Invasive urothelial cancer (iUC) with FGFR3 hotspot mutation/fusion (FGFR3+): A molecularly and clinically distinctive entity?

2019 ◽  
Vol 37 (7_suppl) ◽  
pp. 459-459
Author(s):  
Jose Mauricio S. C. Mota ◽  
Min Yuen Teo ◽  
Han Li ◽  
Arjun Vasant Balar ◽  
Matthew I. Milowsky ◽  
...  
Keyword(s):  
Urothelial Cancer ◽  
Progression Free Survival ◽  
Standard Of Care ◽  
Study Objective ◽  
Free Survival ◽  
Non Invasive ◽  
Genomic Landscape ◽  
Platinum Based Chemotherapy ◽  
Hotspot Mutations ◽  
Muscle Invasive

459 Background: FGFR3+ is ubiquitous in non-invasive UC but found in ~16% of iUC. We sought to characterize the genomic landscape and response to platinum-based chemotherapy (ctx) of FGFR3+ iUC in the neoadjuvant (NAC) and metastatic (mUC) setting. Methods: Two molecularly-characterized cohorts were used for the study objective: (1) NAC-treated muscle invasive UC, incorporating consecutively sequenced standard of care UC and patients (pts) from a phase II trial (Iyer et al, JCO 2018); (2) mUC treated with platinum ctx, with FGFR3- mUC from a published work (Teo et al, CCR 2017) serving as comparator. iUC with hotspot mutations / fusions were considered FGFR3+. Clinical outcomes and frequency of altered genes were compared. Results: In the NAC cohort, 87 pts were identified (NAC response: pT0 [n = 20, 23%], <pT2 [n = 22, 25%], ≥pT2 [n = 45, 52%]). FGFR3+ (n = 11, 13%) was associated with a trend towards poor NAC response and was found in 0/20 pT0 (0%), 3/22 <pT2 (14%) and 8/45 ≥pT2 (18%) (Cochran-Armitage, p=0.06). Among ≥pT2 tumors, FGFR3+ was associated with shorter recurrence-free survival (3.7 vs 17.6 months; HR 4.8 95% CI 1.9–12.1). 49 FGFR3+ mUC pts were identified and compared to FGFR3- mUC (n = 82). FGFR3+ had a numerically higher rate of lung metastasis (42% vs 29%, p = 0.25). 1st line therapies included: platinum-based ctx (n = 27), non-platinum ctx (n = 4), immunotherapy (IO, n = 13), ctx + IO (n = 4), and FGFR inhibitor (n = 1). Platinum ctx response rate for 21/27 evaluable FGFR3+ pts was 40%. FGFR3+ mUC had similar overall survival (OS, median 25.7 vs 15.8 months, HR 0.7, 95%CI 0.4-1.2; 1-year OS: 70% vs 59%) and progression-free survival (median: 7.2 vs 7.1 months, HR 1.3, 95% CI 0.8-2.1). Frequencies of altered genes are tabulated. No differences in mutational load were seen. Conclusions: FGFR3+ iUC is a genomically distinct subset of iUC. Despite low responses to NAC ctx, FGFR3+ had similar responses, PFS, and OS in the mUC setting. [Table: see text]

scholarly journals Randomized Double-Blind Phase II Study of Maintenance Pembrolizumab Versus Placebo After First-Line Chemotherapy in Patients With Metastatic Urothelial Cancer

2020 ◽  
Vol 38 (16) ◽  
pp. 1797-1806 ◽  
Author(s):  
Matthew D. Galsky ◽  
Amir Mortazavi ◽  
Matthew I. Milowsky ◽  
Saby George ◽  
Sumati Gupta ◽  
...  
Keyword(s):  
Overall Survival ◽  
Stable Disease ◽  
Urothelial Cancer ◽  
Progression Free Survival ◽  
Maximum Efficiency ◽  
First Line ◽  
Double Blind ◽  
Free Survival ◽  
Metastatic Urothelial Cancer ◽  
Platinum Based Chemotherapy

PURPOSE Platinum-based chemotherapy for first-line treatment of metastatic urothelial cancer is typically administered for a fixed duration followed by observation until progression. “Switch maintenance” therapy with PD-1 blockade at the time of chemotherapy cessation may be attractive for mechanistic and pragmatic reasons. PATIENTS AND METHODS Patients with metastatic urothelial cancer achieving at least stable disease on first-line platinum-based chemotherapy were enrolled. Patients were randomly assigned double-blind 1:1 to switch maintenance pembrolizumab 200 mg intravenously once every 3 weeks versus placebo for up to 24 months. Patients with disease progression on placebo could cross over to pembrolizumab. The primary objective was to determine the progression-free survival. Secondary objectives included determining overall survival as well as treatment outcomes according to PD-L1 combined positive score (CPS). RESULTS Between December 2015 and November 2018, 108 patients were randomly assigned to pembrolizumab (n = 55) or placebo (n = 53). The objective response rate was 23% with pembrolizumab and 10% with placebo. Treatment-emergent grade 3-4 adverse events occurred in 59% receiving pembrolizumab and 38% of patients receiving placebo. Progression-free survival was significantly longer with maintenance pembrolizumab versus placebo (5.4 months [95% CI, 3.1 to 7.3 months] v 3.0 months [95% CI; 2.7 to 5.5 months]; hazard ratio, 0.65; log-rank P = .04; maximum efficiency robust test P = .039). Median overall survival was 22 months (95% CI, 12.9 months to not reached) with pembrolizumab and 18.7 months (95% CI, 11.4 months to not reached) with placebo. There was no significant interaction between PD-L1 CPS ≥ 10 and treatment arm for progression-free survival or overall survival. CONCLUSION Switch maintenance pembrolizumab leads to additional objective responses in patients achieving at least stable disease with first-line platinum-based chemotherapy and prolongs progression-free survival in patients with metastatic urothelial cancer.

Randomized double-blind phase II study of maintenance pembrolizumab versus placebo after first-line chemotherapy in patients (pts) with metastatic urothelial cancer (mUC): HCRN GU14-182.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 4504-4504 ◽  
Author(s):  
Matt D. Galsky ◽  
Sumanta K. Pal ◽  
Amir Mortazavi ◽  
Matthew I. Milowsky ◽  
Saby George ◽  
...  
Keyword(s):  
Urothelial Cancer ◽  
Objective Response ◽  
Progression Free Survival ◽  
Primary Objective ◽  
Maximum Efficiency ◽  
Double Blind ◽  
Free Survival ◽  
Metastatic Urothelial Cancer ◽  
Platinum Based Chemotherapy ◽  
Line Chemotherapy

4504 Background: Platinum-based chemotherapy for 1st-line treatment of pts with metastatic urothelial cancer (mUC) is typically administered for a fixed duration followed by observation until recurrence. PD-1 blockade with pembro improves survival of pts with mUC progressing despite platinum-based chemotherapy. We explored the potential benefit of earlier use of PD-1 blockade using a "switch maintenance" approach. Methods: Pts with mUC achieving at least stable disease after up to 8 cycles of 1st-line platinum-based chemotherapy were enrolled. Pts were randomized 1:1 to pembro 200 mg IV q3 weeks versus placebo for up to 24 months; pts progressing on placebo could cross over to pembro. Randomization was stratified based on pre-chemotherapy visceral metastases (Y/N) and response to 1st-line chemotherapy (CR/PR vs. SD). The primary objective was to determine the progression-free survival (PFS) as per irRECIST among pts treated with pembro versus placebo. Results: Between 12/2015 and 11/2018, 107 pts were randomized to placebo (n=52) versus pembro (n=55). The baseline pt characteristics are shown in the Table. Pts randomized to placebo and pembro received a median of 6 and 8 cycles, respectively. Excluding patients with baseline CRs, the objective response rate was 12% (5/42) on placebo and 22% (10/46) on pembro. Grade 3-4 treatment emergent adverse events occurred in 48% of pts on placebo and 56% on pembro. At a median follow-up of 14.7 months, 41 pts have died and 26/52 pts randomized to placebo have crossed over to pembro. PFS was significantly longer in patients randomized to pembro vs. placebo (Maximum Efficiency Robust Test p=0.036; log-rank p = 0.038). The 18-month restricted mean progression-free survival time was 5.6 months with placebo and 8.2 months with pembro (p=0.023). Conclusions: Switch maintenance pembro may “deepen” responses achieved with 1st-line chemotherapy. Switch maintenance pembro prolongs PFS in pts with mUC completing 1st-line platinum-based chemotherapy. Clinical trial information: NCT02500121. [Table: see text]

scholarly journals Current FDA-Approved Therapies for High-Grade Malignant Gliomas

Biomedicines ◽  
2021 ◽  
Vol 9 (3) ◽  
pp. 324
Author(s):  
Jacob P. Fisher ◽  
David C. Adamson
Keyword(s):  
Controlled Trial ◽  
Malignant Gliomas ◽  
Progression Free Survival ◽  
Standard Of Care ◽  
High Grade ◽  
Tumor Treatment ◽  
Free Survival ◽  
Randomized Controlled ◽  
Significant Survival ◽  
One Year

The standard of care (SOC) for high-grade gliomas (HGG) is maximally safe surgical resection, followed by concurrent radiation therapy (RT) and temozolomide (TMZ) for 6 weeks, then adjuvant TMZ for 6 months. Before this SOC was established, glioblastoma (GBM) patients typically lived for less than one year after diagnosis, and no adjuvant chemotherapy had demonstrated significant survival benefits compared with radiation alone. In 2005, the Stupp et al. randomized controlled trial (RCT) on newly diagnosed GBM patients concluded that RT plus TMZ compared to RT alone significantly improved overall survival (OS) (14.6 vs. 12.1 months) and progression-free survival (PFS) at 6 months (PFS6) (53.9% vs. 36.4%). Outside of TMZ, there are four drugs and one device FDA-approved for the treatment of HGGs: lomustine, intravenous carmustine, carmustine wafer implants, bevacizumab (BVZ), and tumor treatment fields (TTFields). These treatments are now mainly used to treat recurrent HGGs and symptoms. TTFields is the only treatment that has been shown to improve OS (20.5 vs. 15.6 months) and PFS6 (56% vs. 37%) in comparison to the current SOC. TTFields is the newest addition to this list of FDA-approved treatments, but has not been universally accepted yet as part of SOC.

scholarly journals Phase II Trial of Cetuximab With or Without Paclitaxel in Patients With Advanced Urothelial Tract Carcinoma

2012 ◽  
Vol 30 (28) ◽  
pp. 3545-3551 ◽  
Author(s):  
Yu-Ning Wong ◽  
Samuel Litwin ◽  
David Vaughn ◽  
Seth Cohen ◽  
Elizabeth R. Plimack ◽  
...  
Keyword(s):  
Phase Ii ◽  
Urothelial Cancer ◽  
Single Agent ◽  
Progression Free Survival ◽  
Salvage Chemotherapy ◽  
Free Survival ◽  
Metastatic Urothelial Cancer ◽  
Metastatic Setting ◽  
Previously Treated ◽  
Grade 3

Purpose The benefit of salvage chemotherapy is modest in metastatic urothelial cancer. We conducted a randomized, noncomparative phase II study to measure the efficacy of cetuximab with or without paclitaxel in patients with previously treated urothelial cancer. Patients and Methods Patients with metastatic urothelial cancer who received one line of chemotherapy in the perioperative or metastatic setting were randomly assigned to 4-week cycles of cetuximab 250 mg/m2 with or without paclitaxel 80 mg/m2 per week. We used early progression as an indicator of futility. Either arm would close if seven of the initial 15 patients in that arm progressed at the first disease evaluation at 8 weeks. Results We enrolled 39 evaluable patients. The single-agent cetuximab arm closed after nine of the first 11 patients progressed by 8 weeks. The combination arm completed the full accrual of 28 patients, of whom 22 patients (78.5%) had visceral disease. Twelve of 28 patients had progression-free survival greater than 16 weeks. The overall response rate was 25% (95% CI, 11% to 45%; three complete responses and four partial responses). The median progression-free survival was 16.4 weeks (95% CI, 12 to 25.1 weeks), and the median overall survival was 42 weeks (95% CI, 30.4 to 78 weeks). Treatment-related grade 3 and 4 adverse events that occurred in at least two patients were rash (six cases), fatigue (five cases), and low magnesium (three cases). Conclusion Although it had limited activity as a single agent, cetuximab appears to augment the antitumor activity of paclitaxel in previously treated urothelial cancers. The cetuximab and paclitaxel combination merits additional study to establish its role in the treatment of urothelial cancers.

scholarly journals Phase II trial of the IDO pathway inhibitor indoximod plus pembrolizumab for the treatment of patients with advanced melanoma

2021 ◽  
Vol 9 (6) ◽  
pp. e002057
Author(s):  
Yousef Zakharia ◽  
Robert R McWilliams ◽  
Olivier Rixe ◽  
Joseph Drabick ◽  
Montaser F Shaheen ◽  
...  
Keyword(s):  
Phase Ii ◽  
Single Agent ◽  
Objective Response ◽  
Progression Free Survival ◽  
Standard Of Care ◽  
Complete Response ◽  
Advanced Melanoma ◽  
Free Survival ◽  
Programmed Death ◽  
Evaluable Population

BackgroundThe indoleamine 2,3-dioxygenase (IDO) pathway is a key counter-regulatory mechanism that, in cancer, is exploited by tumors to evade antitumor immunity. Indoximod is a small-molecule IDO pathway inhibitor that reverses the immunosuppressive effects of low tryptophan (Trp) and high kynurenine (Kyn) that result from IDO activity. In this study, indoximod was used in combination with a checkpoint inhibitor (CPI) pembrolizumab for the treatment for advanced melanoma.MethodsPatients with advanced melanoma were enrolled in a single-arm phase II clinical trial evaluating the addition of indoximod to standard of care CPI approved for melanoma. Investigators administered their choice of CPI including pembrolizumab (P), nivolumab (N), or ipilimumab (I). Indoximod was administered continuously (1200 mg orally two times per day), with concurrent CPI dosed per US Food and Drug Administration (FDA)-approved label.ResultsBetween July 2014 and July 2017, 131 patients were enrolled. (P) was used more frequently (n=114, 87%) per investigator’s choice. The efficacy evaluable population consisted of 89 patients from the phase II cohort with non-ocular melanoma who received indoximod combined with (P).The objective response rate (ORR) for the evaluable population was 51% with confirmed complete response of 20% and disease control rate of 70%. Median progression-free survival was 12.4 months (95% CI 6.4 to 24.9). The ORR for Programmed Death-Ligand 1 (PD-L1)-positive patients was 70% compared with 46% for PD-L1-negative patients. The combination was well tolerated, and side effects were similar to what was expected from single agent (P).ConclusionIn this study, the combination of indoximod and (P) was well tolerated and showed antitumor efficacy that is worth further evaluation in selected patients with advanced melanoma.

Salvage immune checkpoint inhibitor (ICI) plus tyrosine kinase inhibitor (TKI) combination therapy for metastatic renal cell carcinoma (mRCC).

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e16567-e16567
Author(s):  
Anish B. Parikh ◽  
Sarah P. Psutka ◽  
Yuanquan Yang ◽  
Katharine Collier ◽  
Abdul Miah ◽  
...  
Keyword(s):  
Combination Therapy ◽  
Immune Checkpoint Inhibitor ◽  
Kinase Inhibitor ◽  
Objective Response ◽  
Progression Free Survival ◽  
Standard Of Care ◽  
Free Survival ◽  
Kaplan Meier ◽  
Grade 3 ◽  
Combination Regimens

e16567 Background: ICI/TKI combinations are a new standard of care for the initial treatment (tx) of mRCC. Efficacy and toxicity of such combination regimens beyond the first-line (1L) setting remain unknown. Methods: We retrospectively reviewed charts for adult patients (pts) receiving an ICI/TKI combination in any line of tx for mRCC of any histology at one of two academic centers as of May 1, 2020. ICIs included pembrolizumab (Pm), nivolumab (Ni), ipilimumab (Ip), or avelumab (Av); TKIs included sunitinib (Su), axitinib (Ax), pazopanib (Pz), lenvatinib (Ln), or cabozantinib (Ca). Clinical data including pt demographics, histology, International mRCC Database Consortium (IMDC) risk group, tx history, and ICI/TKI tx and toxicity details were recorded. Outcomes included objective response rate (ORR), median progression-free survival (mPFS), and safety, analyzed via descriptive statistics and the Kaplan-Meier method. Results: Of 85 pts, 69 (81%) were male and 67 (79%) had clear cell histology. IMDC risk was favorable (24%), intermediate (54%), poor (20%), and unknown (2%). 39% had ICI/TKI tx in the 1L setting. ICI/TKI regimens included Pm/Ax (33%), Ni/Ca (25%), Ni/Ax (20%), Av/Ax (11%), Ni/Ip/Ca (8%), Ni/Su (2%), and Ni/Ln (1%). ORR and mPFS stratified by line of tx and prior tx are shown in the table. Of 52 pts who received ICI/TKI tx as salvage (after 1L), 52% had a grade 3 or higher (≥G3) adverse event (AE), of which the most common were anorexia (13.5%), diarrhea and hypertension (11.5% each), and fatigue (9.6%). 65% of pts on salvage ICI/TKI tx stopped tx for progression/death, while 16% stopped tx for ≥G3 AE. ≥G3 AE rates by line of tx were 62.5% (2L), 50% (3L), and 45% (≥4L). Conclusions: ICI/TKI combination therapy is effective and safe beyond the 1L setting. Prior tx history appears to impact efficacy but has less of an effect on safety/tolerability. These observations will need to be confirmed in prospective studies.[Table: see text]

Phase II consolidation trial with anti-Lewis-Y monoclonal antibody (hu3S193) in platinum-sensitive ovarian cancer after a second remission

2021 ◽  
pp. ijgc-2020-002239
Author(s):  
Oren Smaletz ◽  
Gustavo Ismael ◽  
Maria Del Pilar Estevez-Diz ◽  
Ivana L O Nascimento ◽  
Ana Luiza Gomes de Morais ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Monoclonal Antibody ◽  
Epithelial Ovarian Cancer ◽  
Phase Ii ◽  
Progression Free Survival ◽  
Complete Response ◽  
Free Survival ◽  
Platinum Sensitive ◽  
Platinum Based Chemotherapy ◽  
Lewis Y

ObjectiveTo investigate the efficacy and safety of hu3S193, a humanized anti-Lewis-Y monoclonal antibody, as a consolidation strategy in patients with platinum-sensitive recurrent epithelial ovarian cancer who achieved a second complete response after salvage platinum-doublet chemotherapy.MethodsThis single-arm phase II study accrued patients with recurrent epithelial ovarian cancer with Lewis-Y expression by immunohistochemistry who had achieved a second complete response after five to eight cycles of platinum-based chemotherapy. Patients received intravenous infusions of hu3S193, 30 mg/m2 every 2 weeks starting no more than 8 weeks after the last dose of chemotherapy and continuing for 12 doses, until disease progression, or unacceptable toxicity. The primary endpoint was progression-free survival of the second remission. Secondary objectives were safety and pharmacokinetics.ResultsTwenty-nine patients were enrolled. Most had a papillary/serous histology tumor (94%), stage III disease at diagnosis (75%), and five (17%) underwent secondary cytoreduction before salvage chemotherapy. Two patients were not eligible for efficacy but were considered for toxicity analysis. Eighteen patients (62%) completed the full consolidation treatment while nine patients progressed on treatment. At the time of analysis, 23 patients (85%) of the eligible population had progressed and seven of these patients (26%) had died. Median progression-free survival of the second remission was 12.1 months (95% CI: 10.6–13.9), with a 1-year progression-free survival of the second remission rate of 50.1%. The trial was terminated early since it was unlikely that the primary objective would be achieved. The most commonly reported treatment-related adverse events were nausea (55%) and vomiting (51%).ConclusionsHu3S193 did not show sufficient clinical activity as consolidation therapy in patients with recurrent epithelial ovarian cancer who achieved a second complete response after platinum-based chemotherapy.Trial registrationNCT01137071.

scholarly journals Combined BRAF and MEK Inhibition with Vemurafenib and Cobimetinib for Patients with Advanced Melanoma

2017 ◽  
Vol 13 (01) ◽  
pp. 1
Author(s):  
Antonio M Grimaldi ◽  
Ester Simeone ◽  
Lucia Festino ◽  
Vito Vanella ◽  
Paolo A Ascierto ◽  
...  
Keyword(s):  
Mapk Pathway ◽  
Combined Therapy ◽  
Acquired Resistance ◽  
Braf Inhibitor ◽  
Progression Free Survival ◽  
Standard Of Care ◽  
Phase Iii ◽  
Free Survival ◽  
Mek Inhibition ◽  
Braf Mutant

Acquired resistance is the most common cause of BRAF inhibitor monotherapy treatment failure, with the majority of patients experiencing disease progression with a median progression-free survival of 6-8 months. As such, there has been considerable focus on combined therapy with dual BRAF and MEK inhibition as a means to improve outcomes compared with monotherapy. In the COMBI-d and COMBI-v trials, combined dabrafenib and trametinib was associated with significant improvements in outcomes compared with dabrafenib or vemurafenib monotherapy, in patients with BRAF-mutant metastatic melanoma. The combination of vemurafenib and cobimetinib has also been investigated. In the phase III CoBRIM study in patients with unresectable stage III-IV BRAF-mutant melanoma, treatment with vemurafenib and cobimetinib resulted in significantly longer progression-free survival and overall survival (OS) compared with vemurafenib alone. One-year OS was 74.5% in the vemurafenib and cobimetinib group and 63.8% in the vemurafenib group, while 2-year OS rates were 48.3% and 38.0%, respectively. The combination was also well tolerated, with a lower incidence of cutaneous squamous-cell carcinoma and keratoacanthoma compared with monotherapy. Dual inhibition of both MEK and BRAF appears to provide a more potent and durable anti-tumour effect than BRAF monotherapy, helping to prevent acquired resistance as well as decreasing adverse events related to BRAF inhibitor-induced activation of the MAPK-pathway. Combined BRAF and MEK inhibition is the standard of care in patients with advanced BRAF-mutant melanoma.

scholarly journals Restaging Transurethral Resection of Bladder Tumours after BCG Immunotherapy Induction in Patients with T1 Non-Muscle-Invasive Bladder Cancer Might not Be Associated with Oncologic Benefit

2020 ◽  
Vol 9 (10) ◽  
pp. 3306
Author(s):  
Wojciech Krajewski ◽  
Marco Moschini ◽  
Łukasz Nowak ◽  
Sławomir Poletajew ◽  
Andrzej Tukiendorf ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Transurethral Resection ◽  
Tertiary Care ◽  
Survival Rates ◽  
Progression Free Survival ◽  
Recurrence Free Survival ◽  
Muscle Invasive Bladder Cancer ◽  
Free Survival ◽  
Muscle Invasive ◽  
Bladder Tumours

Background and Purpose: The European Association of Urology guidelines recommend restaging transurethral resection of bladder tumours (reTURB) 2–6 weeks after primary TURB. However, in clinical practice some patients undergo a second TURB procedure after Bacillus Calmette-Guérin immunotherapy (BCG)induction. To date, there are no studies comparing post-BCG reTURB with the classic pre-BCG approach. The aim of this study was to assess whether the performance of reTURB after BCG induction in T1HG bladder cancer is related to potential oncological benefits. Materials and Methods: Data from 645 patients with primary T1HG bladder cancer treated between 2001 and 2019 in 12 tertiary care centres were retrospectively reviewed. The study included patients who underwent reTURB before BCG induction (Pre-BCG group: 397 patients; 61.6%) and those who had reTURB performed after BCG induction (Post-BCG group: 248 patients, 38.4%). The decision to perform reTURB before or after BCG induction was according to the surgeon’s discretion, as well as a consideration of local proceedings and protocols. Due to variation in patients’ characteristics, both propensity-score-matched analysis (PSM) and inverse-probability weighting (IPW) were implemented. Results: The five-year recurrence-free survival (RFS) was 64.7% and 69.1% for the Pre- and Post-BCG groups, respectively, and progression-free survival (PFS) was 82.7% and 83.3% for the Pre- and Post-BCG groups, respectively (both: p > 0.05). Similarly, neither RFS nor PFS differed significantly for a five-year period or in the whole time of observation after the PSM and IPW matching methods were used. Conclusions: Our results suggest that there might be no difference in recurrence-free survival and progression-free survival rates, regardless of whether patients have reTURB performed before or after BCG induction.

scholarly journals Induction Chemotherapy Followed by Cetuximab Radiotherapy Is Not Superior to Concurrent Chemoradiotherapy for Head and Neck Carcinomas: Results of the GORTEC 2007-02 Phase III Randomized Trial

2018 ◽  
Vol 36 (31) ◽  
pp. 3077-3083 ◽  
Author(s):  
Lionnel Geoffrois ◽  
Laurent Martin ◽  
Dominique De Raucourt ◽  
Xu Shan Sun ◽  
Yungan Tao ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Induction Chemotherapy ◽  
Squamous Cell ◽  
Concurrent Chemoradiotherapy ◽  
Progression Free Survival ◽  
Standard Of Care ◽  
Phase Iii ◽  
Free Survival

Purpose Both concurrent chemoradiotherapy (CT-RT) and cetuximab radiotherapy (cetux-RT) have been established as the standard of care for the treatment of locally advanced squamous cell carcinoma of the head and neck. It was not known whether the addition of induction chemotherapy before cetux-RT could improve outcomes compared with standard of care CT-RT. Patients and Methods The current trial was restricted to patients with nonmetastatic N2b, N2c, or N3 squamous cell carcinoma of the head and neck and fit for taxotere, cisplatin, fluorouracil (TPF). Patients were randomly assigned to receive three cycles of TPF followed by cetux-RT versus concurrent carboplatin fluorouracil and RT as recommended in National Comprehensive Cancer Network guidelines. The trial was powered to detect a hazard ratio (HR) of 0.66 in favor of TPF plus cetux-RT for progression-free survival at 2 years. The inclusion of 180 patients per arm was needed to achieve 80% power at a two-sided significance level of .05. Results Between 2009 and 2013, 370 patients were included. All patients and tumors characteristics were well balanced between arms. There were more cases of grade 3 and 4 neutropenia in the induction arm, and the induction TPF was associated with 6.6% treatment-related deaths. With a median follow-up of 2.8 years, 2-year progression-free survival was not different between both arms (CT-RT, 0.38 v TPF + cetux-RT, 0.36; HR, 0.93 [95% CI, 0.73 to 1.20]; P = .58). HR was 0.98 (95% CI, 0.74 to 1.3; P = .90) for locoregional control and 1.12 (95% CI, 0.86 to 1.46; P = .39) for overall survival. These effects were observed regardless of p16 status. The rate of distant metastases was lower in the TPF arm (HR, 0.54 [95% CI, 0.30 to 0.99]; P = .05). Conclusion Induction TPF followed by cetux-RT did not improve outcomes compared with CT-RT in a population of patients with advanced cervical lymphadenopathy.

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