Topotecan plus carboplatin versus standard therapy with paclitaxel plus carboplatin (PC) or gemcitabin plus carboplatin (GC) or carboplatin plus pegylated doxorubicin (PLDC): A randomized phase III trial of the NOGGO-AGO-Germany-AGO Austria and GEICO-GCIG intergroup study (HECTOR).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 5031-5031 ◽  
Author(s):  
Jalid Sehouli ◽  
Werner Meier ◽  
Pauline Wimberger ◽  
Radoslav Chekerov ◽  
Antje Belau ◽  
...  
Keyword(s):  
Standard Therapy ◽  
Progression Free Survival ◽  
Median Number ◽  
Phase Iii ◽  
Phase Iii Trial ◽  
Platinum Sensitive ◽  
Best Response ◽  
Phase Iii Study ◽  
Number Of Cycles

5031 Background: We present the efficacy data from a phase III study of topotecan (T) plus carboplatin (C) versus standard therapy with paclitaxel plus carboplatin (PC) or gemcitabine plus carboplatin (GC) or carboplatin plus pegylated doxorubicin (PLDC). Methods: From 02/07 to 12/09, 590 pts were screened and 550 pts were randomized to either T (0.75mg/m²/d1-3/q21d) + C (AUC 5/d1/q21d) or to standard therapy with CP or GC or PLDC based on patient preference. Progression free survival at 1 year was defined as primary endpoint. Results: Median number of cycles was 6 (range 0-9) in both arms. Most patients preferred GC (78%) in the standard therapy arm.. Best Response (CR+PR) was 73.1% (95%CI) and 75.1% (95%CI) for the CA. Median follow-up was 18 (0-52) months for TC and 20 (0-48) months for standard therapy. TC failed to show any advantage regarding 1-yr.-PFS or OAS. Conclusions: The combination of topotecan plus carboplatin failed to improve PFS or OAS in platinum sensitive relapsed ovarian cancer. In addition, carboplatin plus gemcitabine was well tolerated with lower rates of severe and long-lasting (neuropathy) toxicities compared to paclitaxel-carboplatin. [Table: see text]

Chemotherapy plus radiotherapy (CT-RT) versus RT alone for patients with anaplastic oligodendroglioma: Long-term results of the RTOG 9402 phase III study.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 2008b-2008b ◽  
Author(s):  
J. Gregory Cairncross ◽  
Meihua Wang ◽  
Edward G. Shaw ◽  
Robert B. Jenkins ◽  
Bernd W. Scheithauer ◽  
...  
Keyword(s):  
Combined Therapy ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Long Term Results ◽  
Phase Iii Trial ◽  
Free Survival ◽  
Entire Cohort ◽  
Phase Iii Study

2008b Background: Anaplastic oligodendrogliomas, pure (AO) and mixed (AOA), are chemosensitive tumors, especially if co-deleted for chromosomes 1p and 19q, but whether addition of CT to RT prolongs overall survival (OS), is unknown. Methods: In the RTOG 9402 Phase III trial, patients (pts) with AO/AOA were randomly assigned to PCV [procarbazine, CCNU (lomustine) and vincristine] followed by immediate RT vs. immediate RT alone. Early analysis showed no OS benefit for the PCV+RT group but combined therapy was associated with a longer progression-free survival (PFS). It also showed that the finding of 1p/19q co-deletion was associated with a longer OS independent of treatment. The current analysis has a median follow up of 11.3 years (yrs). Results: Two hundred ninety-one patients were randomized, 148 to PCV+RT and 143 to RT. PCV+RT was associated with longer PFS [2.5 vs. 1.7 yrs, hazard ratio (HR) 0.68, 95% confidence interval (CI) (0.53, 0.88), P = 0.003] and the 1p/19q co-deletion with a longer Median Survival Time (MST) [8.7 vs. 2.7 yrs, HR 0.41, 95% CI (0.30, 0.55), P < 0.001]. For the entire cohort, there was no difference in MST by treatment [4.6 yrs for PCV+RT vs. 4.7 yrs for RT, HR 0.79, 95% CI (0.60, 1.04), P = 0.1]. However, patients with 1p/19q co-deleted tumors lived much longer after PCV+RT (n = 59) than after RT (n = 67) [14.7 vs. 7.3 yrs, HR 0.59, 95% CI (0.37, 0.95), P = 0.03]. There was no difference in MST by treatment in pts without the 1p/19q co-deletion [n=137; 2.6 vs. 2.7 yrs, HR 0.85, 95% CI (0.58, 1.23), P = 0.39]. Re-operation rates upon progression were similar between treatment arms in co-deleted pts (43%, PCV+RT vs. 54%, RT) but salvage CT rates were higher in the RT arm [57% vs. 81% (P = 0.04)]. Conclusions: PCV followed by immediate RT was a highly effective therapy for patients with 1p/19q co-deleted AO/AOA. In this setting, 1p/19q co-deletion was both prognostic and predictive, and the early PFS benefit in co-deleted cases was a harbinger of their longer OS. [This work was supported by RTOG grants U10 CA21661 and U10 CA32115, NCCTG grant U10 CA25224, ECOG grants CA17145 and CA21115, SWOG grant CA32102, and CCOP grant U10 CA37422 from the National Cancer Institute (NCI)]

Safety and effectiveness of vinflunine in patients with metastatic transitional cell carcinoma of the urothelial tract (TCCU) after failure to one cisplatin-based systemic therapy in clinical practice.

2014 ◽  
Vol 32 (4_suppl) ◽  
pp. 332-332
Author(s):  
Belen Gonzalez-Grajera ◽  
Javier Puente ◽  
Iciar Garcia Carbonero ◽  
Nicolas Mohedano ◽  
M. Pilar Lopez Criado ◽  
...  
Keyword(s):  
Clinical Practice ◽  
Progressive Disease ◽  
Objective Response ◽  
Transitional Cell ◽  
Progression Free Survival ◽  
Median Number ◽  
Phase Iii ◽  
Disease Site ◽  
Number Of Cycles

332 Background: Vinflunine (VFL) is the first agent to show a survival improvement for platinum-refractory patients (pts) with metastatic TCCU in a phase III clinical trial. After EMA approval in September 2009, ESMO (Bellmunt, 2011) and SOGUG (Castellano, 2012) guidelines recommend VFL as second-line therapy. Methods: This is a multicenter and retrospective study to describe the experience with VFL in Spain. Pts with histologically confirmed metastatic TCCU were treated with VFL (280-320mg/m2 every 3 weeks) until progression or unacceptable toxicity. Pts were evaluated according to institutional local follow-up program. Results: From April 2010 to June 2013, we registered 102 pts in fifteen Spanish centers. All patients are evaluable for safety and 98 for efficacy. Median age: 67years (range 45-83), ECOG 0/1/2 previous to VFL (pts%): 31/61/8. Bladder carcinoma was the primary disease site in 84 pts and 46 % of them received cisplatinum-based chemotherapy. Metastatic involvement was: lymph nodes 67.7%, lung 36.4%, bone 28.1%, and liver 21.6%. The median number of cycles of VFL was 4 (1-18). The objective response rate was 25.5% (CR in 2 pts and PR in 23 pts), stable disease in 42.9% and progressive disease in 31.6%. The median follow-up was 6.6 months (0.4 to 43): median progression-free survival 3.9 months (95% CI, 2.3 to 5.5), median time to progression 4.3 months (95% CI, 2.6 to 5.9) and median overall survival 10 months (95% CI, 7.3 to 12.8). At the time of the analysis, 79.4%pts had progressive disease after VFL and 64.7% died. Grade 3/4 adverse events included: nausea/vomiting 13.8% of pts, neutropenia 12.8%, constipation 5.9%, and abdominal pain 4.9%. No toxic death were reported. Conclusions: This retrospective analysis confirms the benefit of VFL in patients with TCCU after failure in a platinum-containing chemotherapy regimen. Results of the randomized trial are reproducible in Spanish Oncology Centers on a daily clinical practice and its toxicity profile results are acceptable and manageable.

Final results of the EORTC Intergroup randomized phase III study 40983 [EPOC] evaluating the benefit of peri-operative FOLFOX4 chemotherapy for patients with potentially resectable colorectal cancer liver metastases

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. LBA5-LBA5 ◽  
Author(s):  
B. Nordlinger ◽  
H. Sorbye ◽  
L. Collette ◽  
B. Glimelius ◽  
G. J. Poston ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Liver Metastases ◽  
Dose Intensity ◽  
Progression Free Survival ◽  
Median Number ◽  
Phase Iii ◽  
Colorectal Cancer Liver Metastases ◽  
Significance Level ◽  
Phase Iii Study

LBA5 Background: The 5-year survival after resection of colorectal cancer liver metastases is 30% but recurrence is common. This study evaluates the benefit of combining peri-operative chemotherapy and surgery for patients with initially resectable liver only metastases from colorectal cancer (LM). Methods: Between September 2000 and July 2004, 364 pts with up to 4 LM were randomized between peri-operative FOLFOX4 (oxaliplatin 85mg/m2 and LV5FU2), 6 cycles before and 6 cycles after surgery, (CT), and surgery alone (S). The primary endpoint was progression free survival (PFS) with the goal to increase median PFS by 40% (HR=0.71). Safety was a secondary endpoint (already reported at ASCO 2005). PFS results are reported at the 2-sided 0.0434 significance level (adjusting for one interim analysis). Results: Baseline characteristics were similar in both arms. Eleven of 182 pts were ineligible in each arm, mostly for more advanced disease. In the CT arm, a median of 6 pre-op cycles were delivered and 151 patients were resected. 115 pts (63%) received post-op CT, with a median number of 6 cycles and a relative dose intensity of 79% to 86%. In the S arm, 152 pts were resected. Due to the nature of the trial, evaluation of resectability (relevant for eligibility) was based on pre-op imaging, but 31/182 pts (CT arm) and 30/182 pt (S arm) could not undergo resection. There were 2 (S arm) and 1 (CT arm) deaths after surgery. At a median follow-up of 3.9 years, 254 PFS events were reported (240 in eligible pts) and the results are as shown in the table . Conclusions: Peri-operative FOLFOX4 chemotherapy improved PFS over surgery alone in patients whose metastases were actually resected. The benefit was slightly diluted when also pts considered resectable on imaging but eventually not resected were taken into account. FOLFOX4 given peri-operatively is safe and does not prevent the pts from undergoing surgery. [Table: see text] [Table: see text]

A randomized, phase III study of carboplatin and pegylated liposomal doxorubicin versus carboplatin and paclitaxel in relapsed platinum-sensitive ovarian cancer (OC): CALYPSO study of the Gynecologic Cancer Intergroup (GCIG)

2009 ◽  
Vol 27 (18_suppl) ◽  
pp. LBA5509-LBA5509 ◽  
Author(s):  
E. Pujade-Lauraine ◽  
S. Mahner ◽  
J. Kaern ◽  
V. Gebski ◽  
M. Heywood ◽  
...  
Keyword(s):  
Liposomal Doxorubicin ◽  
Gynecologic Cancer ◽  
Pegylated Liposomal Doxorubicin ◽  
Progression Free Survival ◽  
Final Analysis ◽  
Phase Iii ◽  
Platinum Sensitive ◽  
Secondary Endpoints ◽  
Phase Iii Study

LBA5509 Background: This multicenter phase III study was designed to compare efficacy and safety of carboplatin-pegylated liposomal doxorubicin (PLD) (C-D) and carboplatin-paclitaxel (C-P) in relapsed platinum-sensitive OC patients (pts). Methods: Pts with recurrent OC > 6 months after first-line or second-line platinum-based therapy who had been pretreated with a taxane were randomized by stratified blocks to either C-D [C AUC 5 IV + PLD 30 mg/m2 IV] d1 q4 wk, or C-P [C AUC 5 IV + P 175 mg/m2 IV] d1 q3 wk × ≥ 6 cycles. The primary endpoint was progression-free survival (PFS), with secondary endpoints of toxicity, QoL and survival. The non-inferiority design required 745 events with 90% power, 95% confidence interval (CI). Results: From 4/05 to 09/07, 976 pts were enrolled, 467 to C-D arm and 509 to C-P arm. Pt parameters were well balanced. 85% of C-D and 78% of C-P pts received ≥ 6 cycles. Median follow-up is 21mo. Overall survival is still too early to be reported (n=308 deaths). This is the final analysis for PFS and toxicity. Results are below. Conclusions: This trial, the largest in relapsed OC, showed significant superiority of PLD-carboplatin combination in terms of PFS. In addition, compared to paclitaxel-carboplatin, PLD-carboplatin was well tolerated with lower rates of severe and long-lasting (neuropathy) toxicities. [Table: see text] No significant financial relationships to disclose.

Phase III Trial of Infusional Fluorouracil, Leucovorin, Oxaliplatin, and Irinotecan (FOLFOXIRI) Compared With Infusional Fluorouracil, Leucovorin, and Irinotecan (FOLFIRI) As First-Line Treatment for Metastatic Colorectal Cancer: The Gruppo Oncologico Nord Ovest

2007 ◽  
Vol 25 (13) ◽  
pp. 1670-1676 ◽  
Author(s):  
Alfredo Falcone ◽  
Sergio Ricci ◽  
Isa Brunetti ◽  
Elisabetta Pfanner ◽  
Giacomo Allegrini ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Peripheral Neurotoxicity ◽  
Phase Iii Trial ◽  
Free Survival ◽  
Secondary Resection ◽  
Phase Iii Study ◽  
Grade 3

Purpose The Gruppo Oncologico Nord Ovest (GONO) conducted a phase III study comparing fluorouracil, leucovorin, oxaliplatin, and irinotecan (FOLFOXIRI [irinotecan 165 mg/m2 day 1, oxaliplatin 85 mg/m2 day 1, leucovorin 200 mg/m2 day 1, fluorouracil 3,200 mg/m2 48-hour continuous infusion starting on day 1, every 2 weeks]) with infusional fluorouracil, leucovorin, and irinotecan (FOLFIRI). Methods Selection criteria included unresectable metastatic colorectal cancer, age 18 to 75 years, and no prior chemotherapy for advanced disease. The primary end point was response rate (RR). Results A total of 244 patients were randomly assigned. An increase of grade 2 to 3 peripheral neurotoxicity (0% v 19%; P < .001), and grade 3 to 4 neutropenia (28% v 50%; P < .001) were observed in the FOLFOXIRI arm. The incidence of febrile neutropenia (3% v 5%) and grade 3 to 4 diarrhea (12% v 20%) were not significantly different. Responses, as assessed by investigators, were, for FOLFIRI and FOLFOXIRI, respectively, complete, 6% and 8%; and partial, 35% and 58%, (RR, 41% v 66%; P = .0002). RR confirmed by an external panel was 34% versus 60% (P < .0001). The R0 secondary resection rate of metastases was greater in the FOLFOXIRI arm (6% v 15%; P = .033, among all 244 patients; and 12% v 36%; P = .017 among patients with liver metastases only). Progression-free survival (PFS) and overall survival (OS) were both significantly improved in the FOLFOXIRI arm (median PFS, 6.9 v 9.8 months; hazard ratio [HR], 0.63; P = .0006; median OS, 16.7 v 22.6 months; HR, 0.70; P = .032). Conclusion The FOLFOXIRI regimen improves RR, PFS, and OS compared with FOLFIRI, with an increased, but manageable, toxicity in patients with metastatic colorectal cancer with favorable prognostic characteristics. Further studies of FOLFOXIRI in combination with targeted agents and in the neoadjuvant setting are warranted.

scholarly journals Final Results of the IELSG-19 Randomized Trial of Mucosa-Associated Lymphoid Tissue Lymphoma: Improved Event-Free and Progression-Free Survival With Rituximab Plus Chlorambucil Versus Either Chlorambucil or Rituximab Monotherapy

2017 ◽  
Vol 35 (17) ◽  
pp. 1905-1912 ◽  
Author(s):  
Emanuele Zucca ◽  
Annarita Conconi ◽  
Giovanni Martinelli ◽  
Reda Bouabdallah ◽  
Alessandra Tucci ◽  
...  
Keyword(s):  
Overall Survival ◽  
Randomized Trial ◽  
Lymphoid Tissue ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Free Survival ◽  
Final Sample ◽  
Phase Iii Study ◽  
To Receive

Purpose There is no consensus on the optimal systemic treatment of patients with extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue. The IELSG-19 phase III study, to our knowledge, was the first such study to address the question of first-line treatment in a randomized trial. Patients and Methods Eligible patients were initially randomly assigned (1:1 ratio) to receive either chlorambucil monotherapy (6 mg/m2/d orally on weeks 1 to 6, 9 to 10, 13 to 14, 17 to 18, and 21 to 22) or a combination of chlorambucil (same schedule as above) and rituximab (375 mg/m2 intravenously on day 1 of weeks 1, 2, 3, 4, 9, 13, 17, and 21). After the planned enrollment of 252 patients, the protocol was amended to continue with a three-arm design (1:1:6 ratio), with a new arm that included rituximab alone (same schedule as the combination arm) and with a final sample size of 454 patients. The main end point was event-free survival (EFS). Analysis of chlorambucil versus the combination arm was performed and reported separately before any analysis of the third arm. Results At a median follow-up of 7.4 years, addition of rituximab to chlorambucil led to significantly better EFS (hazard ratio, 0.54; 95% CI, 0.38 to 0.77). EFS at 5 years was 51% (95% CI, 42 to 60) with chlorambucil alone, 50% (95% CI, 42 to 59) with rituximab alone, and 68% (95% CI, 60 to 76) with the combination ( P = .0009). Progression-free survival was also significantly better with the combination ( P = .0119). Five-year overall survival was approximately 90% in each arm. All treatments were well tolerated. No unexpected toxicities were recorded. Conclusion Rituximab in combination with chlorambucil demonstrated superior efficacy in mucosa-associated lymphoid tissue lymphoma; however, improvements in EFS and progression-free survival did not translate into longer overall survival.

Continuous versus interruption of imatinib (IM) in responding patients with advanced GIST after three years of treatment: A prospective randomized phase III trial of the French Sarcoma Group

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 10005-10005 ◽  
Author(s):  
A. Le Cesne ◽  
I. Ray-Coquard ◽  
B. Bui ◽  
M. Rios ◽  
A. Adenis ◽  
...  
Keyword(s):  
Mutational Analysis ◽  
Progression Free Survival ◽  
Final Analysis ◽  
Phase Iii ◽  
Tumor Control ◽  
Phase Iii Trial ◽  
One Year ◽  
The Impact ◽  
Advanced Gist

10005 Background: IM the first-line targeted therapy for advanced GIST, must not be interrupted after one year (yr) in responding patients (pts) and has to be given continuously until disease progression (PD) or intolerance (Blay, Le Cesne et al, ASCO 2004 and 2005). The impact on progression free survival (PFS) of IM discontinuation in long lasting responding pts is unknown. Methods: This prospective national multicenter BFR14 study was initiated in June 2002. After 3 yrs of IM 400mg/day, pts free from progression were randomly offered to continue (C arm) or interrupt (I arm) IM, with the exception of pts initially randomized in the I arm after 1 yr of IM (32 pts). Pts allocated to the I arm could restart IM (same dose) in case of PD. Primary endpoint was PFS. Pts declining randomization proceed with IM. Results: As of december 2006, 286 pts were included in this trial and up to date, 35 non progressive pts at 3 yrs were randomized, 19 and 16 in the I anc C arm respectively. Pt characteristics were well balanced between the two arms. Nine progressions were reported after a median follow-up of 5.3 months (range 0–14) in this cohort of patients. IM reintroduction in the I arm after a re-progression allowed again a tumor control (OR or SD) in all evaluable pts so far. Conclusions: An increase in the rate of PD was observed in patients randomized after 3 years of IM. The final analysis will be performed after the randomization of 50 pts. Updated results including mutational analysis will be presented at the meeting. No significant financial relationships to disclose.

A randomized, controlled, double-blind phase III study (AVOREN) of bevacizumab/interferon-α2a vs placebo/interferon- α2a as first-line therapy in metastatic renal cell carcinoma

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 3-3 ◽  
Author(s):  
B. Escudier ◽  
P. Koralewski ◽  
A. Pluzanska ◽  
A. Ravaud ◽  
S. Bracarda ◽  
...  
Keyword(s):  
Progression Free Survival ◽  
Final Analysis ◽  
Phase Iii ◽  
First Line ◽  
Double Blind ◽  
Phase Iii Trial ◽  
First Line Therapy ◽  
Interferon Α2a ◽  
Phase Iii Study ◽  
Adequate Organ Function

3 Background: Bevacizumab (BEV) is a monoclonal antibody that inhibits tumor angiogenesis by targeting VEGF. In relapsed RCC, BEV improved time to progression compared with placebo (2.5 vs. 4.8 months). A phase III trial was conducted to evaluate the efficacy and safety of BEV in combination with interferon (IFN)-a2a as first-line treatment in metastatic (m) RCC. The final analysis of progression-free survival (PFS) and interim analysis of overall survival (OS) are presented. Methods: Nephrectomized patients with clear cell mRCC, KPS of =70%, no CNS metastases and adequate organ function received IFN- a2a (x3/week at a recommended dose of 9 MIU for up to 1 year) plus BEV (10mg/kg q2w) or placebo until disease progression. Tumor assessments were performed every 8 weeks until week 32 and 12 weekly thereafter. Patients were stratified according to country and Motzer score. Results: Between June 2004 and October 2006, 649 patients were randomized (641 treated) at 101 centers in 18 countries. The treatment arms were well balanced for prognostic factors. At the data cutoff, 505 progression events had occurred, 111 patients remained on treatment, 287 had discontinued (discontinuations due to AEs were 12% with IFN vs. 28% with IFN-a2a/BEV), and 251 died. BEV-related side effects were generally mild and consistent with previous observations. The addition of BEV to IFN-a2a significantly increased PFS (10.2 vs. 5.4 mo) (HR=0.63; p<0.0001) and objective tumor response rate (30.6% vs. 12.4%; p<0.0001). A trend toward improved OS was observed with the addition of BEV to IFN-a2a (p=0.0670). Conclusions: BEV improves PFS when combined with IFN-a2a in mRCC. No unexpected safety events were observed. [Table: see text] [Table: see text]

Randomized phase III trial of dose-dense methotrexate, vinblastine, doxorubicin, and cisplatin (dd-MVAC) or gemcitabine and cisplatin (GC) as perioperative chemotherapy for muscle invasive urothelial bladder cancer (MIUBC): Preliminary results of the GETUG/AFU V05 VESPER trial on toxicity and pathological responses.

2020 ◽  
Vol 38 (6_suppl) ◽  
pp. 437-437 ◽  
Author(s):  
Stephane Culine ◽  
Gwenaelle Gravis ◽  
Aude Flechon ◽  
Michel Soulie ◽  
Laurent Guy ◽  
...  
Keyword(s):  
Progression Free Survival ◽  
Median Number ◽  
Phase Iii ◽  
Perioperative Chemotherapy ◽  
Urothelial Bladder ◽  
Secondary Endpoints ◽  
Grade 3 ◽  
Muscle Invasive ◽  
Dose Dense ◽  
Number Of Cycles

437 Background: The optimal perioperative chemotherapy regimen for patients (pts) with MIUBC is not defined. Methods: Between February 2013 and February 2018, 494 pts were randomized in 28 French centres and received either 4 cycles of GC every 3 weeks or 6 cycles of dd-MVAC every 2 weeks before surgery (neoadjuvant group) or after surgery (adjuvant group). The primary endpoint was the progression-free survival at 3 years. Secondary endpoints included toxicity, pathological responses and overall survival. Results: In the neoadjuvant group, 218 pts received dd-MVAC and 219 pts GC. The median number of cycles was 6 (0-6) and 4 (1-4), respectively. 60% of pts received 6 cycles in the dd-MVAC arm, 84% received 4 cycles in the GC arm. 199 pts (91%) and 198 (90%) pts underwent surgery, respectively. Complete pathologic responses (ypT0pN0) were observed in 84 (42%) and 71 (36%) pts, respectively (p=0.02). An organ-confined status (<ypT3pN0) was obtained in 154 (77%) and 124 (63%) pts, respectively (p=0.002). In the adjuvant group (57 pts), the median number of cycles was 5 (1-6) and 4 (1-4), respectively. 40% of pts received 6 cycles in the dd-MVAC arm, 60% received 4 cycles in the GC arm. Most of CTCAE grade ≥ 3 toxicities concerned hematological toxicities. At least one of these where reported for 125 (50%) pts in the dd-MVAC group and 134 (54%) pts in the GC group (p=NS). Gastrointestinal (GI) grade ≥ 3 disorders were more frequently observed in the dd-MVAC arm (p<0.0001) as well as grade ≥ 3 asthenia (p<0.00001). Four deaths (3 in the dd-MVAC) occurred during chemotherapy. Conclusions: Complete pathological responses and organ-confined status were more frequently observed in the dd-MVAC arm. Toxicity was manageable with more severe asthenia and GI side effects in the dd-MVAC arm. Clinical trial information: 2012-000563-25.

scholarly journals Efficacy of Osimertinib Plus Bevacizumab In Glioblastoma Patients With Simultaneous EGFR Amplification And EGFRvIII Mutation

2021 ◽  
Author(s):  
Daniel Jaramillo-Velásquez ◽  
Andrés F. Cardona ◽  
Alejandro Ruiz-Patiño ◽  
Carolina Polo ◽  
Enrique Jiménez ◽  
...  
Keyword(s):  
Overall Response Rate ◽  
Kinase Inhibitors ◽  
Progression Free Survival ◽  
Median Number ◽  
Resistance Pattern ◽  
Free Survival ◽  
Egfr Amplification ◽  
Egfr Tyrosine Kinase Inhibitors ◽  
Number Of Cycles

Abstract Background: Amplification of EGFR and its active mutant EGFRvIII are common in glioblastoma (GB). While EGFR and EGFRvIII play critical roles in pathogenesis, targeted therapy with EGFR-tyrosine kinase inhibitors (TKIs) or antibodies has shown limited efficacy. To improve the likelihood of effectiveness, we targeted adult patients with recurrent GB enriched for simultaneous EGFR amplification and EGFRvIII mutation, with osimertinib/bevacizumab at doses described for non-small cell lung cancer (NSCLC). Methods: We retrospectively explored whether previously described EGFRvIII mutation in association with EGFR gene amplification could predict response to osimertinib/bevacizumab combination in a subset of 15 patients treated at recurrence. The resistance pattern in a subgroup of subjects is described using a commercial NGS panel in liquid biopsy.Results: There were ten males (66.7%), and the median patient’s age was 56 years (range 38-70 years). After their initial diagnosis, 12 patients underwent partial (26.7%) or total resection (53.3%). Subsequently, all cases received IMRT and concurrent and adjuvant temozolomide (TMZ; the median number of cycles 9, range 6-12). The median follow-up after recurrence was 17.1 months (95% CI 12.3-22.6). All patients received osimertinib/bevacizumab as a second-line intervention with a median progression-free survival (PFS) of 5.1 months (95% CI 2.8-7.3) and overall survival (OS) of 9.0 months (95% CI 3.9-14.0). The PFS6 was 46.7%, and the overall response rate (ORR) was 13.3%. After exposure to the osimertinib/bevacizumab combination, the main secondary alterations were MET amplification, STAT3, IGF1R, PTEN, and PDGFR.Conclusions: While the osimertinib/bevacizumab combination was marginally effective in most GB patients with simultaneous EGFR amplification plus EGFRvIII mutation, a subgroup experienced a long-lasting meaningful benefit. The findings of this brief cohort justify the continuation of the research in a clinical trial. The pattern of resistance after exposure to osimertinib/bevacizumab includes known mechanisms in the regulation of EGFR, findings that contribute to the understanding and targeting in a stepwise rational this pathway.

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