N+I and N. HR 0.84 (0.64-1.09), p 0.19. Outcomes based on PD-L1 and TBM subsets are shown in table. Response rates were 18% (12-25%) and 17% (11-24%) for N+ I and N. Median follow up for patients still alive was 17.4 m. Grade ≥3 treatment-related AEs occurred in 48(39%) of pts on N+I vs 38(31%) on N. irAE reported in 39% of pts on N+I and 34% of patients on N. Drug-related AEs led to discontinuation in 25% and 16% of pts on N+I and N. There were 5 grade 5 AE in N+I arm and 1 in N arm. Conclusions: S1400I failed to show improvement in outcomes with N+I. Study was closed for futility at interim analysis. Toxicities were not different between two arms. Clinical trial information: 02785952. [Table: see text]

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