scholarly journals Safety and efficacy of single cycle induction treatment with cisplatin/docetaxel/ durvalumab/tremelimumab in locally advanced HNSCC: first results of CheckRad-CD8

2020 ◽  
Vol 8 (2) ◽  
pp. e001378
Author(s):  
Markus Hecht ◽  
Antoniu Oreste Gostian ◽  
Markus Eckstein ◽  
Sandra Rutzner ◽  
Jens von der Grün ◽  
...  
Keyword(s):  
Cell Density ◽  
Univariate Analysis ◽  
Locally Advanced ◽  
Induction Treatment ◽  
Single Cycle ◽  
Safety And Efficacy ◽  
Cd8 Cells ◽  
Programmed Death ◽  
Cd8 Cell ◽  
Grade 3

BackgroundTo determine safety and efficacy of single cycle induction treatment with cisplatin/docetaxel and durvalumab/tremelimumab in stage III-IVB head and neck cancer.MethodsPatients received a single cycle of cisplatin 30 mg/m² on days 1–3 and docetaxel 75 mg/m² on day 1 combined with durvalumab 1500 mg fix dose on day 5 and tremelimumab 75 mg fix dose on day 5. Patients with pathologic complete response (pCR) in the rebiopsy after induction treatment or at least 20% increase of intratumoral CD8+ cell density in the rebiopsy compared with baseline entered radioimmunotherapy with concomitant durvalumab/tremelimumab. The objective of this interim analysis was to analyze safety and efficacy of the chemoimmunotherapy-induction treatment before radioimmunotherapy.ResultsA total of 57 patients were enrolled, 56 were treated. Median pretreatment intratumoral CD8+ cell density was 342 cells/mm². After induction treatment, 27 patients (48%) had a pCR in the rebiopsy and further 25 patients (45%) had a relevant increase of intratumoral CD8+ cells (median increase by a factor of 3.0). Adverse event (AE) grade 3–4 appeared in 38 patients (68%) and mainly consisted of leukopenia (43%) and infections (29%). Six patients (11%) developed grade 3–4 immune-related AE. Univariate analysis computed p16 positivity, programmed death ligand 1 immune cell area and intratumoral CD8+ cell density as predictors of pCR. On multivariable analysis, intratumoral CD8+ cell density predicted pCR independently (OR 1.0012 per cell/mm², 95% CI 1.0001 to 1.0022, p=0.016). In peripheral blood CD8+ cells, the coexpression of programmed death protein 1 significantly increased especially in patients with pCR.ConclusionsSingle cycle induction treatment with cisplatin/docetaxel and durvalumab/tremelimumab is feasible and achieves a high biopsy-proven pCR rate.

A multicenter phase II trial of the combination cisplatin/ docetaxel/durvalumab/tremelimumab as single-cycle induction treatment in locally advanced HNSCC (CheckRad-CD8 trial).

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 6519-6519 ◽  
Author(s):  
Markus Hecht ◽  
Antoniu-Oreste Gostian ◽  
Markus Eckstein ◽  
Sandra Rutzner ◽  
Jens von der Grün ◽  
...  
Keyword(s):  
Phase Ii ◽  
Phase Ii Trial ◽  
Cell Cancer ◽  
Locally Advanced ◽  
Multivariable Analysis ◽  
Induction Treatment ◽  
Single Cycle ◽  
Cd8 Cells ◽  
Multicenter Phase ◽  
Grade 3

6519 Background: PD-1/PD-L1 inhibitors are efficient in head and neck squamous cell cancer (HNSCC). Combination with anti-CTLA4 agents may enhance anti-tumor activity compared to anti-PD-1/PD-L1 monotherapy in different tumor types. In the CheckRad-CD8 trial the typical induction treatment consisting of Cisplatin/Docetaxel was combined with Durvalumab/Tremelimumab. Patients with pathological complete response (pCR) in the re-biopsy after induction treatment or at least 20% increase of intratumoral CD8 density in the re-biopsy compared to baseline entered radioimmunotherapy with concomitant Durvalumab/Tremelimumab. Methods: In this prospective multicenter phase II trial, patients with HNSCC stage III-IVB received a single cycle of Cisplatin 30mg/m² d1-3, Docetaxel 75mg/m² d1, Durvalumab 1500mg fix dose d5 and Tremelimumab 75mg fix dose d5. Objectives of this interim analysis were to quantify the effect of the induction treatment on intratumoral CD8 density and the pCR rate and to generate safety data. Results: Between Sep 2018 and Dec 2019, 57 patients were enrolled. Median age was 59 years, 22 patients (37%) were current smokers, 27 patients (47%) had oropharyngeal tumors (52% p16 positive). The median pre-treatment intratumoral CD8 density was 335 CD8+ cells/mm². After induction treatment 27 patients (47%) had a pCR in the re-biopsy and further 25 patients (44%) had a relevant increase of intratumoral CD8+ cells (median increase by factor 3.0). Response according to RECIST criteria was CR in 1 (2%), PR in 19 (33%) and SD in 20 patients (35%) (17 patients not evaluable). Adverse events (AE) grade 3-4 appeared in 39 patients (68%) and mainly consisted of leucopenia (43%) and infections (28%). 6 patients (11%) developed grade 3-4 immune-related AEs. In multivariable analysis the intratumoral CD8 density was the only independently significant predictor of pCR (odds ratio 1.0013 per cell/mm², 95%-CI 1.00023-1.0023, p=0.017). 42 patients (74%) continued with Durvalumab/ Tremelimumab concomitant to radiotherapy. Conclusions: Single cycle induction treatment with Cisplatin/Docetaxel/Durvalumab/Tremelimumab is feasible and achieves a high pCR rate. CD8 density may have a predictive role for further treatment planning in locally advanced HNSCC. Clinical trial information: NCT03426657 .

scholarly journals Carbon ion radiotherapy for prostate cancer with bladder invasion

BMC Urology ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Yuhei Miyasaka ◽  
Hidemasa Kawamura ◽  
Hiro Sato ◽  
Nobuteru Kubo ◽  
Tatsuji Mizukami ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Locally Advanced ◽  
Therapeutic Benefit ◽  
Carbon Ion Radiotherapy ◽  
Safety And Efficacy ◽  
Carbon Ion ◽  
Grade 3 ◽  
Bladder Invasion

Abstract Background The optimal management of clinical T4 (cT4) prostate cancer (PC) is still uncertain. At our institution, carbon ion radiotherapy (CIRT) for nonmetastatic PC, including tumors invading the bladder, has been performed since 2010. Since carbon ion beams provide a sharp dose distribution with minimal penumbra and have biological advantages over photon radiotherapy, CIRT may provide a therapeutic benefit for PC with bladder invasion. Hence, we evaluated CIRT for PC with bladder invasion in terms of the safety and efficacy. Methods Between March 2010 and December 2016, a total of 1337 patients with nonmetastatic PC received CIRT at a total dose of 57.6 Gy (RBE) in 16 fractions over 4 weeks. Among them, seven patients who had locally advanced PC with bladder invasion were identified. Long-term androgen-deprivation therapy (ADT) was also administered to these patients. Adverse events were graded according to the Common Terminology Criteria for Adverse Event version 5.0. Results At the completion of our study, all the patients with cT4 PC were alive with a median follow-up period of 78 months. Grade 2 acute urinary disorders were observed in only one patient. Regarding late toxicities, only one patient developed grade 2 hematuria and urinary urgency. There was no grade 3 or worse toxicity, and gastrointestinal toxicity was not observed. Six (85.7%) patients had no recurrence or metastasis. One patient had biochemical and local failures 42 and 45 months after CIRT, respectively. However, the recurrent disease has been well controlled by salvage ADT. Conclusions Seven patients with locally advanced PC invading the bladder treated with CIRT were evaluated. Our findings seem to suggest positive safety and efficacy profiles for CIRT.

Open-label prospective study of safety and efficacy of glass-based Y-90 radioembolization for infiltrative HCC with PVT.

2014 ◽  
Vol 32 (3_suppl) ◽  
pp. 276-276
Author(s):  
Nima Kokabi ◽  
Juan C. Camacho ◽  
Minzhi Xing ◽  
John S. Kauh ◽  
Bassel F. El-Rayes ◽  
...  
Keyword(s):  
Prognostic Factors ◽  
Liver Toxicity ◽  
Univariate Analysis ◽  
Evaluation Criteria ◽  
Best Supportive Care ◽  
Open Label ◽  
Safety And Efficacy ◽  
Vein Thrombosis ◽  
Grade 3 ◽  
Bilirubin Toxicity

276 Background: Safety and efficacy of Yttrium-90 (Y90) therapy for infiltrative unresectable hepatocellular carcinoma (HCC) with portal vein thrombosis (PVT) require further evaluation. Methods: A prospective single center, open-label, single arm safety and efficacy study recruited patients with unresectable (Barcelona Liver Cancer Stage C) infiltrative HCC with PVT. Safety was assessed according to Common Terminology Criteria for Adverse Events v.3.0 at 1 week and monthly thereafter for 6 months post therapy. Efficacy was assessed by overall survival (OS) as primary endpoint. Tumor response was assessed by dynamic contrast MRI according to Response Evaluation Criteria in Solid Tumors (RECIST) and modified RECIST at 1, 3, and 6 months (secondary endpoint). To achieve 0.95 power (α=0.05) and predicting prolongation of mean OS by at least 50% over the best supportive care (4 months ± 2 months (SD)), the study was designed to recruit 30 patients. Survival analysis was performed using Kaplan-Meier estimation. Prognostic factors were tested using log-rank and univariate analysis. Results: Thirty (n=30) patients were enrolled and underwent Y90 therapy (median age 63). The median OS was 13 months (CI: 4.1-21.1 months). Six patients had transaminitis (70% grade 1, 30% grade 2) while 8 patients had biliary toxicity (50% grade 1, 10% grade 2, 40% grade 3). Grade 3 bilirubin toxicity occurred in the same 2 patients with grade 2 transaminase toxicity. Although all patients recovered from transient liver toxicities, grade ≥2 liver toxicity was found to be predictor of poor outcome with median OS of 3.6 months for patients with grade ≥2 toxicity vs. 13 months for those with grade 1 or no toxicity (p=0.004). Child-Pugh class B, INR ≥1.5, and grade ≥2 hepatobiliary toxicities were found to be poor prognostic factors by both log-rank and univariate analysis (p<0.05). Upon short-term imaging follow up (mean 34 days post Y90), 80% of patients were found to have complete (13%) or partial (67%) response according to targeted mRECIST criteria, with 93% stable disease according to targeted RECIST. Conclusions: In patients with unresectable infiltrative HCC and PVT, Y90 therapy is a viable and safe treatment option.

Capecitabine and oxaliplatin as induction and concomitant with radiotherapy in rectal cancer: A phase II study.

2011 ◽  
Vol 29 (4_suppl) ◽  
pp. 604-604
Author(s):  
J. A. Gutierrez ◽  
G. Martinez-Martinez ◽  
A. J. Silva ◽  
J. Gomez Rangel ◽  
M. Palmerin ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Performance Status ◽  
Locally Advanced ◽  
Pathologic Complete Response ◽  
Complete Response ◽  
Induction Treatment ◽  
Ecog Performance Status ◽  
Dermatologic Toxicity ◽  
Grade 3 ◽  
Experienced Grade

604 Background: Preoperative combined modality chemoradiation with fluoropyrimidine-based schedules is widely accepted as the current standard of care for localized rectal cancer. Current strategies have focused on intensifying the neoadjuvant systemic treatment to improve pCR. Methods: From January 2009 to January 2010, 18 patients with locally advanced rectal cancer (T3, any N, M0) were included according to Simon's design. Treatment was 2 cycles of capecitabine 1000 mg/m2 bid (D1-14) and oxaliplatin 85 mg/m2 (D1) every 3 weeks as induction followed by chemoradiation (45 Gy). During radiotherapy patients received 2 cycles of capecitabine 750 mg/m2 bid (D1-14) and oxaliplatin 85 mg/m2 (D1 and 8) every 3 weeks. Surgery was planned 5-10 weeks after completion of radiotherapy. The primary endpoint was pCR. Results: 18 patients were assessable for response. Median age was 55 y (41-65), 11 patients with ECOG performance status of 1 (61%), all 18 patients were staged as T3, 10 were staged N+ (56%). Of the 18 patients, 17 patients were given CRT and 13 patients (76%) underwent radical resection. Of the patients who did not underwent resection, 1 patient was considered unresectable at the time of surgery, 2 patients refused surgery because of clinical complete response and 1 patient experienced progressive disease to the spine after chemoradiation. During induction treatment 1 patient (6%) experienced grade 3-4 toxicity (diarrhea). During chemoradiation 1 patient (6%) experienced grade 3 diarrhea and nausea and 1 patient (6%) experienced grade 3 radio-induced dermatologic toxicity; overall grade 3-4 toxicity of 12%. No grade 4 toxicity or treatment related deaths were observed. Of the 13 patients who underwent resection, 12 patients (92%) had a complete resection (R0). Pathologic complete response rate was observed in 1 patient (6%) according to intent to treat. The study was closed after the first stage because it did not reach the minimum required number of pCR. Conclusions: Induction chemotherapy with capecitabine and oxaliplatin before chemoradiation is feasible. Given that we did not reach the prespecified pCR rate required to continue the trial, the study was closed after the first stage. No significant financial relationships to disclose.

Phase II study of bevacizumab and cetuximab as neoadjuvant treatment in locally advanced rectal cancer: A preliminary security report.

2011 ◽  
Vol 29 (4_suppl) ◽  
pp. 627-627 ◽  
Author(s):  
G. Elvira ◽  
L. Torrecillas ◽  
G. Cervantes ◽  
A. A. Erzao Valle Solis
Keyword(s):  
Rectal Cancer ◽  
Locally Advanced ◽  
Neoadjuvant Treatment ◽  
Advanced Rectal Cancer ◽  
Locally Advanced Rectal Cancer ◽  
External Beam Radiation ◽  
Induction Treatment ◽  
Second Phase ◽  
Beam Radiation ◽  
Grade 3

627 Background: Concurrent chemoradiotherapy is the standard treatment in locally advanced rectal cancer. Bevacizumab and cetuximab are accepted today in the treatment of metastatic colorrectal cancer. We evaluate the activity and security of these drugs in the neoadyuvante setting. Methods: Ten patients have been included so far. Treatment consists in a first phase with induction treatment with capecitabine 2,000 mg/m2 D1-14, oxaliplatin 130 mg/m2 and bevacizumab 7.5 mg/kg every 3 weeks for two cycles. In sequential form a second phase that consist in external beam radiation therapy that was given at 50.4 Gy in 28 sesions concurrently with capecitabine 1,300 mg/m2 /d continuous during radiotherapy with cetuximab 400 mg/m2 every two weeks in patients with k-ras wild type. Results: 10 patients completed induction treatment and eight patients completed the concurrent phase. As of today, two patients are still on treatment. At this point, four patients have been operated; three patients are still waiting for surgery, and one avoided surgery. During induction treatment the main toxicity was disesthesias in eight patients, four patient presented grade 2 emesis, two presented grade 2 altered liver function test, two had grade 2 hand foot syndrome. One patient presented grade 3 hemorrhage. During the second phase, eight patients received cetuximab and presented rash grade 1-2, diarrhea grade 1 in five patients, emesis grade 1 in four patients, anemia grade 2 in two patients, proctitis grade 2 in four patients, and grade 3 in one patient. From four patients who were operated two presented complete pathological response and two have tumor persistence. Conclusions: The combination of chemoradiation with bevacizumab and cetuximab seems to be secure with no increment in toxicity and those presented are acceptable and manageable. No significant financial relationships to disclose.

ABOUND.70+: Safety and efficacy of nab-paclitaxel/carboplatin (nab-P/C) in elderly patients (pts) with advanced non-small cell lung cancer (NSCLC).

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 9059-9059 ◽  
Author(s):  
Corey J. Langer ◽  
Eric C. Anderson ◽  
Robert M. Jotte ◽  
Jonathan Wade Goldman ◽  
Daniel Ernest Haggstrom ◽  
...  
Keyword(s):  
Primary Endpoint ◽  
Type I Error ◽  
Locally Advanced ◽  
Dose Intensity ◽  
Median Number ◽  
Phase Iii ◽  
Type I ◽  
Weekly Dose ◽  
Safety And Efficacy ◽  
Grade 3

9059 Background: Treatment (tx) of elderly pts with NSCLC is challenging. nab-P/C demonstrated efficacy in a subset of pts with NSCLC ≥ 70 y in a phase III trial. ABOUND.70+ was designed to determine whether a 1-week break can further improve tolerability of nab-P/C in pts ≥ 70 y with NSCLC. Safety and efficacy were evaluated and are reported. Methods: Pts ≥ 70 y with tx-naive locally advanced/metastatic NSCLC were randomized (1:1) nab-P 100 mg/m2 d 1, 8, 15 + C AUC 6 d 1 q3w (Arm A) or the same nab-P/C dose q3w followed by a 1-week break (Arm B). Primary endpoint: percentage of pts with either grade ≥ 2 peripheral neuropathy (PN) or grade ≥ 3 myelosuppression AEs. Key secondary endpoints: PFS, ORR, OS, for which statistical analyses do not control for type I error ( Pvalues unadjusted). Results: At interim evaluation, the primary endpoint was similar across arms, resulting in early closure of enrollment. In Arms A and B, 71 and 72 pts were randomized; median age was 76 and 75 y, majority of pts were male (57.7% vs 55.6%) and had ECOG PS 1 (70.4% vs 72.2%). There were no differences in histology across tx arms. See table for primary endpoint data. Median number of tx cycles for Arms A and B was 4.0 and 5.5, median cumulative nab-P dose was 875.0 and 1287.5 mg/m2, and median weekly dose intensity was 62.0 and 54.1 mg/m2. nab-P dose modifications (Arms A and B): ≥ 1 dose reduction in 64.7% and 58.6%, ≥ 1 dose delay in 58.8% and 48.6%, and ≥ 1 missed dose in 80.9% and 72.9%, respectively. Median PFS (Arms A and B) 3.9 vs 7.0 mo (HR 0.49; 95% CI, 0.30 - 0.79; P = 0.003), confirmed ORR 23.9% vs 40.3% ( P = 0.037), and median OS 15.2 vs 16.2 mo (HR 0.76; 95% CI, 0.46 - 1.26; P= 0.292). Conclusions: Incidence of grade ≥ 2 PN or grade ≥ 3 myelosuppression AEs was similar between the 2 nab-P/C schedules in pts ≥ 70 y with advanced NSCLC. There appears to be a signal of improvement in PFS and ORR observed in Arm B, potentially due to increased tx exposure. NCT02151149 Clinical trial information: NCT02151149. [Table: see text]

A multicenter phase II study of induction CT with FOLFOX-4 and cetuximab followed by RT and cetuximab in locally advanced esophageal cancer (LAEC)

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 4546-4546
Author(s):  
F. De Vita ◽  
M. Orditura ◽  
R. Innocente ◽  
L. Vecchione ◽  
C. Pinto ◽  
...  
Keyword(s):  
Response Rate ◽  
Locally Advanced ◽  
Growth Factor Receptor ◽  
Palliative Surgery ◽  
Pet Scan ◽  
Induction Treatment ◽  
Eligibility Criteria ◽  
Histopathological Response ◽  
Stage Design ◽  
Grade 3

4546 Background: Preoperative CRT improves the survival of pts with EC when compared with surgery alone. Epidermal growth factor receptor (EGFR) is overexpressed in 30–90% of EC and is associated with poor prognosis, providing the rationale for using the anti-EGFR monoclonal antibody cetuximab (C). The purpose of the study was to investigate the efficacy, toxicity and feasibility of C with FOLFOX- 4 regimen as induction CT followed by C and RT in pts with LAEC in a multicenter setting. Methods: Eligibility criteria: resectable, locally advanced (uT3 or uN1, T4 if deemed resectable) squamous cell carcinoma (SCC) or adenocarcinoma (AC) of the esophagus; staged by EUS, CT and PET scan; age 18–70y; PS <2; normal organ functions.All pts received induction treatment with C at a starting dose of 400 mg/m2 and further weekly infusion at a maintenance dose of 250 mg/m2 and 4 cycles of FOLFOX-4 every two weeks. Post-induction EUS and CT scans were performed, while a PET scan was repeated early before second cycle of CT: pts without PD were given daily RT (180cGy fractions to 5040cGy) with concurrent weekly C. Post RT, EUS plus biopsies, CT scan and PET were performed. At wk 18, pts without PD had esophagectomy. Simons two stage design was used. Primary endpoint was histopathological response rate. Results: Up to December 2008, 40 pts, 30 men, were enrolled from 4 institutions; median age 59 y (35–70y); AC 12; SCC 28; stage II 15, stage III 25 pts. At this time 32/40 pts were evaluable. The most frequent grade 3/4 toxicity of chemoradiotherapy were skin (32%),neutropenia (29%) and esophagitis (9%); 10 pts had no resection (9 progressive disease,1 patient's refusal). Of 22 operated pts, 17 pts (77%) had RO-resection, 5 pts had palliative surgery.2 pts died due to complications after surgery (1 after > 30 days). The pathological response rate was 68 %, with a complete histopathological remission recorded in 6 pts (27%);17 pts (53%) are still alive without residual or recurrent disease. Conclusions: The current findings suggest the feasibility of incorporating cetuximab into a preoperative regimen for LAEC pts and an encouraging antineoplastic activity with 68% histopathological responders. No significant financial relationships to disclose.

MO19390 (SAiL): Safety and efficacy of first-line bevacizumab (Bv)-based therapy in advanced non-small cell lung cancer (NSCLC)

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 8043-8043 ◽  
Author(s):  
L. Crino ◽  
J. Mezger ◽  
F. Griesinger ◽  
C. Zhou ◽  
M. M. Reck
Keyword(s):  
Adverse Events ◽  
Disease Progression ◽  
Special Interest ◽  
Locally Advanced ◽  
Real Life ◽  
First Line ◽  
Safety And Efficacy ◽  
Grade 3 ◽  
Ecog Ps ◽  
Experienced Grade

8043 Background: MO19390 (SAiL) is a single-arm, multicenter, international trial evaluating the safety and efficacy of first-line Bv in combination with a range of chemotherapy regimens in over 2,000 patients (pts). Methods: Primary endpoint was safety; secondary endpoints included time to disease progression (TTP) and overall survival (OS). Pts with untreated locally advanced, metastatic or recurrent non-squamous NSCLC (ECOG PS 0–2) received Bv (7.5 or 15mg/kg) with standard chemotherapy for up to six cycles, then non-progressors proceeded to receive Bv until disease progression. Results: This analysis (data cut-off July 2008) was based on 2,008 pts with a median age of 59. Pts (%) were: male 60.1; stage IIIB/IV 19.5/80.5 (no data 3 pts); adenocarcinoma/large cell/other 85.8/7.1/7.1; ECOG PS 0/1/2 38.1/56.1/5.8. Pts received a median of 6 Bv cycles and 4 chemotherapy cycles. 26.7% of pts experienced grade ≥3 serious adverse events (SAEs); 8.3% of pts experienced grade ≥3 SAEs related to Bv. Adverse events (AEs) of special interest (all grades) included bleeding (27.6%), hypertension (19.3%), proteinuria (14.6%), thromboembolism (8.6%), CHF (2.9%) and GI perforation (1.2%). The incidence of AEs of special interest (all grades) was comparable across the various types of chemotherapy regimens: carboplatin doublets (50.6%)/cisplatin doublets (49.9%)/non-platinum doublets (41.7%)/monotherapy (37.5%). No new safety signals were reported. Trial data were not deemed mature enough to provide efficacy results. Conclusions: SAiL confirms that Bv-based therapy has a well-established and manageable safety profile. Clinical outcomes obtained in this real-life population are consistent with those seen in the pivotal trials of bevacizumab (Avastin) in NSCLC (E4599 and AVAiL), and compare favorably with historical data. Updated efficacy results for 2,147 pts will be presented, based upon an additional 5 months’ follow-up. [Table: see text]

First results of induction chemotherapy with cisplatin, docetaxel, and capecitabine for the treatment of nasopharyngeal carcinoma

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 6045-6045
Author(s):  
Y. Beldjilali ◽  
K. A. Benhadji ◽  
A. Boukerche ◽  
H. Khellafi ◽  
A. Abdelaoui ◽  
...  
Keyword(s):  
Nasopharyngeal Carcinoma ◽  
Induction Chemotherapy ◽  
Tumor Response ◽  
Performance Status ◽  
Locally Advanced ◽  
High Response Rate ◽  
Induction Treatment ◽  
Ecog Performance Status ◽  
P 75 ◽  
Grade 3

6045 Background: The purpose of this phase II study is to assess a new induction chemotherapy regimen combining cisplatin (P), docetaxel (T), and capecitabine (X) in advanced nasopharyngeal carcinoma. Methods: Previously untreated patients (pts) with histological diagnosed locally advanced nasopharyngeal carcinoma (stages III, IVA, and IVB UICC 2002) received induction chemotherapy associating P 75 mg/m2, T 75 mg/m2, both on day 1 and X 1,000 mg/m2/d days 1–14. Cycles were repeated every 3 weeks. A total of 4 cycles was planned for each patient. Induction chemotherapy was followed by concurrent chemo-radiotherapy: P 75 mg/m2 days 1, 22, 42 and radiotherapy (65–70 Gy) 4 to 6 weeks after the fourth cycle of induction treatment. Primary end point was tumor response of the induction regimen. Pts were evaluated according to RECIST criteria by clinical examination and CT scan of the nasopharynx. Results: 40 pts (26 male and 14 female) were enrolled. Median age was 40 years (range 18–56), ECOG performance status was 0–1 in all pts. 30 pts (75%) had an undifferentiated carcinoma of nasopharyngeal type (UCNT) and 10 pts (25%) a poorly differentiated nasopharyngeal carcinoma. 5 pts had stage III disease, 20 pts stage IVA disease and 15 pts stage IVB. Toxicity and tumor response were assessable in 40 pts. After 160 cycles, grade 3–4 toxicities (NCI-CTC 3.0) were: neutropenia (11 %), anemia (10.5%), nausea and vomiting (28%), diarrhea (8%), mucositis (3%), reversible alopecia (100%), and fatigue (10%). No febrile neutropenia was noted. 2 pts had grade 3 renal toxicity and only one patient had hand-foot syndrome (grade 3). Response rates for the 40 pts were: complete response 48%, partial response 40%, stable disease 4%, and progressive disease 8%. Conclusions: PTX induction chemotherapy resulted on a high response rate with manageable toxicity. Outcome of patients after chemoradiotherapy is awaited to evaluate the effectiveness of this new treatment modality. No significant financial relationships to disclose.

Safety and efficacy of durvalumab following multimodality therapy for locally advanced esophageal and GEJ adenocarcinoma: Two-year follow-up results from Big Ten Cancer Research Consortium study.

2020 ◽  
Vol 38 (4_suppl) ◽  
pp. 404-404 ◽  
Author(s):  
Hirva Mamdani ◽  
Bryan J. Schneider ◽  
Pashtoon Murtaza Kasi ◽  
Laith I. Abushahin ◽  
Thomas J. Birdas ◽  
...  
Keyword(s):  
Residual Disease ◽  
Checkpoint Inhibitors ◽  
Locally Advanced ◽  
Predictive Biomarkers ◽  
R0 Resection ◽  
Trimodality Therapy ◽  
Surgical Specimen ◽  
Safety And Efficacy ◽  
Grade 3

404 Background: Concurrent chemoradiation(CRT) followed by esophagectomy is a standard of care for locally advanced esophageal(LA-EAC) and GEJ adenocarcinoma. Approximately 50% of patients(pts) experience disease relapse within the 1st yr after treatment(tx) completion. No adjuvant tx has been shown to improve survival in these pts. Immune checkpoint inhibitors have activity in metastatic PD-L1 positive EAC. Preclinical studies have shown radiation +/- chemotherapy upregulate PD-1/PD-L1 pathway. Methods: We conducted a phase II trial evaluating safety and efficacy of durvalumab(durva) in pts with LA-EAC and GEJ adenocarcinoma who have residual disease in surgical specimen after neoadjuvant CRT and R0 resection. Pts received durva 1500mg IV every 4 weeks for up to 1yr. Results: 24 pts were enrolled from 4/2016-1/2018(median age: 60yrs (range, 43-70). 18 received carbo/paclitaxel and 6 received cis/5-FU concurrently with radiation. Staging at diagnosis: T2N0(n = 3, 12.5%), T2N2(n = 3, 12.5%),T3N0(n = 6, 25%), T3N1(n = 6, 25%), T3N2(n = 4, 17%), T3N3(n = 1, 4%), T3Nx(n = 1, 4%).19 pts(79%) had positive lymph nodes(LNs) at the time of surgery following CRT. 12 pts completed 1yr of tx, 12 came off tx because of relapse(6), AEs(5), and consent withdrawal(1). Most common AEs were fatigue(n = 8, 33.3%) and nausea(n = 6, 25%). 3pts (12.5%) developed grade 3 irAEs: pneumonitis(1), hepatitis(1), colitis(1). At median follow up of 21.9mo(range, 1.7-23.9mo), 11 pts have relapsed: 9 distant and 2 locoregional. Two of 3 pts with grade 3 irAEs are alive and disease free at 17 and 23 mo respectively. 1-yr RFS and OS were 79.2% and 95.5%, respectively. RFS at 26 mo was 20.6%. Overall mOS and mOS after relapse were 28.1mo(range, 22.9-28.1) and 11.1 mo(range, 0.1-11.3mo) respectively. The study was expanded to enroll 14 additional pts who are currently undergoing tx. Conclusions: Adjuvant durvalumab following trimodality therapy for LA-EAC and GEJ adenocarcinoma is safe with improvement in 1-yr RFS to 79.2% compared to historical rate of 50%. RFS was 20.6% at 26 months. Evaluation of predictive biomarkers of RFS with durva is underway. Clinical trial information: NCT02639065.

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