Concurrent platinum-based chemotherapy with intensity modulated radiation therapy (IMRT) for locally advanced squamous cell carcinoma of the head and neck (SCCHN): A retrospective single institution analysis

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 16511-16511
Author(s):  
N. F. Saba ◽  
J. Gaultney ◽  
S. Edelman ◽  
M. Tighiouart ◽  
L. W. Davis ◽  
...  
Keyword(s):  
Locally Advanced ◽  
Disease Free Survival ◽  
Nodal Status ◽  
Entire Cohort ◽  
Excellent Outcome ◽  
Stage Distribution ◽  
T Stage ◽  
Platinum Based Chemotherapy ◽  
N Stage

16511 Background: Randomized clinical and meta-analysis data support the use of concurrent chemoradiation for treatment of locally advanced (SCCHN). IMRT is increasingly being used in treating SCCHN. We present outcome data from Emory University Winship Cancer Institute (WCI) with concurrent platinum based chemotherapy and IMRT, and analyze results according to primary site and nodal status. Methods: Between February 2003, and November 2005, 87 patients with locally advanced SCCHN underwent concurrent IMRT and platinum based chemotherapy. A total of 62 patients were treated with Cisplatin 100 mg/m2 d1,21,43, while 19 were treated with paclitaxel and carboplatin weekly for 7 weeks. Five patients were treated with other platinum based regimens. Follow up was documented in all cases with a median of 520 days (range 107 - 1269 days). Results: Patients were distributed among primary sites as follows: Hypopharynx (HP) 7 (8.0%), Larynx (L) 11(12.4%), Nasopharynx (NP) 13 (14.6%), and Oropharynx (OP) 56 (63.0%). T stage distribution was: T1: 16 patients (18.0%); lesions more advanced than T1 (>T1): 68 (76.4%). N stage distribution was, N0 :16 patients (18.0%), N1: 8 (9.0 %),nodal stage N2a or higher: 61 (68.5%). Median age was 57 years (range 32–75), and 63 patients (71.0%) were male. The median overall survival (OS) and disease-free survival (DFS) post-therapy was not reached. The 3 year OS rate for the entire cohort was 86% (L 82%, NP 89 %, OP 86 % HP 80%). The 3 year DFS rate for the entire cohort was 74%, (L 85%, NP 60%, and OP 75%, HP 76%). There was no correlation between OS and T or N stage (p=0.143 and 0.44 respectively), or between DFS and T-stage (p=0.4). A significant correlation was found between DFS and N stage (p=0.008). Conclusion: With moderate follow up, this retrospective analysis reveals an excellent outcome for patients with locally advanced SCCHN treated with chemotherapy and IMRT concurrently, supporting concurrent therapy as the current standard of care. The significant correlation of DFS and nodal status suggests a possible greater impact future approaches such as induction therapy may have on patients with advanced nodal disease. No significant financial relationships to disclose.

scholarly journals IMRT in carcinoma cervix: Maximizing the gain and nipping the side effects: RGCI experience

2016 ◽  
Keyword(s):  
Acute Toxicity ◽  
Locally Advanced ◽  
Disease Free Survival ◽  
Complete Response ◽  
Concurrent Chemotherapy ◽  
Radiation Dermatitis ◽  
Carcinoma Cervix ◽  
Definitive Radiotherapy ◽  
Entire Cohort

Objective: To present a single institutional experience with acute toxicity, patterns of failure and survival in carcinoma cervix treated using definitive radiotherapy with IMRT technique. Methods: It is a retrospective analysis of 64 patients with carcinoma cervix treated with definitive chemoradiation (IMRT) from April 2011 to Jan 2013. Patients with squamous or adenocarcinoma histology and no metastasis, treated with definitive radiotherapy (IMRT) with or without concurrent chemotherapy were included. Acute toxicities were presented as proportions and kaplainmeier computation was done to calculate 3 years disease free survival (DFS) and 3 years overall survival (OS). Results: Median follow up was months for the entire cohort. Mean age was 55.9 years (SD 9.93). Majority of patients (92.8%) had locally advanced disease (FIGO II and III) and squamous cell carcinoma (96.9%). Mean dose to pelvis with IMRT was 49.75 Gy (SD 1.78) followed by ICRT, EBRT boost and implant in 79.7%, 17.2% and 3.1% respectively (as indicated). Response evaluation done at 3 months of treatment completion showed 83.6% complete response, 11.5% partial response and 4.9% progressive disease. During follow up 21.6% developed recurrence - 44.4% failed locally, 16.7% at para-aortic nodal region and 38.9% at distant sites. The 3 year DFS and OS was 70.8% and 60.3% respectively. Patients had tolerable acute toxicities. Incidences of grade ≥3 acute toxicity were 3.1% for anemia, 10.9% for neutropenia, 25% for thrombocytopenia, 1.5% for nausea, 0% for vomiting, 12% for GU and 12% for GI toxicities. Incidence of grade I, II and III radiation dermatitis were 38.89%, 27.78% and 22.2% respectively. None developed grade IV radiation dermatitis. Conclusion: IMRT for carcinoma cervix seems to provide improved outcomes and toxicity profile, although it should be compared with conventional radiotherapy in a well randomized control setting so as to have true and meaningful comparison.

Efficacy of cetuximab after immunotherapy (IO) in advanced cutaneous squamous cell carcinoma (CSCC).

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 9562-9562
Author(s):  
Julian Andres Marin-Acevedo ◽  
Bethany Withycombe ◽  
Youngchul Kim ◽  
Zeynep Eroglu ◽  
Joseph Markowitz ◽  
...  
Keyword(s):  
Locally Advanced ◽  
Acquired Resistance ◽  
Standard Of Care ◽  
Line Treatment ◽  
Second Line ◽  
Survival Times ◽  
Entire Cohort ◽  
Overall Response ◽  
Curative Radiotherapy

9562 Background: Anti-PD1 (aPD1) monotherapy with cemiplimab-rwlc or pembrolizumab is now considered standard of care for first-line management of advanced CSCC not amenable to surgery or curative radiotherapy. Previously chemotherapy or anti-EGFR agents were commonly used for these patients albeit with modest efficacy and limited duration of response. In prospective evaluation, the overall response rate (ORR) to cetuximab was 28% with disease control rate (DCR) of 69% at 6 weeks. The efficacy of second-line treatment following primary or acquired resistance to aPD1 therapy is not known. We investigated the activity of cetuximab in patients who progressed on previous IO therapy. Methods: We performed a single institution retrospective review from 9/28/18 (US approval date of cemiplimab-rwlc for CSCC) through 11/30/20 of patients with locally advanced or metastatic CSCC who received cetuximab after prior IO therapy. We identified patients who received cetuximab either immediately following IO therapy (cohort A) or as a subsequent line not immediately following IO therapy (cohort B). Primary endpoint was ORR with secondary endpoints of DCR, survival and toxicity. Median follow-up and survival times were calculated using the Kaplan-Meier method. Results: Thirteen patients, median age 72 years (62-82), all Caucasian, and 11 males (85%) were included in this study. Eleven pts received cetuximab immediately post-IO progression; two had additional intervening therapy post-IO before receiving cetuximab. Three patients received concurrent radiotherapy (palliative or definitive) with cetuximab. The ORR to cetuximab was 54% (7/13) including 1 complete and 6 partial responses. The cumulative 6-month DCR was 77%. All responses were observed in cohort A; both patients in cohort B had progressive disease as best response. Six of 7 initial responses are ongoing, including 3 in whom cetuximab was discontinued. At a median follow-up of 9.1 months, the median PFS has not been reached for the entire cohort. There were no unanticipated toxicities to cetuximab with rash (77%) and hypomagnesemia (54%) being the most common adverse events. Conclusions: In advanced CSCC, cetuximab used immediately after progression on aPD1 therapy yields notably higher and durable overall response than previously reported in the pre-IO therapy era. If validated in a larger dataset, this should be the preferred therapy for second-line treatment in advanced CSCC. Further exploration into the mechanism of this high efficacy of anti-EGFR therapy post aPD1 therapy is warranted.

scholarly journals Combination of CDX2 expression and T stage improves prognostic prediction of colorectal cancer

2019 ◽  
Vol 47 (5) ◽  
pp. 1829-1842 ◽  
Author(s):  
Weimin Xu ◽  
Yilian Zhu ◽  
Wei Shen ◽  
Wenjun Ding ◽  
Tingyu Wu ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
Disease Free Survival ◽  
Hazard Ratio ◽  
Free Survival ◽  
T Stage ◽  
Cdx2 Expression ◽  
Prognostic Prediction ◽  
Disease Free

Objective Prognostic prediction of colorectal cancer (CRC) remains challenging because of its heterogeneity. Aberrant expression of caudal-type homeobox transcription factor 2 (CDX2) is strongly correlated with the prognosis of CRC. Methods Tissue samples of patients with CRC who underwent surgery in Xinhua Hospital (Shanghai, China) from January 2010 to January 2013 were collected. CDX2 expression was semiquantitatively evaluated via immunohistochemistry. Results In total, 138 patients were enrolled in this study from a prospectively maintained institutional cancer database. The median follow-up duration was 57.5 months (interquartile range, 17.0–71.0 months). In the Cox proportional hazards model, low CDX2 expression combined with stage T4 CRC was significantly the worst prognostic factor for disease-free survival (hazard ratio = 7.020, 95% confidence interval = 3.922–12.564) and overall survival (hazard ratio = 5.176, 95% CI = 3.237–10.091). In the Kaplan–Meier survival analysis, patients with low CDX2 expression and stage T4 CRC showed significantly worse disease-free survival and overall survival than those with low CDX2 expression alone. Conclusion CDX2 expression combined with the T stage was more accurate for predicting the prognosis of CRC. Determining the prognosis of CRC using more than one variable is valuable in developing appropriate treatment and follow-up strategies.

Neoadjuvant chemotherapy (NACT) with prolonged high-dose (HD) doxorubicin (A) and cyclophosphamide (C) with G-CSF support in locally advanced breast cancer (LABC): Long-term follow-up data

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 11090-11090
Author(s):  
S. Altintas ◽  
M. T. Huizing ◽  
I. Spoormans ◽  
J. Van den Brande ◽  
P. Wilmes ◽  
...  
Keyword(s):  
Residual Disease ◽  
Locally Advanced ◽  
Disease Free Survival ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
High Dose ◽  
Axillary Lymph ◽  
Study Objective ◽  
Ventricular Ejection Fraction

11090 Background: NACT improves survival in LABC. The optimal regimen, dose and duration is still under study Objective: To determine the efficacy and safety of prolonged preoperative HD-AC plus G-CSF. Methods: LABC patients (pts) were treated with AC for 6 cycles (Cy): Cy 1: A 90 mg/m2, C 1000 mg/m2; Cy 2–3: A 82.5 mg/m2, C 875 mg/m2; Cy 4–6: A 75mg/m2, C 750 mg/m2) with prophylactic (peg)filgastrim q3wks. In case of cardiotoxicity or poor tumor response (TR) pts switched to Docetaxel (D) 100mg/m2 q3wks. Within 5 weeks after NACT, pts underwent mastectomy with axillary lymph node dissection followed by radiotherapy. In case of positive estrogen (ER) or progesteron receptor (PgR), hormonal treatment was given for 5 yrs. Toxicity was scored weekly (NCI-CTC 2), response every 3 wks (WHO). Kaplan-Meier analysis was performed to calculate disease free survival (DFS) and overall survival (OS). Results: Between 8/1997 and 10/2003 21 pts (median age 55 years, range 22–74) were enrolled. One pt had stage IIB, 6 stage IIIA, 14 stage IIIB disease (10 T4d). 10 tumors were ER+, 5 PgR+, none overexpressed Her-2/Neu. A total of 130 NACT Cy was given. 15 pts completed all 6 AC Cy, 6 switched to D because of a decrease in left ventricular ejection fraction (LVEF? >10%, n=2) or insufficient TR (n=4). Dose reduction of AC was needed in 1 pt (last Cy), dose delays in 4 pts. Nausea and vomiting were generally mild; grade 4 anorexia occured in one pt. Grade 4 leucopenia and neutropenia in 14 and 18 pts, respectively. Neutropenic fever requiring hospitalization occurred in 5 pts, thrombocytopenia grade 4 in 7 pts and grade 3 anemia in 3 pts. Two pts developed cardiomyopathy (9.5%) < 2 years after NACT. The overall TR rate (PR and CR) was 81%, clinical CR rate 14%, pathologic CR rate 10% and 14% had minimal residual disease. Three pts showed SD and only 1 pt had PD. The median follow up of all pts was 51 months (range 9–110), 5 yrs DFS 47%, OS 56%. 5 yrs DFS and OS for pT4d pts was 50% and 56%, respectively. Conclusions: NACT with HD-AC plus G-CSF for 6 Cy in this poor risk population is active and further supports the use of prolonged preoperative CT. The routine use of D after a restricted number of AC Cy may further improve results and decrease (cardio)toxicity. No significant financial relationships to disclose.

Cetuximab versus cisplatin concurrent with IMRT in locally advanced head and neck cancer (LAHNC)

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e17030-e17030 ◽  
Author(s):  
S. L. Galper ◽  
H. Deshpande ◽  
M. G. Rose ◽  
R. H. Decker
Keyword(s):  
Treatment Time ◽  
Randomized Study ◽  
Locally Advanced ◽  
Late Toxicity ◽  
Distant Metastases ◽  
Overall Treatment Time ◽  
Tumor Registry ◽  
Altered Fractionation ◽  
N Stage

e17030 Background: Concurrent chemoradiation of LAHNC with cetuximab or cisplatin improves survival. The purpose of this study is to compare cetuximab chemoradiation (ExRT) with cisplatin chemoradiation (ChRT) in patients treated with IMRT. Methods: Between January 2005 and August 2008, 24 patients with LAHNC were treated with definitive chemoradiation utilizing IMRT. ExRT was reserved for those whose age or comorbidities precluded ChRT. 15 patients were treated with ChRT and 9 patients were treated with ExRT. Patient charts and Tumor Registry data were reviewed for acute and late toxicity and for local/regional failure (LRF), distant metastases and death. Results: The ExRT cohort was significantly older (median age 71 vs 58, p=0.005) and had more larynx/hypopharynx primaries (44% vs 27%). The cohorts were otherwise balanced with respect to T- and N-stage. Median follow-up for the ExRT and ChRT cohorts was 11 and 12 months, respectively. Overall treatment time in compliant patients was lower in ExRT patients (46 vs 50 days, p=0.05), reflecting increased use of accelerated radiation fractionation (66% vs 40%). See Table for toxicity outcomes. There was a trend toward increased ≥G3 acute mucositis in the ExRT group (p=0.07). However, there was less weight loss (p=0.05). There were similar acute epidermitis and hospitalizations for malnutrition/hydration rates and a nonsignificant decrease in prolonged mucosal toxicity. 1 patient developed skin necrosis and another osteoradionecrosis in the ChRT group. 1-year freedom from LRF was 89% in the ChRT group vs 56% in the ExRT group (p=0.07). Overall survival (OS) at 1 year was 100% (ChRT) vs 88% (ExRT). Conclusions: ExRT showed a trend toward worse acute mucosal toxicity but not late toxicity despite increased rates of altered fractionation with a higher daily dose. ExRT was associated with worse LRC and OS. A randomized study would best compare outcomes and toxicity profiles. Until such analysis, cetuximab should be reserved for patients unable to tolerate ChRT. [Table: see text] No significant financial relationships to disclose.

Polymorphisms of thymidylate synthase as prognostic factor in rectal cancer.

2011 ◽  
Vol 29 (4_suppl) ◽  
pp. 433-433
Author(s):  
V. Arrazubi ◽  
J. Suarez ◽  
D. Guerrero ◽  
K. Cambra ◽  
M. L. Gomez Dorronsoro ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Thymidylate Synthase ◽  
Locally Advanced ◽  
Neoadjuvant Chemoradiotherapy ◽  
Disease Free Survival ◽  
Advanced Rectal Cancer ◽  
Locally Advanced Rectal Cancer ◽  
Tumour Regression ◽  
The Difference

433 Background: Neoadjuvant fluoropyrimidine-based chemotherapy (ChT) plus radiotherapy (Rt) is a standard approach for locally advanced rectal cancer. Polymorphisms of thymidylate synthase (TS), the target for fluoropyrimidines, are recognized prognostic factors in colon cancer. The aim of this study was to evaluate the prognostic value of the polymorphisms of TS in rectal cancer after neoadjuvant ChT plus Rt. Methods: We studied one-hundred consecutive patients with stage II/III rectal cancer between November 2001 and March 2009. Patients underwent surgery 6-8 weeks after neoadjuvant Rt (5,040 cGy) plus fluoropyrimidine-based ChT. DNA was extracted from paraffin embedded biopsies. TS1494del6 and 5′-28bp repeat +G/C SNP polymorphisms were determined. Results: Sixty-seven percent were men and median age was 67 years. ypT stage was: T0 9%, T1 2%, T2 27%, T3 60% and T4 2%; 32% had locoregional adenopathies. The median follow-up was 45 months and relapse occurred in 20% of patients. Polimorphisms could be determined in 98% of pt: -6bp/-6bp 10%, - 6bp/+6bp 39%, +6bp/+6bp 51% and 2R/2R 72%, 2R/3R 21%, 3R/3R 6%. The grade of pathological tumour regression was not associated with polymorphisms. Relapses occurred in 40% of patients -6bp/-6bp, 22% of patients -6bp/+6bp and 21% of patients +6bp/+6bp. The difference in disease- free survival (DFS) between the first and the third groups was stadistically significative (p=0.049). No relation between 5′-28bp repeat +G/C SNP polymorphism and DFS was found. Conclusions: Our data suggest that the TS1494del6 polimorphism may be an important prognosis factor in rectal cancer receiving neoadjuvant chemoradiotherapy. No significant financial relationships to disclose.

A phase III protocol of androgen suppression (AS) and 3DCRT/IMRT versus AS and 3DCRT/IMRT followed by chemotherapy (CT) with docetaxel and prednisone for localized, high-risk prostate cancer (RTOG 0521).

2015 ◽  
Vol 33 (18_suppl) ◽  
pp. LBA5002-LBA5002 ◽  
Author(s):  
Howard M. Sandler ◽  
Chen Hu ◽  
Seth A. Rosenthal ◽  
Oliver Sartor ◽  
Leonard G. Gomella ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
High Risk ◽  
Survival Rates ◽  
Disease Free Survival ◽  
Phase Iii ◽  
Type I ◽  
Current Standard ◽  
T Stage

LBA5002 Background: High-risk, localized prostate cancer (PCa) patients have a relatively poor prognosis. We hypothesized that the addition of adjuvant docetaxel and prednisone to long-term (24 month) AS and radiation therapy (RT) would improve overall survival (OS). Methods: RTOG 0521 opened December 2005 and closed August 2009 with targeted accrual of 600 cases. It was designed to detect improvement in 4-year OS from 86% to 93% with a 51% hazard reduction (HR = 0.49). Under a 0.05 1-sided type I error and 90% power, at least 78 deaths were required to analyze the OS endpoint. Patients had 1) Gleason (Gl) 7-8, any T-stage, and PSA > 20, or 2) Gl 8, ≥ T2, any PSA, or 3) Gl 9-10, any T-stage, any PSA. All had PSA ≤ 150. RT dose was 75.6 Gy. CT consisted of 6, 21-day cycles of docetaxel + prednisone starting 28 days after RT. Results: Of 612 enrolled, 50 were excluded for eligibility issues, leaving 562 evaluable. Median age = 66, median PSA = 15.1, 53% had Gl 9-10, 27% had cT3-4. Median follow-up = 5.5 yrs. 4-yr OS rates were 89% [95% CI: 84-92%] for the AS+RT arm and 93% [95% CI: 90-96%] for the AS+RT+CT arm (1-sided p = 0.03, HR = 0.68 [95% CI: 0.44, 1.03]). There were 52 centrally-reviewed deaths in the AS+RT arm and 36 in the AS+RT+CT arm, with fewer deaths both due to PCa/treatment (20 vs 16) and due to other causes/unknown (32 vs 20) in the AS+RT+CT arm. 5-yr disease-free survival rates were 66% for AS+RT and 73% for AS+RT+CT (2-sided p = 0.05, HR = 0.76 [95% CI: 0.57, 1.00]). There was 1, Gr 5 unlikely-related adverse event (AE) in the AS+RT arm and 2, Gr 5 possibly/probably-related AEs with AS+RT+CT. Conclusions: For high-risk, localized PCa, adjuvant CT improved the OS from 89% to 93% at 4 years. Toxicity was acceptable. This trial was designed with a short OS assessment period and additional follow-up is warranted to determine the long-term benefit of CT to the current standard of care of long-term AS+RT. This project was supported by grants U10CA21661, U10CA180868, U10CA180822, from the National Cancer Institute and Sanofi with additional support from AstraZeneca for Australian site participation. Clinical trial information: NCT00288080.

Upfront short course radiotherapy (SCRT) in metastatic rectal cancer (mRC): A way forward.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 3570-3570
Author(s):  
Shanu Jain ◽  
Reena Engineer ◽  
Vikas S. Ostwal ◽  
Anant Ramaswamy ◽  
Supriya Chopra ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Locally Advanced ◽  
Progression Free Survival ◽  
R0 Resection ◽  
Distant Disease ◽  
Entire Cohort ◽  
Primary Surgery ◽  
Short Course ◽  
Short Course Radiotherapy

3570 Background: To evaluate the feasibility and efficacy of SCRT followed by chemotherapy (CT) in locally advanced metastatic rectal cancer (LAmRC). Methods: Between May 2012 and August 2015, 70 patients having LAmRC with or without circumferential resection margin (CRM) positive disease treated with SCRT (25Gy/5#) followed by 3-6 cycles of capecitabine/5-FU, oxaliplatin or irinotecan based CT were assessed. Results: Fifty one had single site metastases (23 liver, 16 lung, 10 retroperitoneal lymph nodes and 2 peritoneum), 9 had combined lung and liver metastases and 10 had combined nodal and organ metastases. Sixty five (93%) patients could complete planned SCRT and 3-6 cycles of chemotherapy (starting 7-10 days after RT completion) with dose reduction in 21 (32%) patients owing to CT induced toxicities. Local tumor down-staging was achieved in 43 (61.4%) patients and the rest had a stable primary disease. Radiologically, CRM was free in 25 (46.3%) patients out of 54 initially involved. Surgery of the primary was planned in 38 (58%). R0 resection in 26 (40%), R1 in 7 (pCRM positive). Five refused surgery in spite of being resectable. Rest of the 27 (41%) received palliative CT due to progression of distant disease. Metastatectomy along with primary surgery was done in 16 (25%) patients. Median follow up was 29 months. Overall survival (OS) of entire cohort at 2 years was 40%. Median progression free survival (PFS) and OS of patients with resected primary was 17 (10-24) and 37 (28-45) months, respectively, which is significantly better than those who were not resected (p = < 0.001). Of these 33 resected patients, 13 (39.4%) are disease free and 20 have progressed (16 distant, 2 loco-regional and 2 local and systemic). Conclusions: Upfront SCRT followed by systemic CT in an unresectable group of metastatic rectal cancer patients is safe and feasible and is having encouraging results in terms of downstaging and resectability of the primary. [Table: see text]

Current treatment strategies and patterns of recurrence in locally advanced colon cancer.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e15171-e15171
Author(s):  
Caroline Huynh ◽  
Stephanie Minkova ◽  
Diane Kim ◽  
Heather Stuart ◽  
Trevor D Hamilton
Keyword(s):  
Colon Cancer ◽  
Locally Advanced ◽  
Positive Margin ◽  
Curative Intent ◽  
Free Survival ◽  
Node Negative ◽  
Entire Cohort ◽  
Advanced Colon Cancer ◽  
Patterns Of Recurrence

e15171 Background: Locally advanced colon cancer (LACC) is a frequent presentation and has a high rate of recurrence. The aim of this study was to evaluate current population-based strategies in LACC patients, and to analyze patterns of recurrence. Methods: We conducted a retrospective review of all patients treated at a regional cancer agency with a diagnosis of LACC between 2005 and 2015 treated with curative intent resection. Inclusion criteria were adults with T4 colon cancer, 16 cm above the anal verge, with no evidence of distant metastases. Descriptive statistics were used to define the study population. Kaplan-Meier and Cox-proportional hazards modeling were used for survival analysis. Results: 1394 patients with LACC were reviewed. Median age was 69 [IQR 60-77] and 49.3% were female. Primary tumor location was right-sided in 57.1% of cases. Most tumors were T4a (69.4%) and 39.4% were node positive. A total of 35.4% had urgent/emergent surgery, 46.4% were at least partially obstructed, 22.0% were perforated and 1.9% had a diverting ostomy as an initial operation. En-bloc multi-visceral resection occurred in 23.5% of cases. Positive margins were present in 14.3%. Only 1.6% had neoadjuvant chemotherapy and 0.8% had neoadjuvant chemoradiation. Adjuvant chemotherapy was delivered in 59.8% and adjuvant chemoradiation in 2.8%. Median follow up was 37 months. During follow up 681 (48.9%) patients died and 584 (41.9%) patients developed recurrence. In the entire cohort, rates of recurrences were local-regional (14.7%) and distant metastatic (35.1%). Overall survival for the entire cohort was 63 months [95% CI 55.7-70.3] and recurrence-free survival was 61 months [95% CI 38.8-83.2]. Multivariate analysis identified age (HR 1.03, 95% CI [1.02-1.05] p < 0.001), node negative status (HR 0.62, 95% CI [0.45-0.84] p = 0.002) and positive margin (HR 1.79, 95% CI [1.24-2.57] p = 0.002) as predictive of overall survival after adjusting for confounding factors. Predictive factors for recurrence-free survival were node negative status (HR 0.55, 95% CI [0.39-0.77] p < 0.001) and positive margin (HR 1.51, 95% CI [1.02-2.23] p = 0.038). Conclusions: Recurrence after curative intent treatment for LACC is common. Recurrence and survival patterns are significantly influenced by tumor nodal status and margin positivity.

ERDAFITINIB in locally advanced or metastatic urothelial carcinoma (mUC): Long-term outcomes in BLC2001.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 5015-5015 ◽  
Author(s):  
Arlene O. Siefker-Radtke ◽  
Andrea Necchi ◽  
Se Hoon Park ◽  
Jesús García-Donas ◽  
Robert A Huddart ◽  
...  
Keyword(s):  
Safety Profile ◽  
Objective Response ◽  
Locally Advanced ◽  
Optimal Schedule ◽  
Safety Data ◽  
Serum Phosphate Level ◽  
Primary Analysis ◽  
Platinum Based Chemotherapy

5015 Background: Erdafitinib (JNJ-42756493; ERDA) is the only pan-FGFR kinase inhibitor with US FDA approval for treatment of adults with mUC with susceptible FGFR3/2 alterations (alt) and who progressed on ≥ 1 line of prior platinum-based chemotherapy (chemo). Approval was based on data from the primary analysis of the pivotal BLC2001 trial1. Here we report long-term efficacy and safety data from the 8 mg/d continuous dose regimen in BLC2001. Methods: BLC2001 (NCT02365597) is a global, open-label, phase 2 trial of pts with measurable mUC with prespecified FGFR alt, ECOG 0-2, and progression during/following ≥ 1 line of prior chemo or ≤ 12 mos of (neo)adjuvant chemo, or were cisplatin ineligible, chemo naïve. The optimal schedule of ERDA determined in the initial part of the study was 8 mg/d continuous ERDA in 28-d cycles with uptitration to 9 mg/d (ERD 8 mg UpT) if a protocol-defined target serum phosphate level was not reached and if no significant treatment-related adverse events (TRAEs) occurred. Primary end point was the confirmed objective response rate (ORR=% complete response + % partial response). Key secondary end points were progression-free survival (PFS), duration of response (DOR) and overall survival (OS). Results: Median follow-up for 101 patients treated with ERDA 8 mg UpT was ~24 months. Confirmed ORR was 40%. Median DOR was 5.98 mos; 31% of responders had DOR ≥ 1 yr. Median PFS was 5.52 mos, median OS was 11.3 mos. 12-mos and 24-mos survival rates were 49% and 31%, respectively. Median treatment duration was 5.4 mos. The ERDA safety profile was consistent with the primary analysis. No new TRAEs were seen with longer follow-up. Central serous retinopathy (CSR) events occurred in 27% (27/101) of patients; 85% (23/27) were Grade 1 or 2; dosage was reduced in 13 pts, interrupted for 8, and discontinued for 3. On the data cut-off date, 63% (17/27) had resolved; 60% (6/10) of ongoing CSR events were Grade 1. There were no treatment-related deaths. Conclusions: With a median follow-up of 2 yrs, ERDA in mUC + FGFR alt showed a manageable safety profile and consistent efficacy, with median OS of 11.3 mos. 31% had a DOR ≥12 mos and 31% were alive at 24 mos. ERDA monotherapy vs. immune checkpoint inhibitor (PD-1) or chemo is being further analyzed in a randomized control study (THOR; NCT03390504).Reference: Loriot Y, et al. N Engl J Med. 2019;381:338-48. Clinical trial information: NCT02365597 .

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