Primary results of NRG Oncology / NSABP B-43: Phase III trial comparing concurrent trastuzumab (T) and radiation therapy (RT) with RT alone for women with HER2-positive ductal carcinoma in situ (DCIS) after lumpectomy.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 508-508
Author(s):  
Melody A. Cobleigh ◽  
Stewart J. Anderson ◽  
Kalliopi P. Siziopikou ◽  
Douglas W Arthur ◽  
Thomas B. Julian ◽  
...  
Keyword(s):  
Ductal Carcinoma ◽  
Performance Status ◽  
Menopausal Status ◽  
Phase Iii ◽  
P Value ◽  
Primary Analysis ◽  
Her2 Positive ◽  
Ecog Performance Status ◽  
Intent To Treat

508 Background: Preclinical studies report that T can boost RT effectiveness. The primary aim of this trial assessed the efficacy of concurrent T + RT vs RT alone in preventing recurrence of ipsilateral breast cancer, ipsilateral skin cancer, or ipsilateral DCIS (IBTR) in women with DCIS. Methods: Eligibility: Women ≥18 yrs, ECOG performance status 0 or 1, DCIS resected by lumpectomy, and clear margins. Whole-breast RT after randomization was with 25+ fractions or accelerated with 16-17 fractions. RT boost was allowed. Centralized HER2 testing and ER and/or PR were required before entry. Stratification was by menopausal status, adjuvant endocrine therapy plan, and nuclear grade. T was given at 8 mg/kg IV within 1 wk before and 5 days after RT began (Dose 1) and at 6 mg/kg IV 3 wks after Dose 1 (Dose 2). Definitive intent-to-treat primary analysis was to be conducted when either 163 IBTR events were recorded or when all accrued pts were on study for ≥5 yrs. Results: 2014 pts were randomized (11/9/08 to 12/8/14);1998 (99.2%) had follow-up information. Median follow-up time on 12/31/19 was 79.2 mos. 2001 pts had RT information, 1965 (98.2%) completed RT: 988 (98.3%) in the RT arm and 977 (98.1%) in the RT+T arm. 996 pts had T compliance information in the RT+T arm, 939 (94.3%) completed two doses of T, 25 (2.5%) had one dose of T, and 32 (3.2%) did not receive T. At primary definitive analysis, 114 IBTR events occurred: 63 in the RT arm and 51 in the RT+T arm (HR = 0.81 [95% CI: 0.56-1.17], p-value = 0.26). 38 were invasive: 18 in the RT arm and 20 in the RT+T arm (HR = 1.11 [95% CI: 0.59-2.10], p-value = 0.74). 76 were DCIS: 45 in the RT arm and 31 in the RT+T arm (HR = 0.68 [95% CI: 0.43-1.08], p-value = 0.10). Annual IBTR event rates were 0.99%/yr in the RT group and 0.80%/yr in the RT+T group. There were 288 events of any kind [iDFS-DCIS] (DFS): 155 in the RT arm and 133 in the RT+T arm (HR = 0.84 [95% CI: 0.66-1.05], p-value = 0.13) and 48 deaths: 26 in the RT arm and 22 in the RT+T arm (OS HR = 0.85 [95% CI: 0.48-1.51], p = 0.59). The study did not reach the 163 protocol-specified events, so the definitive analysis was triggered by all pts having been on study for ≥5 years. Conclusions: The addition of T to RT did not achieve the protocol objective of 36% reduction in the IBTR rate but did achieve a modest, statistically non-significant reduction of 19%. Support: U10-180868, -180822, UG1-189867; Genentech. The authors thank Elaina Harper and Marlon Jones for data management. Clinical trial information: NCT00769379 .

Comparison of Radiation With or Without Concurrent Trastuzumab for HER2-Positive Ductal Carcinoma In Situ Resected by Lumpectomy: A Phase III Clinical Trial

2021 ◽  
pp. JCO.20.02824
Author(s):  
Melody A. Cobleigh ◽  
Stewart J. Anderson ◽  
Kalliopi P. Siziopikou ◽  
Douglas W. Arthur ◽  
Rachel Rabinovitch ◽  
...  
Keyword(s):  
Ductal Carcinoma In Situ ◽  
Carcinoma In Situ ◽  
Ductal Carcinoma ◽  
Menopausal Status ◽  
Eastern Cooperative Oncology Group ◽  
Phase Iii ◽  
Her2 Status ◽  
P Value ◽  
Her2 Positive

PURPOSE Preclinical studies report that trastuzumab (T) can boost radiotherapy (RT) effectiveness. The primary aim of the B-43 trial was to assess the efficacy of RT alone vs concurrent RT plus T in preventing recurrence of ipsilateral breast cancer (IBTR) in women with ductal carcinoma in situ (DCIS). PATIENTS AND METHODS Eligibility: Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1, DCIS resected by lumpectomy, known estrogen receptor (ER) and/or progesterone receptor (PgR), and human epidermal growth factor receptor 2 (HER2) status by centralized testing. Whole-breast RT was given concurrently with T. Stratification was by menopausal status, adjuvant endocrine therapy plan, and nuclear grade. Definitive intent-to-treat primary analysis was to be conducted when either 163 IBTR events occurred or all accrued patients were on study ≥ 5 years. RESULTS There were 2,014 participants who were randomly assigned. Median follow-up time as of December 31, 2019, was 79.2 months. At primary definitive analysis, 114 IBTR events occurred: RT arm, 63 and RT plus T arm, 51 (hazard ratio [HR], 0.81; 95% CI, 0.56 to 1.17; P value = .26). There were 34 who were invasive: RT arm, 18 and RT plus T arm, 20 (HR, 1.11; 95% CI, 0.59 to 2.10; P value = .71). Seventy-six were DCIS: RT arm, 45 and RT plus T arm, 31 (HR, 0.68; 95% CI, 0.43 to 1.08; P value = .11). Annual IBTR event rates were: RT arm, 0.99%/y and RT plus T arm, 0.79%/y. The study did not reach the 163 protocol-specified events, so the definitive analysis was triggered by all patients having been on study for ≥ 5 years. CONCLUSION Addition of T to RT did not achieve the objective of 36% reduction in IBTR rate but did achieve a modest but statistically nonsignificant reduction of 19%. Nonetheless, this trial had negative results. Further exploration of RT plus T is needed in HER2-positive DCIS before its routine delivery in patients with DCIS resected by lumpectomy.

Randomized phase III study of adjuvant chemotherapy for high-risk, node-negative breast cancer (BC) comparing FAC with FAC followed by weekly paclitaxel: First efficacy analysis of the GEICAM/2003-02 trial.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 1001-1001 ◽  
Author(s):  
Miguel Martin ◽  
Ana Lluch ◽  
Amparo Ruiz ◽  
Manuel Ruiz Borrego ◽  
Agust Barnadas ◽  
...  
Keyword(s):  
High Risk ◽  
Menopausal Status ◽  
Dose Intensity ◽  
Drop Out ◽  
Phase Iii ◽  
Weekly Paclitaxel ◽  
P Value ◽  
Her2 Positive ◽  
Node Negative

1001 Background: Adjuvant weekly paclitaxel (wP) sequential to anthracyclines improves the outcome of operable node-positive BC patients (pts) [Sparano NEJM 2008, Martin BCRT 2009]; however, most BC pts are currently node-negative at diagnosis. The role of wP in these pts is not well established yet. Methods: Pts aged 18-70, with T1-T3/N0 operable BC and at least one high-risk St Gallen 1998 criteria (size >2 cm, hormone-receptor [HR] negative, grade 2/3, age <35 years,) were eligible. HER2+ pts were allowed, after 792 entered the trial, the study was amended to exclude them. Pts were stratified by site, menopausal status, nodal status diagnostic method (sentinel-node biopsy versus lymphadenectomy) and HR status and randomized to receive FAC x6 (500/50/500 mg/m2 every 3w) or FAC x4→wP x8 (paclitaxel 100 mg/m2 weekly). The primary endpoint was DFS. The trial was designed to detect an absolute 5-y DFS increase of 5% (80% FAC, 85% FAC→wP); a sample size of 1812 evaluable patients (906 per arm) was required to detect this difference (α=0.05, β= 80%). Assuming a drop-out rate of 6%, 1929 pts were required. The first analysis of DFS was planned when a median follow-up of 5 years was reached. Results: Between September 2003 and October 2008, 1925 pts (FAC 974, FAC→wP 951) were randomized. Patient characteristics were well balanced between arms, median age was 50, 73% of pts were HR positive and 9% HER2 positive. 97% of pts with FAC and 85% of pts with FAC→wP completed all treatment as planned. The median dose intensity was 98% with FACx6, 99% with FACx4 and 98% with wP. The most frequent grade 3-4 toxicities (>3% in either arm) with FAC vs FAC→wP were neutropenia (25% vs 22%) with 4% vs 3% of febrile neutropenia, fatigue (3% vs 8%), sensory neuropathy (0 vs 5%), and vomiting (4% in each arm). After a median follow-up of 5.3 years, the proportion of patients disease free is 93% and 90% with FAC→wP and FAC (HR for relapse 0.732, 95% CI: 0.542 to 0.990; log-rank p-value=0.0423). Conclusions: For pts with high-risk node-negative BC, adjuvant FAC→wP was associated with a small but significant improvement in DFS compared with FAC, with manageable toxicity.

Phase II study of the frontline combination of ipilimumab and temozolomide in patients with metastatic melanoma.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 8514-8514 ◽  
Author(s):  
Sapna Pradyuman Patel ◽  
Wen-Jen Hwu ◽  
Kevin B. Kim ◽  
Nicholas E. Papadopoulos ◽  
Patrick Hwu ◽  
...  
Keyword(s):  
Overall Survival ◽  
Metastatic Melanoma ◽  
Phase Ii ◽  
Cell Function ◽  
Performance Status ◽  
Phase Iii ◽  
Induction Phase ◽  
Ecog Performance Status ◽  
Two Phase

8514 Background: Ipilimumab (Ipi) alters the immune system balance by inhibiting the suppression of T-cell function. In two phase III trials, Ipi has shown an overall survival benefit alone and in combination with dacarbazine in previously treated and treatment-naïve patients (pts) with metastatic melanoma (MM), respectively. We performed a single-institution, phase II clinical trial of Ipi plus temozolomide (Tem) in pts with MM. Methods: Pts between the ages of 18 and 75 with previously untreated unresectable stage III or stage IV MM and an ECOG Performance Status of 0 to 1 were enrolled in a phase II trial of Ipi plus Tem. Induction phase consisted of Ipi 10mg/kg intravenous on Day 1 and oral Tem 200 mg/m2 on Days 1 – 4 every 3 weeks for 4 doses. Maintenance consisted of Ipi 10 mg/kg intravenous on Day 1 starting week 12 and repeated every 12 weeks and oral Tem 200 mg/m2 on Days 1 – 5 starting week 12 and repeated every 4 weeks until disease progression or unacceptable toxicity occurred. The primary endpoint was progression-free survival (PFS) rate at 6 months. Responses were evaluated using immune-related response criteria. Results: Sixty-four pts were enrolled and received at least one dose of study drug. All pts were included in the analysis. With a median follow-up of 8.5 months, the PFS rate at 6 months was 43%, exceeding the proposed rate of 30%, and the median PFS was 5.1 months. There were 10 (15.6%) confirmed complete responses and 8 (12.5%) confirmed partial responses. At the time of this analysis, median overall survival has not been reached. Immune-related adverse events (irAEs) were experienced by 88% of pts, most commonly pruritus (88%), rash (83%), diarrhea (56%), transaminitis (45%), and colitis (11%). Grade 3/4 irAEs seen in more than one patient were skin rash (11%), diarrhea (9%), pruritus (6%), and transaminitis (5%). Constipation occurred in 70% of pts and was the most common gastrointestinal (GI) toxicity. There were no GI perforations or deaths on study due to treatment. Conclusions: At a median follow-up of 8.5 months, the best overall response rate in this study is 28%. Ipi at 10 mg/kg in combination with Tem given in an induction followed by maintenance fashion is safe, well-tolerated, and efficacious in MM.

Randomized phase II trial of carboplatin combined with weekly paclitaxel (CP) and docetaxel alone (D) in elderly patients (pts) with advanced non-small cell lung cancer (NSCLC): NJLCG 0801.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 7565-7565
Author(s):  
Shunichi Sugawara ◽  
Makoto Maemondo ◽  
Toshiyuki Harada ◽  
Akira Inoue ◽  
Nobumichi Matsubara ◽  
...  
Keyword(s):  
Performance Status ◽  
Stage Iv ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Toxicity Profile ◽  
Ecog Performance Status ◽  
Loss To Follow Up ◽  
Lethal Arrhythmia ◽  
Grade 3

7565 Background: Standard first-line chemotherapy for elderly NSCLC pts has been considered as a monotherapy with vinorelbine or gemcitabine globally. However, we have demonstrated the high efficacy of CP for elderly pts in our previous trial (Ann Oncol 2010). Meanwhile, D has been considered as an alternative option for this population in Japan according to the result of WJTOG9904 (JCO 2006). Thus we compared the two regimens to select the proper candidate for future phase III trial. Methods: Eligible pts were aged 70 years or older with newly diagnosed stage IIIB/IV NSCLC; ECOG performance status 0-1; adequate organ function; written informed consent. Pts were randomized to receive carboplatin (AUC 6) on day 1 and paclitaxel (70mg/m2 on day 1, 8, and 15) every 4 weeks or D (60mg/m2 on day 1) every 3 weeks. The primary endpoint was overall response rate (ORR), and secondary endpoints were progression-free survival (PFS), overall survival, and toxicity profile. Assuming that ORR of 40% would be potential usefulness while ORR of 20% would be the lower limit of interest, 40 pts in each arm were required if expect 10% loss to follow up. Results: Between July 2006 and September 2010, 84 pts were enrolled and 41 pts in CP arm and 42 pts in D arm were eligible (median age, 76 years; 75% male; 72% stage IV). Median treatment cycle was 4 in each arm (CP, range 1-6; D, range 1-8). ORRs were 51% (95%CI: 36-66%) and 26% (95%CI: 12-39%) in the CP and D arm, respectively. With a median follow-up of 18.4 months, median PFS were 6.5 and 3.9 months in the CP and D arm, respectively (Logrank, P=0.0027). Grade 3 or severer toxicities were as follows: neutropenia (CP, 56% and D, 79%), anemia (CP, 15% and D, 7%), thrombocytopenia (CP, 10% and D, 0%), infection (CP, 20% and D, 25%). One treatment-related death due to neutropenia, pneumonia, and lethal arrhythmia occurred in D arm but none in CP arm. Conclusions: The platinum doublet CP achieved higher activity with an acceptable toxicity profile for elderly pts with advanced NSCLC compared to monotherapy with D. The superiority of CP to the monotherapy in this trial is consistent with results of recent IFCT-0501 trial (Lancet 2011).

FOLFOXIRI plus bevacizumab (bev) versus FOLFIRI plus bev as first-line treatment of metastatic colorectal cancer (mCRC): Updated survival results of the phase III TRIBE trial by the GONO group.

2015 ◽  
Vol 33 (3_suppl) ◽  
pp. 657-657 ◽  
Author(s):  
Chiara Cremolini ◽  
Fotios Loupakis ◽  
Gianluca Masi ◽  
Vittorina Zagonel ◽  
Francesca Bergamo ◽  
...  
Keyword(s):  
Treatment Effect ◽  
Primary Tumor ◽  
Response Rate ◽  
Performance Status ◽  
Survival Rates ◽  
Phase Iii ◽  
First Line ◽  
Ecog Performance Status ◽  
Term Survival

657 Background: The phase III TRIBE trial met its primary endpoint, by demonstrating that first-line FOLFOXIRI plus bev significantly prolongs PFS, as compared to FOLFIRI plus bev. Also RECIST response rate, early response rate and deepness of response were significantly increased. At the first statistical analysis, with a median follow-up of 32.2 months, OS results were considered preliminary. Methods: Between July 2008 and May 2011, 508 patients were randomized to either FOLFIRI plus bev (arm A, n=256) or FOLFOXIRI plus bev (arm B, n=252). Both treatments were administered for a maximum of 12 cycles followed by 5FU/bev until progression. Results: At a median follow-up of 48.1 months, 374 deaths were recorded (Arm A=200 vs. Arm B=174). Median OS for Arm B vs. Arm A was 29.8 vs. 25.8 months (HR=0.80, 95% CI, 0.65-0.98, p=0.030). Long-term survival rates are reported in Table 1. Treatment effect was consistent across all analyzed subgroups. Among clinical variables, ECOG performance status of 1 or 2, right-sided primary tumor, synchronous metastases, disease not confined to the liver, unresected primary tumor, high Kohne score negatively affected prognosis at univariate analyses. At an exploratory model accounting for these variables, adjusted HR for treatment effect on OS was 0.77 (95% CI, 0.61-0.96, p=0.020). Conclusions: FOLFOXIRI plus bev improves survival of mCRC patients, as compared to FOLFIRI plus bev. The estimated 5-years OS rate of patients treated with FOLFOXIRI plus bev was equal to 24.9%, with an absolute benefit of 12.5% compared to controls. FOLFOXIRI plus bev represents a valuable option for the upfront treatment of mCRC. Clinical trial information: NCT00719797. [Table: see text]

Updated results from the phase III ALTTO trial (BIG 2-06; NCCTG (Alliance) N063D) comparing one year of anti-HER2 therapy with lapatinib alone (L), trastuzumab alone (T), their sequence (T→L) or their combination (L+T) in the adjuvant treatment of HER2-positive early breast cancer.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 502-502 ◽  
Author(s):  
Alvaro Moreno-Aspitia ◽  
Eileen McCormick Holmes ◽  
Christian Jackisch ◽  
Evandro De Azambuja ◽  
Frances M. Boyle ◽  
...  
Keyword(s):  
Disease Free Survival ◽  
Distant Recurrence ◽  
Phase Iii ◽  
Primary Analysis ◽  
Her2 Positive ◽  
Time To Recurrence ◽  
Long Term Follow Up ◽  
One Year ◽  
Treatment Comparisons

502 Background: Pre-specified 5-year analyses of the phase III Adjuvant Lapatinib and/or Trastuzumab Treatment Optimisation (ALTTO) Trial defined in Amendments 11&12. Methods: From June 2007 to July 2011, 8381 patients (pts) were randomised from 946 sites in 44 countries to receive either L+T, T→L, L, or T. In 2011, due to futility the L arm was closed and is not included in this analysis. The primary end point is disease-free survival (DFS). Secondary objectives include treatment comparisons with respect to overall survival (OS), time to recurrence (TTR), time to distant recurrence (TDR), cardiac and overall safety and tolerability. Primary analysis results of the study were published in JCO 2015 34:1034-1042. This updated analysis occurs at a 6.9 yrs median follow up (MFU). Results: All patients have reached 5-years of follow-up. 705 DFS events for L+T vs T have been observed. HR for DFS was 0.86 (95% CI, 0.74-1.00; 6-yr DFS%=85% vs 82%) for L+T vs T and 0.93 (95% CI, 0.81-1.08; 6-yr DFS%=84% vs 82%) for T→L vs. T. The 6-year OS was 93%, 92%, and 91% for L+T, T→L, and T, respectively. HR for OS was 0.86 (95% CI, 0.70-1.06) for L+T vs. T and 0.88 (95% CI, 0.71-1.08) for T→L vs. T. DFS differences for L+T vs. T were slightly higher for the hormone-receptor(ER)-negative [HR 0.80 (95% CI, 0.64-1.00; 6-yr DFS%=84% vs. 80%)] and the sequential chemotherapy [HR 0.83 (95% CI, 0.69-1.00; 6-yr DFS%=83% vs.79%)] subgroups. There were no differences in sites of first DFS events according to treatment arm for CNS, loco-regional, or distant recurrences. There were more AEs related to study treatment (L+T 93% vs T 64%). The incidence of primary cardiac end points was low: 1% for L+T, 0.5% for T→L and 0.9% for T. Conclusions: The HRs for this updated analysis are similar to those from the Primary Analysis and the event rate remains lower than anticipated (705 vs 850 planned). Cardiac toxicity remains low. This analysis suggests that HER2+/ER- tumors may have a different biology than HER2+/ER+ and may benefit more from dual HER2 blockade. Long-term follow up continues. Clinical trial information: NCT00490139.

Phase III, randomized study of first-line trastuzumab emtansine (T-DM1) ± pertuzumab (P) vs. trastuzumab + taxane (HT) treatment of HER2-positive MBC: Final overall survival (OS) and safety from MARIANNE.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 1003-1003 ◽  
Author(s):  
Edith A. Perez ◽  
Carlos H. Barrios ◽  
Wolfgang Eiermann ◽  
Masakazu Toi ◽  
Young-Hyuck Im ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Advanced Breast Cancer ◽  
Locally Advanced ◽  
Advanced Breast ◽  
Phase Iii ◽  
First Line ◽  
Primary Analysis ◽  
Her2 Positive ◽  
Grade 3

1003 Background: In MARIANNE (NCT01120184), patients with HER2-positive advanced breast cancer were randomized to trastuzumab + docetaxel or paclitaxel (HT; n=365), T-DM1 + placebo (T-DM1; n=367), or T-DM1 + P (T-DM1 + P; n=363) as first-line therapy. In the primary analysis, T-DM1–based treatment exhibited noninferior, but not superior, progression-free survival relative to HT (Perez EA, et al. J Clin Oncol 2016). OS was similar between treatments in the first interim analysis. Here we report OS from the final descriptive analysis. Methods: Enrolled patients had centrally assessed HER2-positive (IHC3+ or ISH+) progressive/recurrent locally advanced breast cancer or previously untreated MBC with a ≥6-month interval since (neo)adjuvant treatment with taxanes or vinca alkaloids. Results: At the clinical cutoff date of May 15, 2016, median follow-up was 54 months and 512 patients had died. Median OS was 50.9, 53.7, and 51.8 months with HT, T-DM1, and T-DM1 + P, respectively (Table). A sensitivity analysis in which HT-treated patients who received T-DM1 and/or P after disease progression (n=85) were censored prior to treatment switch found similar results. There were numerically fewer grade ≥3 adverse events (AEs) with T-DM1. Conclusions: With this longer follow-up, the T-DM1 safety profile was consistent with the primary analysis and prior experience. While OS was similar across treatment arms, a median OS of 53.7 months and fewer grade ≥3 AEs (vs other arms) supports T-DM1 as an effective and tolerable alternative first-line treatment for HER2-positive MBC patients. Clinical trial information: NCT01120184. [Table: see text]

Overall survival (OS) analysis from PRIME: Randomized phase III study of panitumumab (pmab) with FOLFOX4 for first-line metastatic colorectal cancer (mCRC).

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 3620-3620 ◽  
Author(s):  
Jean-Yves Douillard ◽  
Salvatore Siena ◽  
Josep Tabernero ◽  
Ronald L. Burkes ◽  
Mario Edmundo Barugel ◽  
...  
Keyword(s):  
Performance Status ◽  
Objective Response ◽  
Progression Free Survival ◽  
Final Analysis ◽  
Phase Iii ◽  
First Line ◽  
Primary Analysis ◽  
Ecog Performance Status ◽  
Exon 2 ◽  
Kras Exon

3620 Background: The primary and final analyses of PRIME demonstrated that pmab + FOLFOX4 significantly improved progression-free survival (PFS) vs FOLFOX4 alone for first-line treatment of patients (pts) with wild-type (WT) KRAS exon 2 mCRC. Methods: Pts were randomized 1:1 to pmab 6.0 mg/kg every 2 weeks + FOLFOX4 or FOLFOX4 alone and had no prior chemotherapy for mCRC, ECOG performance status ≤ 2, and tumor tissue for biomarker testing. The primary endpoint was PFS by central assessment. Secondary endpoints included OS, objective response rate, and safety. KRAS exon 2 tumor status was determined by a blinded central lab prior to the primary analysis. This exploratory analysis of updated survival (>80% OS events) estimated the treatment effect of pmab + FOLFOX4 compared with FOLFOX4 alone on OS by KRAS exon 2 status. Previous analyses in pts with WT KRAS exon 2 tumor status reported OS with an event rate of 54% of pts in the primary analysis and 68% of pts in the final analysis. Results: 1183 pts were randomized and received treatment: 593 pts in the pmab + FOLFOX4 arm and 590 pts in the FOLFOX4 alone arm. The KRAS exon 2 ascertainment rate was 93%, consistent with the primary analysis. 535/656 pts (82%) with WT KRAS exon 2 mCRC had an OS event at the time of this analysis. Results are shown (Table). Conclusions: In this updated analysis, an improvement in OS was observed in pts with WT KRAS exon 2 mCRC treated with pmab + FOLFOX4 vs FOLFOX4 alone (p = 0.03). Median OS was reduced in pts with mutant (MT) KRAS mCRC (p = 0.16) and is consistent with previous analyses. Updated efficacy and safety results will be presented. KRAS testing is critical to select appropriate pts with mCRC for treatment with pmab. Clinical trial information: NCT00364013. [Table: see text]

R-CHOP with or without Radiotherapy in Non-Bulky Limited-Stage Diffuse Large B Cell Lymphoma (DLBCL): Preliminary Results of the Prospective Randomized Phase III 02-03 Trial from the Lysa/Goelams Group

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 393-393 ◽  
Author(s):  
Thierry Lamy ◽  
Gandhi Damaj ◽  
Emmanuel Gyan ◽  
Pierre Soubeyran ◽  
Krimo Bouabdallah ◽  
...  
Keyword(s):  
Fdg Pet ◽  
Tumor Regression ◽  
Performance Status ◽  
B Cell Lymphoma ◽  
Phase Iii ◽  
Ecog Performance Status ◽  
Limited Stage ◽  
End Of Treatment ◽  
The Impact

Abstract The benefit of radiotherapy (RT) following chemotherapy in limited-stage DLBCL remains controversial. Before the Rituximab era, 4 randomized trials have been reported with conflicting results (ECOG 1484 and SWOG 8736, GELA 93-1 and 93-4 studies). More recently, the German Unfolder study prematurely closed the R-CHOP without RT arm in bulky limited-stage DLBCL due to an excess of relapse. In 2005, we conducted a randomized trial in patients with non-bulky (defined by a tumor size <7cm) limited-stage DLBCL to evaluate the benefit of RT following R-CHOP. Patients were stratified according to the Miller modified IPI including LDH (normal vs elevated), ECOG performance status (0-1 vs 2-3), age (<60 vs >60 yrs), stage (I vs II). Patients with IPI=0 (no risk factor) and those with IPI≥1 (≥1risk factor) received 4 or 6 consecutive cycles of R-CHOP 14 respectively, followed or not by IFRT at 40 GY delivered 4 weeks after the last cycle of R-CHOP. All patients were evaluated by an FDG-PET at baseline, after 4 cycles of R-CHOP and at the end of treatment. For patients in partial response (defined by a tumor regression >50% but a persistent positive FDG-PET) after C4, 2 additional cycles of R-CHOP followed by RT (even if not initially allocated) were recommended. The primary objective was EFS at one year after the last randomization, and secondary objectives were the impact of interim FDG-PET on EFS and the toxicity of RT. From May 2005 to December 2013, 313 patients were randomized and 301 patients are currently evaluable. Median age was 56 yr (20-75). There were 181 males and 120 females: 106 patients (35%) were older than 60 yr. Most patients had normal LDH (82%), PS=0 (80%), and no B symptoms (96% of cases). Modified IPI score was as follows: IPI =0 (n=170), IPI=1 (n=113), IPI=2 (n=16), IPI=3 (n=2). Main tumor sites were cervical (n=159), Waldeyer’s ring and sinus (n=36), inguinal (n=29), axillary (n=25), mediastinum (n=21). Extra-nodal sites were observed in 121 patients (40%). One hundred and fifty patients were randomized in the R-CHOP arm and 151 in the R-CHOP + RT arm. After 4 cycles, 253 patients (84%) were in CR and 43 in PR (14%). Three patients had stable disease. Thirty-four patients (79%) out of the 43 partial responders received 2 additional cycles of R-CHOP followed by RT (including 12 patients not initially allocated to RT arm). At the end of treatment, CR and PR rate were 94% and 3%, respectively. Seven (4%) out of the 151 patients randomized in the RT arm declined radiation. With a median follow-up of 51 months (2-110), there were 20 relapses: 12 in the R-CHOP arm and 8 in the R-CHOP+RT arm (p=ns). Sixteen patients died. Causes of death were as follows: relapses (n=9), toxic (n=1), secondary malignancies (n=3), unknown (n=3). Median time of relapse was 21 months (2-110 months). EFS and OS are not statistically different between the two arms. In an intent to treat analysis, 5y-EFS is 87% n the R-CHOP arm versus 91% in the R-CHOP + RT arm (HR=0.55), p=0.13, and 5yr-OS is 90% in the R-CHOP arm versus 95% in the R-CHOP + RT arm (HR=0.60), p=0.32. For patients in complete response after the 4 cycles of R-CHOP (84% of the patients), 5yr-EFS is 89% in the R-CHOP arm versus 91% in the R-CHOP + RT arm (HR=0.59), p=0.24. In this prospective study, the results demonstrate that in non-bulky limited-stage DLBCL, R-CHOP alone (4 to 6 cycles) induces very high CR rate with a very good overall survival and a very low relapse rate. With the current follow-up, the addition of radiotherapy is not significantly superior to R-CHOP alone and should be reserved to the minority of patients who do not reach CR after R-CHOP. Disclosures Gyan: Roche: Research Funding.

Factors affecting survival in upfront metastatic breast carcinoma patients.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e11540-e11540
Author(s):  
Ummugul Uyeturk ◽  
Burcin Budakoglu ◽  
Ibrahim Turker ◽  
Kaan Helvaci ◽  
Ozlem Uysal Sonmez ◽  
...  
Keyword(s):  
Breast Carcinoma ◽  
Survival Data ◽  
Ductal Carcinoma ◽  
Performance Status ◽  
Menopausal Status ◽  
Metastatic Breast ◽  
Her2 Status ◽  
Her2 Positive ◽  
Factors Affecting ◽  
Metastatic Breast Carcinoma

e11540 Background: Metastatic breast cancer is a heterogenous disease. There are several subgroups according to pathological, biological and molecular behaviours of the tumor. Recurrent metastatic breast carcinoma (RMBC) and upfront metastatic breast carcinoma (UMBC) may differ according to clinical and prognostic characteristics. Intrinsic genetic heterogeneity may be responsible for these differences. To date, little is known about the clinical features and outcome of patients with UMBC. Methods: Patients were considered to have UMBC if patients were admitted to the clinics with stage IV disease. Patients were considered to have RMBC if metastases had developed during followup for localized breast carcinoma. Between September 2007 and May 2011, 102 of 2478 (4.1%) UMBC patients who was admitted to Department of Medical Oncology Clinic, was included in this retrospective trial. Patients’ characteristics, treatment schedules and survival data were evaluated. Results: All patients were female. Median age was 50.0 (range: 26-90). More than half of patients (58.8%) were postmenopausal. Frequent histological type was invasive ductal carcinoma (89.2%). Most of the patients had grade 3 (57.8%) tumor. Hormone receptor (HR) and HER2 positivity were76.5% and 42.2%, respectively. Metastatic sites were visceral, isolated bone-soft tissue and combination in 20%, 42% and 37%, respectively. Most of visceral metastatic patients were HR negative and HER2 positive. Median PFS and OS were 30 and 66 months, respectively. Both PFS and OS were affected from HR status, HER2 status, sites of metastatic disease and chemotherapy (log-rank p=0.006, 0.04, 0.02, 0.004, 0.03 and log-rank p= 0.04, 0.04, 0.01, 0.03, 0.01 respectively). Both PFS and OS were not affected by age, menopausal status, performance status, histology and grade of the tumor. OS were longest in patients group who received chemotherapy (76 months) and shortest in patients group who received chemotherapy and targeted therapy combinations (23 months). Conclusions: Factors affecting survival were comparable to previous studies in UMBC patient population similiar to results RMBC studies. This finding should be confirmed with prospective trials in larger study populations.

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