Defects in DNA repair genes and long-term survival in cisplatin-based neoadjuvant chemotherapy for muscle invasive bladder cancer (MIBC).

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 4536-4536
Author(s):  
Benjamin Miron ◽  
Eric A. Ross ◽  
Fern Anari ◽  
John O'Neill ◽  
Jean H. Hoffman-Censits ◽  
...  
Keyword(s):  
Neoadjuvant Chemotherapy ◽  
Phase Ii ◽  
Pathologic Complete Response ◽  
Predictive Biomarkers ◽  
Complete Response ◽  
Phase Ii Trials ◽  
Two Phase ◽  
Term Survival

4536 Background: Although cisplatin-based neoadjuvant chemotherapy (NAC) has demonstrated an overall survival (OS) benefit in MIBC, only a subset of patients have pathologic complete response (pT0) at cystectomy. ATM, RB1 and FANCC mutations have shown correlation with pT0 to cisplatin-based NAC, as previously published. We now report updated OS and disease specific survival (DSS) from two phase II trials using these gene alterations as biomarkers. Methods: Patients with stage T2-T4 (N0 or N1) MIBC were enrolled in phase II trials of dose-dense NAC with MVAC (methotrexate, vinblastine, adriamycin, and cisplatin; NCT01031420) or GC (gemcitabine and cisplatin; NCT01611662). Patients were treated with NAC with plan for curative cystectomy. DNA from pretreatment tumor tissue was sequenced for coding exons of 287 cancer-related genes and analyzed for mutations. Survival in patients with one or more mutations in ATM, RB1, or FANCC genes was compared to those without mutations. Results: Of 58 pts treated, 38% (22/58 pts) had relevant mutations in the combined group of MVAC (13/34 pts) and GC (9/24 pts) trials. At a median follow-up of 56 months and minimum follow up of 16 months, patients with mutations had statistically significantly greater OS (p = 0.0043) and DSS (p = 0.0015). Median OS/DSS was not reached for patients with a mutation in any group. At 5 years post treatment, OS/DSS were greater in mutated vs non-mutated patients in all groups (see table). Conclusions: Long-term follow up reveals that previously reported improved responses to cisplatin-based NAC associated with mutations in ATM, RB1 and FANCC also confer a clinically meaningful and statistically significant survival benefit in these patients. These alterations may be useful as predictive biomarkers to allow clinicians to prioritize patients most likely to benefit from NAC prior to radical cystectomy. [Table: see text]

Long-term follow-up of a phase II randomized trial in advanced gastrointestinal stromal tumor (GIST) patients (pts) treated with imatinib mesylate

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 9528-9528 ◽  
Author(s):  
C. D. Blanke ◽  
G. D. Demetri ◽  
M. Von Mehren ◽  
M. C. Heinrich ◽  
B. L. Eisenberg ◽  
...  
Keyword(s):  
Phase Ii ◽  
Survival Rates ◽  
Complete Response ◽  
Tumor Control ◽  
Term Survival ◽  
Mutational Status ◽  
Exon 9 ◽  
Exon 11

9528 Background: Imatinib achieves tumor control in most pts with advanced GIST, but the durability of remissions has not been well described. We now present an updated long-term analysis of a randomized phase II trial first presented in 2001, with a median follow-up of 52 months. Methods: 147 pts with unresectable or metastatic malignant GIST were randomized to treatment with daily dosing of imatinib, 400 or 600 mg po. Results: Two pts (1%) achieved a complete response, 98 (67%) achieved a partial response (PR), and 23 (16%) exhibited stable disease (SD) as their best response. Median time-to-response was 13 weeks (95% CI; 12–23 weeks), but one quarter of pts responded after 23 weeks. No significant response differences were seen between the two dose levels tested. The median duration of response was 27 months, and median overall survival was 58 months. Pts with SD or PR had similar 4-year survival rates (64% versus 62%). KIT and/or PDGFRA mutational analyses were obtained in 87% of patients, and the mutational status was highly significant in predicting outcome. GISTs harboring KIT mutations in exon 11, exon 9, and with no detectable mutations in KIT or PDGFRA demonstrated PR rates of 87%, 48%, and 0%, respectively. The median survival for pts with exon 11 KIT mutations has not yet been reached, and it was 45 months for those with exon 9 mutations. Conclusions: While late progression can be seen in GIST pts treated with imatinib, the majority of pts derive benefit. Survival in those achieving SD parallels those with PRs. Late responses are often seen in pts with initial SD, and responses in general are of lasting duration. In particular, pts with KIT mutations in exon 11 (the most common exon affected) have very high response rates and favorable long term survival. [Table: see text]

Long-term follow-up of advanced gastric cancer patients who achieved a pathologic complete response with neoadjuvant chemotherapy.

2014 ◽  
Vol 32 (3_suppl) ◽  
pp. 133-133
Author(s):  
Haruhiko Cho ◽  
Takaki Yoshikawa
Keyword(s):  
Gastric Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Cancer Patients ◽  
Pathologic Complete Response ◽  
Complete Response ◽  
Pathological Response ◽  
Term Survival ◽  
Gastric Cancer Patients ◽  
The Impact

133 Background: Adjuvant chemotherapy (AC) after D2 gastrectomy has become a standard treatment for stage 2/3 gastric cancer in Japan and Korea; however, the results remain unsatisfactory due to insufficient risk reduction in patients with stage 3 disease and low compliance. Although the administration of neoadjuvant chemotherapy (NAC) is a promising approach associated with a high rate of compliance and a downstage effect, the long-term survival benefits of this modality are unclear. Moreover, the impact of the pathological response on survival has not been evaluated. Based on the hypothesis that the pathological response grade is associated with survival, we conducted a search for reports of a pathological complete response (pCR) obtained with NAC. Methods: A total of 27 gastric cancer patients who achieved a pCR following NAC therapy were identified using PubMed and the Japanese medical search engine “Ichu-shi,” with the search words “gastric cancer,” “NAC,” and “pCR.” A questionnaire regarding the patients’ prognoses was posted in 23 institutions in Japan in July 2013. Results: Answers regarding 22 patients were obtained from 20 institutions. The subjects included 13 males and nine females. The mean age was 67.5 years. Tumors with stage 3/4 (95.4%: 21/22) and a diffuse-type histology (61.9%: 13/21) were dominant. S1/CDDP was the most frequently selected NAC regimen. A total of 77.2% (17/22) of the patients required combined resection of adjacent organs, and all patients underwent R0 resection and D2 lymphadenectomy. At present, 86.3% (19/22) of the patients are alive without recurrence; none of the ten patients who received postoperative AC demonstrated any recurrence, while three of twelve patients who did not receive postoperative AC developed recurrence, and two patients died of the disease after surgery (at 71 months and nine months, respectively). The overall and recurrence-free survival rates at three/five years were 95.5%/85.1% and 90.9%/75.1%, respectively. Conclusions: Patients with gastric cancer who achieve a pCR with NAC are rare; however, their prognoses are excellent. It is therefore important to develop a NAC regimen focusing on a high pCR rate.

Prolonged Progression Free Survival Does Not Relate to Quality of Response to Treatment with Thalidomide in Patients with Relapsed Multiple Myeloma (MM).

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 2718-2718
Author(s):  
Hang Quach ◽  
Miles H. Prince ◽  
Linda Mileshkin ◽  
John F. Seymour ◽  
David Westerman ◽  
...  
Keyword(s):  
Phase Ii ◽  
Progression Free Survival ◽  
Complete Response ◽  
Response To Treatment ◽  
Phase Ii Trials ◽  
Term Survival ◽  
Free Survival ◽  
Multicentre Phase

Abstract Introduction: Quality of response to treatment in relapse/refractory MM, especially complete response (CR) or near complete response (nCR), has been reported to correlate with better PFS and OS in the past (Hussein MA, et al. Mayo Clin Proc2006;81:889–95). In this report, we provide an update on long-term survival from two multicentre phase II trials using thalidomide +/- IFNα2B (MM-thal) and combination celecoxib-thalidomide (Cel-thal) in relapsed or refractory MM, and identify predictors of progression-free survival (PFS) beyond 24 months (m). Method: In 1998 and 2001, two prospective multicentre phase-II trials in relapsed or refractory MM were performed to assess the efficacy of thalidomide +/- IFNα2B (MM-thal), and combination celecoxib-thalidomide (Cel-thal), respectively. Both studies were previously reported (Blood2003;102:69; Clin Can Res2005;11:5504). The analysis of progression free survival (PFS) has been updated using the Kaplan-Meier method. Baseline characteristics were compared between patients having PFS ≥ 24m and < 24m using fisher’s exact test or the Cochran-Armitage test, to identify predictors of long-term disease control. Result: Median follow up for MM-thal (n=75) and Cel-thal (n=66) trials were 73m and 47m respectively. Median PFS in the MM-thal trial was 5.5m, with estimated PFS of 9% at 3 years (95%, CI:5-18%), and 5% at 5 years (95%, CI:2-13%). In the Cel-thal trial, median PFS was 6.8m, with estimated PFS of 21% at 3 years (95% CI: 13-33%) and 16% at 5 years (95% CI:9-27%). Overall, 27 out of 141 patients (10 from MM-thal, 17 from Cel-thal) had PFS beyond 24m. The majority of these long term responders (70%) achieved only a PR as the best response to thalidomide-based treatment;15% achieved complete response (CR), and 15% had stable disease (SD). The most significant predictors for prolonged PFS of ≥24m was β2M ≥3mg/l (p<0.0005), stage ≥2 disease (p=0.001), and non-refractory disease to previous therapy (p=0.03). Bone marrow plasma cell infiltrate following thalidomide did not predict for outcome. Conclusion: Thalidomide, and in particular combination celecoxib-thalidomide has substantial activity in relapsed MM with prolonged PFS beyond 24m in approximately 19% of patients. The strongest predictor of prolonged PFS is β2M. The depth of response to thalidomide had little influence on predicting remission duration.

Long-term survival in patients with metastatic melanoma who received ipilimumab in four phase II trials.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 9053-9053 ◽  
Author(s):  
Celeste Lebbé ◽  
Jeffrey S. Weber ◽  
Michele Maio ◽  
Bart Neyns ◽  
Kaan Harmankaya ◽  
...  
Keyword(s):  
Metastatic Melanoma ◽  
Disease Progression ◽  
Phase Ii ◽  
Survival Data ◽  
Phase Iii ◽  
Phase Ii Trials ◽  
Term Survival ◽  
Long Term Survival

9053 Background: Ipilimumab (Ipi) has shown improved overall survival (OS) in two phase III trials of patients (pts) with metastatic melanoma (MM), with survival follow-up of >4 years in one trial. The present analyses provide survival follow-up of >5 years in four phase II trials of Ipi in MM. Methods: Pts with MM were enrolled in one of four phase II trials: (1) CA184-004, a biomarker study with Ipi at 3 or 10 mg/kg in treatment-naive (TN) and previously treated (PT) pts; (2) CA184-007, with Ipi at 10 mg/kg +/- prophylactic budesonide in TN and PT pts; (3) CA184-008, a single-arm study with Ipi at 10 mg/kg in PT pts; and (4) CA184-022, a dose-ranging study of Ipi at 0.3, 3, or 10 mg/kg in PT pts (crossover from lower dose groups to 10 mg/kg was allowed upon disease progression). Ipi was administered q3 wk x4 (induction), followed by maintenance (q12 wk from week 24) in eligible pts. Some pts were retreated with Ipi at 10 mg/kg upon disease progression. Along with survival data collected through March 2012 for studies 007, 008, and 022, we report updated 5-year OS data for study 004 collected through September 2012. Results: Five-year OS rates for TN and PT pts are reported in studies 007, 008, and 022, with combined analyses for TN and PT pts within each dose group in study 004 (Table). The results show that survival rates reach a plateau beginning at year 3. Conclusions: In pts who received Ipi at 3 or 10 mg/kg in phase II studies, regardless of prior treatment, a proportion (12.3–49.5%) remained alive 5 years after the start of treatment. These results demonstrate long-term survival with Ipi therapy in MM. An ongoing phase III trial will compare OS for Ipi at 3 vs 10 mg/kg in pts with MM. Clinical trial information: NCT00162123. [Table: see text]

Paclitaxel in the Neoadjuvant Treatment for Adeno carcinoma of the Distal Esophagus (AEG I). A Comparison of Two Phase II Trials with Long-Term Follow-Up

Onkologie ◽  
2008 ◽  
Vol 31 (7) ◽  
pp. 366-372 ◽  
Author(s):  
Franz G. Bader ◽  
Florian Lordick ◽  
Ulrich Fink ◽  
Karen Becker ◽  
Heinz H&ouml;fler ◽  
...  
Keyword(s):  
Phase Ii ◽  
Neoadjuvant Treatment ◽  
Distal Esophagus ◽  
Phase Ii Trials ◽  
Two Phase ◽  
Long Term Follow Up ◽  
Adeno Carcinoma

Long-term survival outcome of E1201: An Eastern Cooperative Oncology Group (ECOG) randomized phase II trial of neoadjuvant preoperative paclitaxel/cisplatin/radiotherapy (RT) or irinotecan/cisplatin/RT in endoscopy with ultrasound (EUS) staged esophageal adenocarcinoma.

2012 ◽  
Vol 30 (4_suppl) ◽  
pp. 69-69 ◽  
Author(s):  
Lawrence Kleinberg ◽  
Paul J. Catalano ◽  
Arlene A. Forastiere ◽  
Steven M. Keller ◽  
Pramila R. Anne ◽  
...  
Keyword(s):  
Esophageal Adenocarcinoma ◽  
Phase Ii ◽  
Performance Status ◽  
Pathologic Complete Response ◽  
Eastern Cooperative Oncology Group ◽  
Phase Ii Trials ◽  
Term Survival ◽  
Long Term Survival ◽  
C 30

69 Background: E1201 included operable esophageal adenocarcinoma, staged II-IVa by EUS and accrual ended Oct 2004. The primary endpoint was pathologic complete response (pCR), a surrogate endpoint generally associated with survival which did not meet criteria for further study of either arm. Long term survival results are now available. Stratification included clinical/EUS stage and ECOG performance status (PS). Methods: 81 eligible patients (pts) began treatment. Arm A was cisplatin (C) 30mg/m2 and irinotecan (I) 50 mg/m2 on days (d) 1, 8, 22, 29 of 45 Gy RT/5 weeks. Post-op therapy was C 30 mg/m2 and I 65 mg/m2 d 1, 8 q21 days x 3. Arm B therapy was C 30 mg/m2 and paclitaxel (P) 50 mg/m2 1 hour infusion d 1, 8, 15, 22, 29 with RT. Postoperative therapy was C 75 mg/m2 and P 175 mg/m2 day 1 q21 days x 3. Results: In Arm A, 26/39 have died. Median survival (S) is 35 m (months) and the 5, 6, and 7 year S was 46%, 39%, and 35%. In Arm B, 31/42 pts have died (one pt refused follow-up). Median S in arm B is 21 m. The 5, 6, and 7 year S was 27%, 27%, and 23%. Survival by EUS stage strata: For strata 1 (Stages T2N0M0 or T3N0M0), 14/20 have died. Median S is 37 m and 5 year S is 44%. In stage stratum 2 (Stages T1-3N1M0 or T1-3N0-1M1a), 43/61 have died. Median S is 24 m and 5 year S is 34%. For PS Strata: Patients with PS 0, had median S 35 m and 5 year S of 37% whereas for those with PS 1, the outcomes were 20m and 35%. Survival differences for the treatments and for these strata were not statistically significant. Conclusions: Long term survival is similar for both treatment arms and does not appear superior to results achieved with 5FU based regimens. The prognostic importance of the pretreatment strata was not confirmed. These data, along with the reported pCR (15% arm A; 17% arm B) and toxicity data (> =grade 3 during chemo/RT 68% arm A; 65% arm B), may have importance in aiding in the design and interpretation of ongoing and planned phase II trials adding novel agents or treatment approaches to backbones built on variations of these two regimens.

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