Pathologic complete response (pCR) with weekly nanoparticle albumin bound (nab-P) plus carboplatin (C) followed by doxorubicin plus cyclophosphamide (AC) with concurrent bevacizumab (B) for triple-negative breast cancer (TNBC).

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 1068-1068 ◽  
Author(s):  
Jessica Nicole Snider ◽  
Jasgit C. Sachdev ◽  
Jeffrey Warren Allen ◽  
Lee Steven Schwartzberg ◽  
Robyn R. Young ◽  
...  
Keyword(s):  
Pathologic Complete Response ◽  
Complete Response ◽  
Grade 5 ◽  
Safety Population ◽  
Individual Contributions ◽  
Serial Serum ◽  
The Individual ◽  
Tumor Biopsies ◽  
Clinical Trial Information ◽  
Efficacy Population

1068 Background: TNBC are mostly “basal-like” tumors, that have been shown to overexpress Secreted Protein Acidic and Rich in Cysteine (SPARC). Endothelial transcytosis of nab-P via albumin- gp60 -cav1 and binding of albumin to SPARC results in high intratumoral levels of nab-P. Exploiting this and the dysfunctional DNA repair in basal tumors, we hypothesized that nab-P + C would produce high rates of pCR in TNBC, further enhanced by antiangiogenesis properties of B. Methods: Eligible women had operable TNBC ≥ 2 cm. pCR in the breast and pCR in the breast + nodes were primary & secondary end points respectively. We needed 57 evaluable patients to demonstrate 40% pCR vs. 25% (P0) in a single stage phase II design (α: 0.05, β: 0.2).Schema: C AUC 6 d1 + nab-P 100mg/m2d 1, 8 & 15 Q 28 d x 4 cycles followed by AC d1, Q14d x 4 cycles preoperatively with B 10mg/kg Q 14d for the first 6 cycles of preoperative chemotherapy, resuming postoperatively to complete 1 year of treatment.Baseline tumor biopsies & serial serum/blood samples were collected. Results: Due to slow accrual, study was closed after 42 patients. They were women between 35 and 68 years of age (median 52); 51% were African American and 46% were node positive. Safety population: N=41. Four patients came off study prior to surgery while 7 are still on pre-op treatment. Grade ¾ hematologic AEs: neutropenia (Gr3: 56%; Gr4:24%) febrile neutropenia (4%), thrombocytopenia (32%), anemia (22%). 7 patients had SAEs, with 1 grade 5 event. To date, thirty of 31 patients who had surgery (efficacy population) are considered evaluable per protocol. In-breast pCR rates are 55% (17/31) and 56% (17/30) and the rates of pCR breast + nodes are 52% (16/31) and 53% (16/30), for the efficacy and evaluable populations respectively. Conclusions: Majority of the patients in our study achieved a pCR, which is among the highest rates reported compared to anthracyclines+ taxanes without B in TNBC. Correlative analyses are planned. An ongoing randomized intergroup study is evaluating the individual contributions of carboplatin & bevacizumab to pCR in TNBC. Clinical trial information: NCT00777673.

Durvalumab (D) and PET-directed chemoradiation (CRT) after induction FOLFOX for esophageal adenocarcinoma.

2021 ◽  
Vol 39 (3_suppl) ◽  
pp. 226-226
Author(s):  
Geoffrey Yuyat Ku ◽  
Abraham Jing-Ching Wu ◽  
Smita Sihag ◽  
Bernard J. Park ◽  
David Randolph Jones ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Pathologic Complete Response ◽  
Complete Response ◽  
Type I ◽  
Anastomotic Complication ◽  
Median Length ◽  
Siewert Type ◽  
Pet Ct ◽  
Positive Results ◽  
Clinical Trial Information

226 Background: Based on the positive results of the CALGB 80803 study (J Clin Oncol 2017;35:1 [abstr]), we have added D to induction FOLFOX and pre-op CRT. Methods: Patients (Pts) had TanyN+ or T3-4NanyM0 esophageal and Siewert Type I-III GEJ adenocarcinoma staged by EUS, PET/CT and CT. Pts received mFOLFOX6 ×2 prior to repeat PET/CT. PET responders (PETr) received 5-FU or capecitabine and oxaliplatin with RT to 50.4Gy, while induction PET non-responders (PETnr) received carboplatin/paclitaxel with RT. All Pts received D 1,500 mg q4W ×2 starting 2 wks prior to and during CRT. Esophagectomy was planned 6-8 weeks after CRT. Pts who had R0 resections received adjuvant D 1,500mg q4W ×6. Results: 36 Pts have been enrolled: 25 GEJ, 11 esophageal; 23 N+ and 32 T3/4. 26 of 36 Pts (72%) are PETr. 2 Pts developed metastatic disease after CRT and 9 Pts remain on preop treatment. 25 Pts have had surgery (Table). Pathologic complete response (pCR) was seen in 6 (24%); 5 Pts (20%) had ypT1N0 tumors with 99% response and 2 Pts (8%) had ypT0N1 with 99% response. 20 Pts (80%) had >90% response. 3 Pts had MSI tumors (2 PETr; 1 pCR, 1 T1aN0 99% response, 1 ypT2N0 90% response). Notable grade (gd) 3/4 adverse events (AEs) observed were neutropenia in 8 Pts (22%), diarrhea and vomiting in 2 Pts each (6%). Notable gd 1/2 AEs in ≥20%: anemia (31 Pts), thrombocytopenia (29 Pts), nausea (21 Pts), fatigue (25 Pts), increased AST (20 Pts), constipation and diarrhea (9 Pts), diarrhea (8 Pts). Immune-related AEs noted were gd 2 dermatitis (2 Pts), gd 3 hepatitis and gd 1 hypothyroidism in 1 Pt each. Median length of post-op stay was 8 days, with 12% anastomotic complication rate, including 1 Pt who died of hematemesis 16 days after discharge from 55-day hospitalization. Conclusions: The addition of D to induction FOLFOX and PET-directed CRT is safe and feasible. pCR and near-pCR in ½ of operated Pts is encouraging and compares favorably to the pCR rate of 31% in CALGB 80803 Pts who received induction FOLFOX. The final pCR rate and correlatives for the fully accrued study will be presented. Clinical trial information: NCT02962063. [Table: see text]

scholarly journals Chemotherapy induces dynamic immune responses in breast cancers that impact treatment outcome

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Yeon Hee Park ◽  
Samir Lal ◽  
Jeong Eon Lee ◽  
Yoon-La Choi ◽  
Ji Wen ◽  
...  
Keyword(s):  
Treatment Outcome ◽  
Pathologic Complete Response ◽  
Tumor Infiltrating Lymphocytes ◽  
Transcriptome Profiling ◽  
Complete Response ◽  
Strongly Correlated ◽  
Breast Cancers ◽  
Breast Cancer Cohort ◽  
Tumor Biopsies ◽  
Infiltrating Lymphocytes

AbstractTo elucidate the effects of neoadjuvant chemotherapy (NAC), we conduct whole transcriptome profiling coupled with histopathology analyses of a longitudinal breast cancer cohort of 146 patients including 110 pairs of serial tumor biopsies collected before treatment, after the first cycle of treatment and at the time of surgery. Here, we show that cytotoxic chemotherapies induce dynamic changes in the tumor immune microenvironment that vary by subtype and pathologic response. Just one cycle of treatment induces an immune stimulatory microenvironment harboring more tumor infiltrating lymphocytes (TILs) and up-regulation of inflammatory signatures predictive of response to anti-PD1 therapies while residual tumors are immune suppressed at end-of-treatment compared to the baseline. Increases in TILs and CD8+ T cell proportions in response to NAC are independently associated with pathologic complete response. Further, on-treatment immune response is more predictive of treatment outcome than immune features in paired baseline samples although these are strongly correlated.

Results of randomized phase II trial of neoadjuvant carboplatin plus docetaxel or carboplatin plus paclitaxel followed by AC in stage I-III triple-negative breast cancer (NCT02413320).

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 516-516
Author(s):  
Priyanka Sharma ◽  
Bruce F. Kimler ◽  
Anne O'Dea ◽  
Lauren Elizabeth Nye ◽  
Yen Y. Wang ◽  
...  
Keyword(s):  
Pathologic Complete Response ◽  
Complete Response ◽  
Drug Regimen ◽  
Stage I ◽  
Treatment Delivery ◽  
Residual Cancer Burden ◽  
Randomized Phase Ii ◽  
Grade 3 ◽  
Clinical Trial Information ◽  
Carboplatin Auc

516 Background: Addition of neoadjuvant carboplatin (Cb) to paclitaxel (T) followed by doxorubicin + cyclophosphamide (AC) improves pathologic complete response (pCR) rate compared to T/AC in TNBC. An anthracycline-free regimen of Cb plus docetaxel (D) also yields high pCR rates in TNBC, and patients achieving pCR with this regimen demonstrate excellent 3-year outcomes without adjuvant anthracycline. This study was designed to compare the efficacy of neoadjuvant regimens CbT→AC and CbD in TNBC. Methods: In this multicenter study, eligible patients with stage I–III TNBC were randomized (1:1) to either paclitaxel 80 mg/m2 every week X 12 + carboplatin (AUC 6) every 3 weeks X 4, followed by doxorubicin 60 mg/m2 + cyclophosphamide 600 mg/m2 every 2 weeks X 4 (CbT→AC, Arm A), or to carboplatin (AUC 6) + docetaxel (75 mg/m2) every 21 days X 6 cycles (CbD, Arm B). The primary endpoint was pCR (no evidence of invasive tumor in the breast and axilla). The two regimens were compared for differences in pCR, residual cancer burden (RCB), treatment delivery, and toxicity. Results: Between 2015 and 2018, 100 patients were randomized; 48 to Arm A and 52 to Arm B. Median age was 52 years, median tumor size was 2.7 cm, 30% were lymph node-positive and 17% carried a BRCA1/2 mutation. Baseline demographic and tumor characteristics were balanced between two arms. pCR was 55% (95%CI: 41%-59%) in Arm A and 52% (95%CI: 39%-65%) in Arm B, p =0.84. RCB 0+1 rate was 67% in both arms. Grade 3/4 adverse events were more common in Arm A compared to Arm B (73% vs 21%, p < 0.0001), with most notable differences in rates of G3/4 neutropenia (Arm A = 60%, Arm B = 8%, p = 0.0001), febrile neutropenia (Arm A = 18%, Arm B = 0%, p = 0.0001), and G3/4 anemia (Arm A = 46%, Arm B = 4%, p = 0.0001). 81% of Arm A patients completed all 4 doses of AC and 4 doses of Cb, and 71% completed > 9 doses of T. 90% of Arm B patients completed all 6 doses of CbD (p = 0.034). Conclusions: The non-anthracycline platinum regimen of CbD yields pCR and RCB 0+1 rates similar to 4-drug regimen of CbTàAC, but with a more favorable toxicity profile and higher treatment completion rate. The CbD regimen should be further explored as a way to de-escalate therapy in TNBC. Clinical trial information: NCT02413320.

Immunophenotype and proliferation to predict for response to neoadjuvant chemotherapy in TNBC: Results from BrighTNess phase III study.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 510-510 ◽  
Author(s):  
Otto Metzger Filho ◽  
Daniel G. Stover ◽  
Sarah Asad ◽  
Peter J Ansell ◽  
Mark Watson ◽  
...  
Keyword(s):  
Neoadjuvant Chemotherapy ◽  
Computational Analysis ◽  
Pathologic Complete Response ◽  
Complete Response ◽  
Phase Iii ◽  
Rna Seq ◽  
Immune Signature ◽  
T Cell Infiltration ◽  
Phase Iii Study ◽  
Clinical Trial Information

510 Background: In TNBC, the interplay between immunophenotype, tumor proliferation (prolif) and achievement of pathologic complete response (pCR) with neoadjuvant chemotherapy (NAC) remains unknown. Methods: RNA seq was performed on pre-tx research biopsies of stage II/III TNBC enrolled in BrighTNess. NAC regimens included paclitaxel alone or with carboplatin (Cb) or Cb plus veliparib, followed by AC. Computational analysis included subtyping (i.e. PAM50, Pietenpol), prolif (PAM50) and GeparSixto immune signature (GSIS). Cb-containing arms were combined due to similar pCR. Results: High quality RNA seq data was obtained from 482 of 634 pts. PAM50 classified 80.1% of tumors as basal-like. TNBC subtypes were mostly BL1 or BL2 (23.3%), IM (22.4%) or M/MSL (31.7%); 6% were LAR. pCR was higher for basal vs non-basal tumors (52.3% vs 35.4%, p = 0.003). IM had the highest pCR rate (64.2%, 95% CI 59.9%,68.5%). Basal-like was not a significant predictor for Cb benefit (p-interaction = 0.8). Prolif (OR = 0.30 p < 0.001) and GSIS (OR 0.68 p < 0.001) were significantly correlated with pCR but did not correlate with each other (Pearson’s r2 = 0.027). In multivariate analysis, prolif (HR = 0.36 95% CI, 0.21-0.61 p = 0.0002) and GSIS (HR = 0.62 95% CI, 0.49-0.79 p < 0.0001) increased the ability to predict pCR beyond standard clinico-pathologic variables (likelihood ratio = 14.9, p = 0.0001115). Among all pts, those above the median for both prolif. and GSIS had the highest pCR (67%; 84/125) while those below the median for both had the lowest pCR rate (34%; 42/125). Tumors with higher inferred CD8+ T-cell infiltration demonstrated greater benefit from Cb using either TIMER (HR = 0.83 [0.73-0.95]) or CIBERSORT (HR = 0.83 [0.76-0.91]). Tumors with higher inferred total macrophages, particularly immune suppressive M2 macrophages had a higher pCR rate on the non-Cb arm (AC-T) using CIBERSORT (HR = 1.27 [1.07,1.50]). Conclusions: Immunophenotype and proliferation are independent predictors of pCR to standard NAC regimens in TNBC. PAM50 is not a significant predictor of Cb benefit. Exploratory findings suggest that tumor infiltrating immunophenotype (i.e. CD8 T cells and macrophages) may predict response to specific NAC regimens in TNBC. Clinical trial information: NCT02032277.

Durvalumab (D) and PET-directed chemoradiation (CRT) after induction FOLFOX for esophageal adenocarcinoma.

2020 ◽  
Vol 38 (4_suppl) ◽  
pp. 394-394
Author(s):  
Michele Ly ◽  
Daniela Molena ◽  
Smita Sihag ◽  
Abraham Jing-Ching Wu ◽  
Pari M. Shah ◽  
...  
Keyword(s):  
Clin Oncol ◽  
Locally Advanced ◽  
Pathologic Complete Response ◽  
Safety Data ◽  
Complete Response ◽  
Type I ◽  
Siewert Type ◽  
Pet Ct ◽  
Clinical Trial Information ◽  
Locally Advanced Esophageal Cancer

394 Background: We previously presented safety data for the combination of D with carboplatin/paclitaxel (C/P) and RT for locally advanced esophageal cancer (J Clin Oncol 2018;36:172 [abstr]). Based on the positive results of the CALGB 80803 study (J Clin Oncol 2017;35:1 [abstr]), we amended the study to administer induction FOLFOX prior to PET assessment. Here, we present updated results. Methods: Patients (Pts) had TanyN+ or T3-4NanyM0 esophageal and Siewert Type I-III GEJ adenocarcinoma staged by EUS, PET/CT and CT. Pts received mFOLFOX6 ×2 prior to repeat PET/CT. PET responders (PETr) received 5-FU or capecitabine and oxaliplatin with RT to 50.4Gy, while PET non-responders (PETnr) received C/P with RT. All Pts received D 1,500 mg q4W ×2 starting 2 wks prior to and during CRT. Esophagectomy was planned 6-8 weeks after CRT. Pts who had R0 resections received adjuvant D 1,500mg q4W ×6. Results: 20 Pts have been enrolled: 16 GEJ, 4 esophageal; 3 T1-2N+, 8 T3-4N0, 1 T3Nx, 8 T3-4N+. 13 of 20 Pts (65%) are PETr. Of 13 Pts who have had surgery (8 PETr, all R0), pathologic complete response (pCR) was seen in 3 (23%; 2 PETr); 3 Pts (23%; all PETr) had ypT1bN0 tumors with 99% response and 1 Pt (8%; PETnr) had ypT0N1 (1/30 LN) with profound response in LN. 2 Pts had MSI tumors (1 PETr; 1 pCR, 1 ypT2N0 with 90% response). Notable gd 3/4 adverse events (AEs) observed were lymphopenia in 16 Pts (80%), neutropenia in 4 Pts (20%) and diarrhea and dysphagia in 1 Pt each (5%). Notable gd 1/2 AEs in ≥20%: thrombocytopenia (18 Pts), fatigue (13 Pts), anemia (12 Pts), increased AST (12 Pts), constipation (11 Pts), nausea (11 Pts), diarrhea (7 Pts) and odynophagia (7 Pts). Immune-related AEs noted were gd 3 hepatitis and gd 2 dermatitis in 1 Pt and gd 1 hypothyroidism in 1 Pt. Median length of post-op stay is 8 days, with 18% anastomotic complication rate. Conclusions: The addition of D to induction FOLFOX and PET-directed CRT is safe and feasible. pCR and near-pCR in ½ of Pts is encouraging and compares favorably to our historical pCR rate of 15% in PETr (Cancer 2016:122:2083) and pCR rate of 31% in CALGB 80803 Pts who received induction FOLFOX. Accrual to 36 Pts continues and updated outcomes and immune correlative data will be presented. Clinical trial information: NCT02962063.

scholarly journals Neoadjuvant Chemotherapy for Breast Cancer: Past, Present, and Future

2020 ◽  
Vol 14 ◽  
pp. 117822342098037
Author(s):  
Mariko Asaoka ◽  
Shipra Gandhi ◽  
Takashi Ishikawa ◽  
Kazuaki Takabe
Keyword(s):  
Breast Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Residual Disease ◽  
Early Stage ◽  
Locally Advanced ◽  
Pathologic Complete Response ◽  
Complete Response ◽  
Definitive Surgery ◽  
Individual Drug Response ◽  
The Individual

Neoadjuvant chemotherapy (NAC) had been developed as a systematic approach before definitive surgery for the treatment of locally advanced or inoperable breast cancer such as inflammatory breast cancer in the past. In addition to its impact on surgery, the neoadjuvant setting has a benefit of providing the opportunity to monitor the individual drug response. Currently, the subject of NAC has expanded to include patients with early-stage, operable breast cancer because it is revealed that the achievement of a pathologic complete response (pCR) is associated with excellent long-term outcomes, especially in patients with aggressive phenotype breast cancer. In addition, this approach provides the unique opportunity to escalate adjuvant therapy in those with residual disease after NAC. Neoadjuvant chemotherapy in breast cancer is a rapidly evolving topic with tremendous interest in ongoing clinical trials. Here, we review the improvements and further challenges in the NAC setting in translational breast cancer research.

Camrelizumab in combination with preoperative chemotherapy for locally advanced esophageal squamous cell carcinoma: A single-arm, open-label, phase II study.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e16072-e16072
Author(s):  
Feng Wang ◽  
Yu Qi ◽  
Xiangrui Meng ◽  
Qingxia Fan
Keyword(s):  
Clinical Trial ◽  
Phase Ii ◽  
Preoperative Chemotherapy ◽  
Locally Advanced ◽  
Pathologic Complete Response ◽  
Complete Response ◽  
Pathologic Response ◽  
R0 Resection ◽  
Efficacy And Safety ◽  
Clinical Trial Information

e16072 Background: At present, ESCC has a dismal prognosis with huge unmet clinical needs. With the potential benefit of combining PD-1 inhibitor with nCT, we conducted a phase II trial to assess the efficacy and safety of Camrelizumab plus nCT for locally advanced ESCC. Methods: 43 patients (pts) with histologically confirmed stage II/III/IVa(cT2-4aN0-3M0) ESCC were enrolled from February 2020 to February 2021.The study was divided into two stages, stage 1: we administered 1 cycle of camrelizumab for induction therapy (200 mg q2 weeks); stage2: pts received 2 cycle of camrelizumab (200 mg every 3 weeks) plus docetaxel and nedaplatin, followed by surgery within 4̃6 weeks after neoadjuvant therapy completion. Primary endpoint was major pathologic response (MPR). Secondary endpoints included pathologic complete response (pCR), R0 resection rate, disease-free survival (DFS) and overall survival (OS). Results: At the cutoff date of Feb 5, 2021, 43 eligible pts were enrolled (63% males, median age 66), neoadjuvant treatment was completed in 33 pts and is ongoing in 3 pts. Thus far 27 out of 33 pts were resected, 6 pts are planned to undergo surgery, 3 pts were not suitable for operation after evaluation,1 pt had interval metastases preoperatively, 1 pt declined surgery, 1 pt was allergic to camrelizumab, 1 pt died due to unknown reasons. All patients underwent an R0 resection. Postoperative pathology showed that TNM stage decreased in 23 pts with 85.19% reduction rate. 17 pts (62.96%) reached major pathologic response, 8 pts (29.63%) reached pathologic complete response (no surgery related mortality). The most common AEs (all grade, grade≥3) were reduced hemoglobin (53%, 0%), hypoproteinemia (26%, 0%), neutrophil (21%, 12%), TSH reduction (21%, 0%), increased blood lactate dehydrogenase (16%, 0%), hyperthyroidism (16%, 0%), elevated alanine aminotransferase (9%, 0%), fatigue (7%, 0%), rash (5%, 2%). Date for median DFS and OS were not matured. Conclusions: Camrelizumab in combination with preoperative chemotherapy followed by surgery for locally advanced ESCC showed promising downstaging effect and MPR with good tolerance, and its efficacy and safety could be further studied in later trials. Clinical trial information: NCT03917966. Clinical trial information: NCT03917966.

Sign in / Sign up

Export Citation Format

Share Document