Enhanced pathologic tumor response with two cycles of neoadjuvant pembrolizumab in surgically resectable, locally advanced HPV-negative head and neck squamous cell carcinoma (HNSCC).

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 6008-6008
Author(s):  
Ravindra Uppaluri ◽  
Rebecca Chernock ◽  
Mena Mansour ◽  
Ryan Jackson ◽  
Jason Rich ◽  
...  
Keyword(s):  
Primary Endpoint ◽  
Tumor Response ◽  
Clinical Stage ◽  
Locally Advanced ◽  
Fold Increase ◽  
Pathologic Response ◽  
Smoking History ◽  
Blood Collection ◽  
Serious Adverse Events ◽  
Phase 2 Trial

6008 Background: We reported that one cycle of neoadjuvant pembrolizumab induced pathologic tumor response in >10% (pTR-any) and in >50% (pTR-2) of the resection bed in 44% and 22% of patients (pts) with surgically resectable HPV-negative, Stage III/IV HNSCC ( Clin Cancer Res 2020). We hypothesized that two cycles of neoadjuvant pembrolizumab would induce pTR-2 in 50% of pts. Increasing the pathologic response rate may favorably impact clinical outcomes. Methods: Multi-institutional phase 2 trial where pts with locally advanced, HPV-negative HNSCC received two cycles of pembrolizumab (200 mg), given 42 and 21 days prior to surgery. Resected tumor was analyzed by two independent pathologists for pTR (tumor necrosis and/or giant cell/histiocytic reaction to keratinous debris) in the resection bed (primary tumor and/or lymph nodes). Additional definitions: pTR-1 (>10-49%) and major pathologic response ( > 90%). The primary endpoint was pTR-2. A sample size of 26 pts was needed to detect a significantly higher pTR-2 rate of 50%, with 80% power using a one-sided alpha level of 0.05. Pts were followed for serious adverse events (AEs) for 30 days after surgery and for AEs of clinical interest for 90 days following the last dose of pembrolizumab. Pts underwent baseline blood collection and tumor biopsies to match with blood and surgical specimens obtained post-pembrolizumab. Planned correlatives included PD-L1 expression, immune function, and molecular signatures of activation in the pre- and post-treatment blood and tumor tissue. Results: Characteristics of 29 enrolled and treated pts were median age 62 (30-82) yrs, smoking history 62% (18 pts); clinical stage T2 (n = 6), T3 (n = 5), T4 (n = 18) and N0/1 (n = 17), N2 (n = 12). All treated patients received two cycles of neoadjuvant pembrolizumab, which was tolerated well with only one (3%) grade 3 AE (rash) and no grade 4 AEs. The primary endpoint was evaluable in 25 pts, and not evaluable in 4 pts (one pt withdrew before surgery and in three pts, pTR review was pending). pTR-2 occurred in 44% (11 of 25 pts), and 4 (16%) of these pts had a major pathologic response including 1 (4%) pathologic CR at the primary site. Conclusions: Two (vs one) cycles of neoadjuvant pembrolizumab resulted in a two-fold increase in the frequency of pTR-2 (44% vs 22%). These data imply that the frequency of pTR to neoadjuvant pembrolizumab can be improved by increasing the number of cycles and the treatment interval. Clinical trial information: NCT02296684.

Chemotherapy first, followed by chemoradiation (CRT) and then surgery, in the management of locally advanced rectal cancer (LARC).

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 3605-3605
Author(s):  
Andrea Cercek ◽  
Karyn A. Goodman ◽  
Carla Hajj ◽  
Emily Weisberger ◽  
Neil Howard Segal ◽  
...  
Keyword(s):  
Clinical Response ◽  
Tumor Response ◽  
Tumor Regression ◽  
Clinical Stage ◽  
Locally Advanced ◽  
Operative Management ◽  
High Rate ◽  
Complete Clinical Response ◽  
Response To Chemotherapy ◽  
Non Operative Management

3605 Background: Standard pre-op CRT and post-op chemo for LARC delays the start of optimal systemic therapy by 18-22 weeks. To more promptly address micrometastases that could lead to distant failure, and supported by evidence of excellent primary tumor response to FOLFOX, we began offering FOLFOX as initial treatment for patients (pts) with high-risk LARC. More recently, we have begun offering all planned FOLFOX prior to CRT and surgery. Methods: We obtained an IRB waiver to review records of all clinical stage II/III RC pts treated with initial FOLFOX followed by CRT and total mesorectal excision (TME) at our institution between 2007 and 2012. Of approximately 300 rectal pts treated with CMT, 61 received some or all of their planned FOLFOX as initial therapy. Results: The median age of these 61 pts was 52 years, 54% male. At diagnosis, 84% had T3N1-2 or T4N0-1 tumors and 16% had T3N0 tumors. Of these, 57 received induction FOLFOX (median 7 cycles) then received pre-op CRT, while 4 pts achieved an excellent response to chemotherapy alone, declined CRT, and went directly to TME. Twelve pts did not undergo surgery; 9 had a complete clinical response and elected to be managed non-operatively; 1 refused recommended surgery despite incomplete tumor regression, 1 had surgery deferred due to comorbidities, and 1 developed distant metastatic disease prior to planned surgery. Of the 61 patients, 19 (31%) had either a pathCR (14) or a complete clinical response (5) leading to non-operative management. Of the 49 pts who underwent TME, all had R0 resections and 23 (47%) had tumor response >90%, including 13 (27%) with pathCR. Of the 28 patients who received all 8 cycles of initial FOLFOX, 8 achieved a pathCR (29%) and 3 achieved a complete clinical responses (11%), managed non-operatively. All patients completed therapy as planned. There were no SAEs requiring delay in treatment during either FOLFOX or CMT. Conclusions: FOLFOX before CRT results in substantial tumor regression, a high rate of delivery of all planned therapy, and a substantial rate of pathCRs. Chemo and CMT before planned TME provides a favorable opportunity for consideration of non-operative management.

Transoral robotic surgical resection followed by randomization to low- or standard-dose IMRT in resectable p16+ locally advanced oropharynx cancer: A trial of the ECOG-ACRIN Cancer Research Group (E3311).

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 6500-6500 ◽  
Author(s):  
Robert L. Ferris ◽  
Yael Flamand ◽  
Gregory S. Weinstein ◽  
Shuli Li ◽  
Harry Quon ◽  
...  
Keyword(s):  
Primary Endpoint ◽  
Standard Dose ◽  
Locally Advanced ◽  
Operative Therapy ◽  
Phase Iii ◽  
Smoking History ◽  
Transoral Surgery ◽  
Intermediate Risk ◽  
Oropharynx Cancer ◽  
Transoral Resection

6500 Background: ECOG-ACRIN 3311 examines reduced postoperative therapy in patients with “intermediate risk” p16+ oropharynx cancer (OPC) undergoing primary transoral surgical management. We report the primary endpoint of 2-year progression free survival (PFS) for patients randomized to 50Gy vs 60Gy without chemotherapy. Methods: Between December 2013 and July 2017, 82 credentialed surgeons performed transoral resection (TOS) for 519 OPC patients (cT1-2 stage III/IV AJCC7 without matted neck nodes); post-operative management was determined by pathologically assessed risk. Among 353 eligible and treated patients, Arm A enrolled 10% (N=37) for clear margins, 0-1 nodes, no extranodal extension (ENE)), Arms B (50Gy, N=102) or C (60Gy, N=104) randomized 58%, for clear/close margins, 2-4 + nodes, or ENE ≤1mm, while Arm D (N=110, 60-66Gy plus weekly cisplatin, 40 mg/m2, positive margin with any T stage, >4 + nodes, or >1mm ENE) enrolled 31%. Arm D assignment was based on >1mm ENE (76%), > 4 nodes (27%), and/or positive margins (11%). Intermediate-risk patients were stratified by smoking history (>10 pk-yr). Of the 80 pts (15%) deemed ineligible, 28 had scans/labs not done per protocol, however treatment arm distribution for all patients mirrored that for the 353 pts eligible and treated. Results: Median follow-up was 31.8 months. 2 yr PFS for Arms A, B and C were 93.9% (90% CI=87.3%, 100%), 95.0% (90% CI=91.4%, 98.6%) and 95.9% (90% CI=92.6%, 99.3%) respectively, while Arm D was 90.5% (90% CI=85.9%, 95.3%). The regimen of TOS + low-dose radiation is considered worthy of further study, since the primary endpoint of the upper bound of the 90% CI (in the intermediate risk group) exceeding 85% was met. Of 17 progression events, 7 were locoregional. There were 10 distant recurrences: Arm A=1, Arm B=2, Arm C=4, Arm D=3. Grade III/IV treatment-related AE rates were 15%/2% during surgery, 13%/2% for Arm B and 25%/0% for Arm C. There were 2 treatment-related deaths (one surgical and one Arm D). Conclusions: Transoral resection of p16+ OPC is safe and results in good oncologic outcome, presenting a promising deintensification approach. For patients with low-risk disease, 2-yr PFS is favorable without post-operative therapy. For those with uninvolved surgical margins, <5 involved nodes, and minimal (<1mm) ENE, reduced dose postoperative RT without chemotherapy appears sufficient. Transoral surgery plus 50Gy should be compared to optimal non-surgical therapy in a phase III trial. Clinical trial information: NCT01898494 .

scholarly journals Biochemical Tumor Marker Status and Its Role in Treatment Response in Patients Who Received High-Specific-Activity I-131 MIBG in Advanced Pheochromocytoma and Paraganglioma (PPGL): Results From a Pivotal Phase 2 Clinical Trial

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A164-A165
Author(s):  
Camilo Jimenez ◽  
Bennett B Chin ◽  
Richard A Noto ◽  
Richard B Noto ◽  
Joseph S Dillon ◽  
...  
Keyword(s):  
Tumor Marker ◽  
Correlation Coefficient ◽  
Primary Endpoint ◽  
Antihypertensive Medication ◽  
Tumor Response ◽  
Specific Activity ◽  
Locally Advanced ◽  
High Specific Activity ◽  
Objective Tumor Response ◽  
Biomarker Response

Abstract Background: High-specific-activity iodine-131 meta-iodobenzylguanidine (HSA I-131 MIBG; AZEDRA®) has been approved for the treatment of adult and pediatric patients (pts) 12 years and older with iobenguane scan positive, unresectable, locally advanced or metastatic PPGL who require systemic anticancer therapy. We have previously presented data showing improved biomarker responses in pts treated with HSA I-131 MIBG. Here we report the impact of biomarker status on the study primary endpoint and objective tumor response. Methods: Pts with iobenguane-avid PPGL who were ineligible for surgery, failed prior therapy or not candidates for chemotherapy, and on a stable antihypertensive medication regimen were treated. Pts received up to two therapeutic doses, each at ~18.5 GBq (or 296 MBq/kg for pts ≤62.5 kg), administered ~90 days apart. Biomarkers were analyzed at baseline and over a 12-month efficacy period. Confirmed biochemical responses (at least ≥ 50% decrease in abnormal tumor marker value for all hypersecreted biomarkers) required subsequent responses to be identical to or better compared with the previous assessment. The primary endpoint was clinical benefit, defined as the proportion of pts with at least 50% reduction of all antihypertensive medication(s) for ≥6 months beginning during the efficacy period. The secondary endpoint, confirmed objective tumor response by RECIST, was also evaluated. Results: 68 pts received at least one therapeutic dose of HSA I-131 MIBG. For all pts with hypersecretory tumors (with a baseline biochemical marker level of ≥1.5× ULN) (n=60), a comparison of biomarker response with antihypertensive therapy yielded a correlation coefficient of 0.35 (P = 0.006; Fisher exact P = 0.012). For pts with norepinephrine only-hypersecreting tumors (n=31), a correlation coefficient of 0.47 (P = 0.008; Fisher exact P = 0.015) was observed. The overall biomarker response also correlated with objective tumor response (n=55) yielding a correlation coefficient of 0.36 (P = 0.007; Fisher exact P = 0.012) for all pts with hypersecreted biomarkers. Pts who were not biochemical hypersecretors for any biomarker (n=6) had only one responder for the primary endpoint and no objective tumor responses. Conclusions: The biomarker data from this study establish a moderate but statistically significant correlation between biomarker response following treatment with HSA I-131 MIBG and objective tumor response and durable reduction of antihypertensive therapy. This correlation was improved with norepinephrine only-hypersecreting tumors in pts with unresectable, locally advanced or metastatic PPGL.

A phase 2 trial of talimogene laherparepvec (TVEC) in combination with neoadjuvant chemotherapy for the treatment of nonmetastatic triple-negative breast cancer.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 578-578
Author(s):  
Hatem Hussein Soliman ◽  
Hyo S. Han ◽  
Deanna Hogue ◽  
Blaise Mooney ◽  
Ricardo L Costa ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Primary Endpoint ◽  
Survival Data ◽  
Clinical Stage ◽  
Stage Ii ◽  
Type I ◽  
Phase 2 ◽  
Immune Correlates ◽  
Phase 2 Trial

578 Background: TVEC is a modified oncolytic herpes simplex 1 (HSV1) virus currently FDA approved for the treatment of unresectable cutaneous and nodal melanoma. TVEC is designed to preferentially lyse tumor cells over normal tissue to release tumor associated antigens, produces GM-CSF to activate dendritic cells, and stimulates T cells to infiltrate the tumor (TILs). TILs in breast cancer are associated with better response to neoadjuvant chemotherapy (NAC), so we hypothesized that intratumoral TVEC may enhance response to NAC. We report results of a phase 2 trial combining NAC with TVEC in stage 2-3 TNBC. Methods: Stage II-III TNBC pts (N = 37) were to be enrolled into a single arm, optimal Simon 2 stage phase 2 trial with TVEC (10^6 PFU 1st dose then 10^8 PFU x 4 doses) weeks 1,4,6,8,10 + weekly paclitaxel (80mg/m2) IV x 12, followed by dose dense AC (doxorubicin/cyclophosphamide 60/600 mg/m2) IV q2weeks x 4 alone given preoperatively. Primary endpoint was residual cancer burden 0 rate (RCB0). Trial meets primary endpoint with ≥15 RCB0 responses out of 37 evaluable pts, assuming p1 = 45% vs. p0 = 30% with one sided type I error rate at 0.10 and power at 70%. Results: Forty pts were enrolled at Moffitt (5/2018 – 4/2020) and evaluable for safety with 3 pts non-evaluable for efficacy due to incomplete treatment. Study demographics: median age 49 (27-66), 67.5% White, 10% Black, 15% Hispanic, clinical stage II 83% and III 17%, node + 42%. The RCB0 rate = 16/37 (43%, 95% CI 27-61%) and additional 9 pts with RCB-1 (RCB0/1 rate 68%, 95% CI 50-82%). Toxicities did not differ significantly from expected NAC toxicities except for increased brief G1-2 fevers, chills, injection site pains. Four pts had G2-3 thromboembolic events (10%) slightly greater than expected 6% rate on NAC. Conclusions: Addition of TVEC to NAC increased RCB0 rates with manageable toxicities and warrants additional investigation in TNBC. Immune correlates and updated survival data will be presented at the meeting. Clinical trial information: NCT02779855.

Preoperative fluorouracil (FU)-based chemoradiation with and without weekly oxaliplatin in locally advanced rectal cancer: Pathologic response analysis of the Studio Terapia Adiuvante Retto (STAR)-01 randomized phase III trial

2009 ◽  
Vol 27 (18_suppl) ◽  
pp. CRA4008-CRA4008 ◽  
Author(s):  
C. Aschele ◽  
C. Pinto ◽  
S. Cordio ◽  
G. Rosati ◽  
A. Tagliagambe ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Tumor Response ◽  
Anal Verge ◽  
Locally Advanced ◽  
Advanced Rectal Cancer ◽  
Locally Advanced Rectal Cancer ◽  
Pathologic Response ◽  
Phase Iii ◽  
Local Tumor ◽  
Phase Iii Trial

CRA4008 Background: Oxaliplatin (OXA) enhances the efficacy of FU-based chemotherapy in colon cancer. This randomized phase III trial investigated the effect of adding OXA to preoperative (preop) FU-based pelvic chemoradiation (CRT) in patients (pts) with locally-advanced rectal cancer. Methods: Eligibility required a resectable, biopsy-proven rectal adenocarcinoma within 12 cm from the anal verge with radiological evidence of perirectal fat or lymphnode involvement. Randomization was between infused FU (225 mg/msq/day) concomitant to external-beam pelvic radiation (50.4 Gy in 28 daily fractions) (arm A) or the same regimen + weekly OXA (60 mg/msq × 6) (Arm B). Surgery was scheduled 6–8 weeks after completing CRT. Overall survival was the primary endpoint. A protocol-planned analysis of local tumor response to preop treatment (secondary end-point) is the object of this report. Results: 747 pts from 41 Italian centers were randomized between 12/2003 and 8/2008 (arm A/B: 379/368). Pretreatment characteristics in arm A/B: median age 63/62 years; male:female 2:1; median distance from anal verge 6 cm; T4 16/14%, N+ 63/65%. Overall grade 3–4 toxicity rates on treated pts (mainly diarrhoea) were 8% and 24% (arm A/B, p<0.001). 96/90% of pts (arm A/B) received > 90% of the planned RT. 82% of Arm B pts had > 5 oxa courses. 358/342 pts (arm A/B) had surgery at a median of 52/53 days from the end of CRT, 14 pts in each arm were not operated (progression 8, death 5, other/unknown 15) and surgery data are not yet available for 19 pts. Pathologic response data analyzed on the randomized population are reported in the table . Conclusions: The addition of weekly OXA to standard FU-based preop CRT significantly increases toxicity without affecting local tumor response. The reduced pathologic M+ rate suggests a potential effect on distant micrometastases. Longer follow-up is needed to assess the impact on efficacy endpoints. [Table: see text] No significant financial relationships to disclose.

Multicenter prospective phase II trial of neoadjuvant (neo) dose dense gemcitabine and cisplatin (DD-GC) in patients (pts) with muscle-invasive bladder cancer (MIBC).

2016 ◽  
Vol 34 (2_suppl) ◽  
pp. 436-436 ◽  
Author(s):  
Arjun Vasant Balar ◽  
Gopa Iyer ◽  
Matthew I. Milowsky ◽  
William C. Huang ◽  
Michael Woods ◽  
...  
Keyword(s):  
Primary Endpoint ◽  
Clinical Stage ◽  
Optimal Dose ◽  
Pathologic Response ◽  
Metastatic Setting ◽  
Prospective Phase ◽  
Muscle Invasive ◽  
Dose Dense ◽  
Ischemic Attack ◽  
Dose Modifications

436 Background: Cisplatin-based chemotherapy before radical cystectomy (RC) improves survival in pts with MIBC. DD-GC therapy is active in the metastatic setting [6 cycles (cy), 18 months median survival; Bamias et al, 2012)] and as neo therapy (3 cy, 44% ≤ pT1 rate; Plimack et al, 2014), but the optimal dose and number of cy of neo therapy has not been defined. We prospectively evaluated the activity and safety of 6 cy of neo DD-GC over 12 weeks in MIBC. Methods: Pts with T2-4aN0 disease received six 14-day cy of DD-GC as follows: G 2500 mg/m2 day 1, C 35 mg/m2 days 1 and 2, pegfilgrastim day 3. RC with bilateral pelvic lymph node dissection was planned within 8 weeks of DD-GC completion, regardless of clinical response. The primary endpoint was pathologic response ( ≤ pT1) rate ≥ 55% (exact Binomial one-sided test). Pts not undergoing RC were deemed non-responders regardless of clinical stage after DD-GC. Pts receiving < 3 cy were inevaluable and replaced. All pts were evaluable for toxicity. Results: 49 pts (40 male) were enrolled. Median age was 64 (range: 37-78). Clinical stage was T2N0 (32 pts), T3N0 (12 pts), and T4aN0 (5 pts). Toxicities resulting in cy delay and/or dose modifications included thrombocytopenia (9 pts), renal insufficiency (5 pts), vascular access complication (2 pts), ototoxicity (1 pt), significant urinary symptoms (1 pt), and transient ischemic attack (1 pt). Three pts are inevaluable for the primary endpoint ( < 3 cy). As of 9/7/15, 2 pts are pending RC. Of the 44 pts evaluable for response to date, 31 completed 6 cy of DD-GC, 6 pts completed 5, 3 pts completed 4, and 4 pts completed 3 (median: 6 cy). The median time to RC was 46 days. Four of 44 pts did not undergo RC (consent withdrawal, pt refusal, disease progression prior to RC, death from other causes). Trial accrual has closed with completion of clinical and pathologic data expected by 11/1/15. Of 40 pts with RC pathology available to date, 24 (60%) were ≤ pT1 and 7 (18%) were pT0. Conclusions: Six cy of DD-GC is an active well-tolerated neo chemotherapy regimen in pts with MIBC. The pathologic response rate is encouraging. Thrombocytopenia was the most common toxicity resulting in cy delays/dose modifications. Clinical trial information: NCT01589094.

Interim safety analysis of the DANTE trial: Perioperative atezolizumab in combination with FLOT versus FLOT alone in patients with resectable esophagogastric adenocarcinoma—A randomized, open-label phase II trial of the German Gastric Group at the AIO and SAKK.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 4549-4549
Author(s):  
Nils Homann ◽  
Sylvie Lorenzen ◽  
Michael Schenk ◽  
Peter C. Thuss-Patience ◽  
Eray Goekkurt ◽  
...  
Keyword(s):  
Adverse Events ◽  
Disease Progression ◽  
Phase Ii ◽  
Phase Ii Trial ◽  
Clinical Stage ◽  
Locally Advanced ◽  
Safety Analysis ◽  
Open Label ◽  
Serious Adverse Events ◽  
Open Label Phase

4549 Background: The DANTE study evaluates atezolizumab in the perioperative treatment of locally advanced, potentially resectable gastric or GEJ adenocarcinoma in combination with perioperative FLOT. Here, we report the protocol-defined interim safety analysis. Methods: DANTE is a multinational, prospective, multicenter, randomized, investigator-initiated, open label phase II trial. Patients (pts) with locally advanced, potentially resectable adenocarcinoma of the stomach and GEJ (≥cT2 and/or N-positive) without distant metastases are enrolled. Pts are randomized 1:1 to 4 pre-operative 2-week cycles of FLOT followed by surgery and 4 additional cycles of FLOT plus atezolizumab at 840 mg every 2 weeks, followed by a total of 8 additional cycles of atezolizumab at 1200 mg every 3 weeks as monotherapy (arm A) or FLOT alone (arm B). Primary endpoint is time to disease progression or relapse after surgery (PFS/DFS). Results: Recruitment started in Sep 2018; by Feb 2020, a total of 175 pts have been randomized. This analysis is based on the first 40 pts (20 pts in each arm). The pts had a median age of 62 y and 75% of pts had an ECOG PS of 0 in both arms. The cohort was well balanced in terms of tumor location and clinical stage. 5% of the 40 patients (overall 7.4% of 175 pts enrolled) showed microsatellite instability. 90% of pts enrolled completed all pre-operative cycles in each arm. Total number of adverse events with relation to study treatment was 154 in arm A and 148 in arm B. Total number of serious adverse events (SAE; related or not) was 16 in Arm A and 14 in arm B. 20% of pts in each arm had an SAE due to perioperative morbidity. No surgical mortality was observed. 18 and 19 pts proceeded to operation in arms A and B, respectively. Premature treatment discontinuation occurred in 2 pts in each arm: disease progression (1) and deterioration of general health condition (1) in arm A; and pts’ wish (1) and death (1) in arm B. Median hospitalization time was 15 days in arm A and 16 days in arm B. Conclusions: Perioperative atezolizumab plus FLOT is feasible and safe. The study continues recruitment. Clinical trial information: NCT03421288 .

Neoadjuvant nivolumab (N) plus weekly carboplatin (C) and paclitaxel (P) in resectable locally advanced head and neck cancer.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 6583-6583
Author(s):  
Ralph Zinner ◽  
Jennifer M Johnson ◽  
Madalina Tuluc ◽  
Joseph M. Curry ◽  
Adam Luginbuhl ◽  
...  
Keyword(s):  
Head And Neck ◽  
Primary Endpoint ◽  
Locally Advanced ◽  
Pathologic Response ◽  
Primary Site ◽  
Stage Iii ◽  
Unknown Primary ◽  
Scanning System ◽  
Viable Tumor ◽  
Platinum Based Chemotherapy

6583 Background: Despite multimodality standard therapy, patients (pts) with resectable locally advanced squamous cell carcinoma of the head and neck (LA SCCHN) are at high risk for recurrence. Pts with pathologic complete response (pCR) or major pathologic response (MPR) to neoadjuvant chemotherapy have improved overall survival. PD-1 checkpoint inhibitors are approved in combination with platinum-based chemotherapy in the 1st-line treatment of recurrent/metastatic SCCHN. We hypothesize the addition of N to wkly carboplatin C and P will increase the pCR rate at the primary site compared to historical controls. Methods: This is an investigator-initiated trial for pts with newly diagnosed (AJCC 8th) stage III-IV HPV- (oral cavity (OC), oropharynx (OP), hypopharynx (HP), and larynx (L) or stage II-III HPV+ OP SCCHN without distant metastasis who are surgical candidates. Neoadjuvant chemo starting d1 is C AUC 2 IV wkly x 6 plus P 100 mg/m2 IV wkly x 6 plus N 240 mg IV q 2 wks x 3 with surgery on wk 8. The primary endpoint is pCR at the primary site. To estimate pathologic response, the resected pathology specimens are cut >1 section/cm. Using the Aperio Digital scanning system, slides are imaged, and then annotated by at least 2 pathologists for viable tumor vs. treatment effect with areas automatically calculated to yield the percentage of viable tumor. Our primary endpoint will be reached if 11/37 planned pts have a pCR at the primary site. Results: From 11/17-12/19, 27 pts received the study regimen and had surgery (1/27 had an unknown primary; thus, inevaluable for the primary endpoint). Of 27 pts, median age was 59 (46-83), women 31%, HPV+ 15%, OC 73%, OP 19%, HP 7%, L 4%; stage III 33%, stage IVA 67%. Gd 3 toxicities were in 37% pts; 1 pt febrile neutropenia, 3pts anemia, 1pt diarrhea, 1pt cellulitis and 1pt rash. Four pts had gd 3-4 neutropenia. Dose reductions were in 2 pts, and 4 pts had 1 wkly dose dropped. All 27 pts went to surgery, none with PD by CT; all with negative margins. One pt died with rapid recurrence; no other recurrences (median f/u 13 mos). Our primary endpoint was met; 11/26 (42%) pts (excluding pt with unknown primary) had a pCR at the primary site. 9/23 (39%) HPV- pts, had a pCR. MPR or pCR was 18/26 (69%) and in HPV- pts, 15/23 (65%). 2/11 pts had microscopic residual disease in 1 LN each. Conclusions: The combination of N and wkly PC was well tolerated. The primary endpoint of pCR at the primary site in > 11/37 pts was met with the 27th pt. Accrual continues. Exploratory outcomes assessing markers of immune bias in tumor tissue and plasma are in process. Clinical trial information: NCT03342911 .

Safety of perioperative atezolizumab in combination with FLOT versus FLOT alone in patients with resectable esophagogastric adenocarcinoma: An interim safety analysis of the DANTE, a randomized, open-label phase II trial of the German Gastric Group at the AIO and the SAKK.

2020 ◽  
Vol 38 (4_suppl) ◽  
pp. 398-398
Author(s):  
Salah-Eddin Al-Batran ◽  
Sylvie Lorenzen ◽  
Michael Schenk ◽  
Peter C. Thuss-Patience ◽  
Eray Goekkurt ◽  
...  
Keyword(s):  
Adverse Events ◽  
Disease Progression ◽  
Phase Ii ◽  
Phase Ii Trial ◽  
Clinical Stage ◽  
Locally Advanced ◽  
Safety Analysis ◽  
Open Label ◽  
Serious Adverse Events ◽  
Open Label Phase

398 Background: The DANTE study evaluates atezolizumab in the perioperative treatment of locally advanced, potentially resectable gastric or GEJ adenocarcinoma in combination with perioperative FLOT. Here, we report the protocol-defined interim safety analysis. Methods: DANTE is a large, multinational, prospective, multicenter, randomized, investigator-initiated, open label phase II trial. Patients (pts) with locally advanced, potentially resectable adenocarcinoma of the stomach and GEJ (≥cT2 and/or N-positive) without distant metastases are enrolled. Pts are randomized 1:1 to 4 pre-operative 2-week cycles (8 weeks) of FLOT followed by surgery and 4 additional cycles of FLOT plus atezolizumab at 840 mg every 2 weeks, followed by a total of 8 additional cycles of atezolizumab at 1200 mg every 3 weeks as monotherapy (arm A) or FLOT alone (arm B). Primary endpoint is time to disease progression or relapse after surgery (PFS/DFS). Results: Recruitment started in Sept 2018; by September 2019, a total of 122 pts have been randomized. This analysis is based on the first 40 pts (20 pts in each arm). The pts had a median age of 62 y and 75% of pts had an ECOG PS of 0 in both arms. The cohort was well balanced in terms of tumor location and clinical stage. 90% of pts enrolled completed all pre-operative cycles in each arm. Total number of adverse events with relation to study treatment was 154 in arm A and 148 in arm B. Total number of serious adverse events (SAE; related or not) was 16 in Arm A and 14 in arm B. 20% of pts in each arm had an SAE due to perioperative morbidity. No surgical mortality was observed. 18 and 19 pts proceeded to operation in arms A and B, respectively. Premature treatment discontinuation occurred in 2 pts in each arm: disease progression (1) and deterioration of general health condition (1) in arm A; and pts’ wish (1) and death (1) in arm B. Median hospitalization time was 15 days in arm A and 16 days in arm B. Conclusions: perioperative atezolizumab plus FLOT is feasible and safe. The study continued recruitment. Clinical trial information: NCT03421288.

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