Combination of weekly paclitaxel-carboplatin plus standard bevacizumab as neoadjuvant treatment in stage IB–IIB cervical cancer

2021 ◽  
pp. ijgc-2021-002432
Author(s):  
Charlotte Maene ◽  
Rawand Rokan Salihi ◽  
Els Van Nieuwenhuysen ◽  
Sileny N Han ◽  
Nicole Concin ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Response Rate ◽  
Residual Disease ◽  
Complete Response ◽  
Pathological Response ◽  
Weekly Paclitaxel ◽  
Adjuvant Chemoradiotherapy ◽  
Stromal Invasion ◽  
Stage Ib

ObjectiveIn this study we investigated response rates of bevacizumab in addition to weekly paclitaxel and carboplatin in neoadjuvant setting in cervical cancer stage IB–IIB.MethodsIn this retrospective study we included patients with FIGO 2018 stage IB–IIB cervical cancer. Treatment consisted of 9 weeks' neoadjuvant paclitaxel and carboplatin (paclitaxel 60 mg/m2, carboplatin AUC 2.7; both weekly) and bevacizumab (15 mg/kg every 3 weeks). The radiologic response rate was analyzed using the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 criteria. The definition of optimal pathological response was complete disappearance of tumor (complete response, pCR) or residual disease with less than 3 mm stromal invasion (pPR1). Suboptimal pathologic response (pPR2) was defined as persistent residual disease with more than 3 mm stromal invasion.ResultsA total of 30 patients were included. Six patients had FIGO 2018 stage IB1–IB2 (20%), one had stage IB3 (3%), five had stage IIA (17%), and 18 had stage IIB (60%). After completing the neoadjuvant chemotherapy, all patients showed a RECIST response (seven (23%) complete response; 23 (77%) partial response). Six patients (20%) were judged to be still inoperable. After radical hysterectomy, optimal pathological response was observed in 11 patients (38%) (pCR in nine patients (29%) and pPR1 in two patients (8%)). Six patients (20%) received postoperative adjuvant chemoradiotherapy. Hematological toxicity was similar to neoadjuvant weekly paclitaxel and carboplatin, as we reported earlier. Grade IV proteinuria or hypertension was not observed and no administration of bevacizumab was delayed or dose-reduced.ConclusionBevacizumab in addition to weekly paclitaxel and carboplatin showed a 100% radiological RECIST response and an optimal pathological response of 38%. Although bevacizumab has an established role in the treatment of recurrent cervical cancer in combination with paclitaxel and carboplatin, we did not observe a tendency toward superior effect on the pathological response rate of bevacizumab in the neoadjuvant chemotherapy setting.

Use of carboplatinum as neoadjuvant setting for patients affected by locally advanced cervical cancer.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e15553-e15553
Author(s):  
Carlo De Cicco Nardone ◽  
Francesco Plotti ◽  
Michela Angelucci ◽  
Roberto Montera ◽  
Patrizio Damiani ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Response Rate ◽  
Locally Advanced ◽  
Complete Response ◽  
World Health ◽  
Advanced Cervical Cancer ◽  
Locally Advanced Cervical Cancer ◽  
Grade 3 ◽  
Health Organization

e15553 Background: The aim of this study is to evaluate the efficacy and safety of the combination of carboplatin and paclitaxel as neoadjuvant chemotherapy (NACT) in patients affected by locally advanced cervical cancer. Methods: Between June 2007 to May 2009, all patients with diagnosis of IB2-IIB cervical cancer were considered eligible for this protocol. All enrolled patients received 3 cycles of carboplatin (AUC6) and paclitaxel at 175 mg/mq in neadjuvant setting. The chemotherapy induced toxicity and response to the treatment were evaluated according to World Health Organization criteria. Results: We have enrolled 23 patients with diagnosis of locally advanced cervical cancer. A total of 22 patients completed planned 3 cycles of neoadjuvant chemotherapy. After 3 cycles of chemotherapy 9 out of 23 patients (42%) showed a complete response, 7 patients (35%) partial response, 5 patients (16%) stable disease and 2 patients (11%) showed disease progression. The most common toxicity was haematologic (43%), extra haematologic toxicities were nausea/vomiting, neuropathy and alopecia, that occurred in 45%, 13% and 25% respectively. No renal and grade 3 and 4 haematologic toxicities were registered. Conclusions: Our results suggest that the use of carboplatin, in neadjuvant setting, is a well tolerated drug, produces manageable toxicity with a response rate similar to standard cisplatin. Then, it rappresents a valid alternative in patients affected by locally advanced cervical cancer.

scholarly journals Efficacy of dose-intensive platinum-containing neoadjuvant chemotherapy in the combination treatment for locally advanced cervical cancer

2019 ◽  
Vol 14 (4) ◽  
pp. 56-64
Author(s):  
O. A. Smirnova ◽  
N. E. Bondarev ◽  
E. A. Ulrikh ◽  
N. A. Mikaya ◽  
A. S. Petrova ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Pathological Complete Response ◽  
Objective Response ◽  
Locally Advanced ◽  
Complete Response ◽  
Small Sample ◽  
Pathological Response ◽  
Advanced Cervical Cancer ◽  
Locally Advanced Cervical Cancer

Objective:to assess the efficacy of dose-intensive platinum-containing neoadjuvant chemotherapy in patients with FIGO stage IB2–IIB locally advanced cervical cancer.Materials and methods.We evaluated the efficacy and toxicity of 3 cycles of intravenous dose-intensive neoadjuvant chemotherapy with either AP regimen (cisplatin 75 mg/m2 and doxorubicin 35 mg/m2) or TP regimen (cisplatin 60 mg/m2 and paclitaxel 60 mg/m2).Results.The study included 105 patients (75 in the AP group and 30 in the TP group) aged between 27 and 63 years (mean age 44 years) with primary verified cervical cancer (T1–2B0–2Nx–0M0). Surgery was performed in 66 patients (88 %) from the AP group and 24 patients (80 %) from the TP group. Six patients (8 %) receiving AP regimen and 1 patient (3.3 %) receiving TP regimen developed disease progression. Four women (2.8 %) from the AP group developed relapses, whereas none of the patients from the TP group had relapses. Dose-intensive chemotherapy did not cause any significant complications at both chemotherapeutic and surgical stages. Our findings suggest that dose-intensive neoadjuvant chemotherapy is an effective method with an objective response rate of 84 % (63 cases) and 56.7 % (17 cases) in groups AP and TP respectively. Fifty-nine patients (78.7 %) receiving AP regimen had pathological response; of them, 7 participants (9.4 %) demonstrated pathological complete response (ypCR). In the TP group, 19 patients (63.3 %) had pathological response and 4 patients (13.4 %) had pathological complete response. Median follow-up time was 16.7 months (range: 3–29 months) in the AP group and 9.1 months (range: 2.8–12.7 months) in the TP group.Conclusion.Dose-intensive neoadjuvant chemotherapy can be considered as an alternative to standard treatment of locally advanced cervical cancer; however, further studies are needed due to the small sample size in this study.

scholarly journals Depth of Stromal Invasion as the Most Prognostically Relevant Regression System in Locally Advanced Cervical Cancer after Neoadjuvant Treatment: A Systematic Review and Meta-Analysis Grading

Diagnostics ◽  
2021 ◽  
Vol 11 (10) ◽  
pp. 1772
Author(s):  
Gian Franco Zannoni ◽  
Antonio Travaglino ◽  
Antonio Raffone ◽  
Damiano Arciuolo ◽  
Nicoletta D’Alessandris ◽  
...  
Keyword(s):  
Systematic Review ◽  
Cervical Cancer ◽  
Neoadjuvant Therapy ◽  
Prognostic Value ◽  
Meta Analysis ◽  
Residual Tumor ◽  
Complete Response ◽  
Pathological Response ◽  
Tumor Diameter ◽  
Stromal Invasion

Background: several different criteria have been proposed to categorize the pathological response in cervical cancer after neoadjuvant therapy; although it is unclear what the most prognostically valuable one is. Objective: to assess the prognostic value of pathological criteria for categorizing the response in cervical cancer after neoadjuvant therapy, through a systematic review and meta-analysis. Methods: four electronic databases were searched from January to December 2020 for all studies, assessing the prognostic value of pathological response in cervical cancer after neoadjuvant therapy. Hazard ratio (HR) for overall survival (OS) was calculated with a significant p-value < 0.05. A meta-analysis was performed for each criteria assessed in at least three studies. Results: sixteen studies were included. Criteria for pathological response included (i) residual stromal invasion < vs. >3 mm; (ii) complete response vs. any residual; (iii) proportion of viable cells; (iv) residual tumor diameter; and (v) intracervical vs. extracervical residual. Criteria (i) and (ii) were suitable for meta-analysis. The presence of a residual tumor with stromal invasion > 3 mm showed a HR of 4.604 (95% CI; 3.229–6.565; p < 0.001), while the presence of any residual showed a HR of 1.610 (95% CI; 1.245–2.081; p < 0.001); statistical heterogeneity was absent in both analyses. Conclusions: dichotomizing the pathological response in cervical cancer after neoadjuvant therapy as < vs. >3 mm stromal invasion is more prognostically valuable than dichotomizing as complete response vs. any residual. Further studies are necessary to evaluate other systems.

A phase II study of dose-dense neoadjuvant chemotherapy with weekly paclitaxel and carboplatin followed by chemoradiation in locally advanced cervical carcinoma.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 5104-5104
Author(s):  
Rajkumar Bikramjit Singh ◽  
Lalit Kumar ◽  
Subhash Chandra ◽  
B. K Mohanti ◽  
Sushmita Pathy ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Response Rate ◽  
Locally Advanced ◽  
Weekly Paclitaxel ◽  
Advanced Cervical Cancer ◽  
Locally Advanced Cervical Cancer ◽  
Grade 3 ◽  
Dose Dense

5104 Background: We prospectively studied dose dense neoadjuvant chemotherapy (NACT) designed for an enhanced cell kill, better local control and eradication of micrometastases prior to standard concurrent chemoradiation (CRT) in locally advanced cervical cancer. Methods: Between June 2010 and December 2011, 21 patients (median age - 51 years, range 35 - 67) of cervical cancer with locally advanced disease received NACT using paclitaxel (60mg/m2) and carboplatin (AUC-2) weekly for 6 doses. Patients (pts) then received concurrent CRT (external and brachytherapy) with weekly cisplatin (40mg/m2 for 6 doses) at a mean interval of 15 days (range 7–20 days). The primary end-point was response rate i.e. complete response (CR) and partial response (PR) 12 weeks post CRT. Results: Baseline stages were: stage 2A - 19%, 3B - 71.4%, 4A - 9.5%. Squamous cell carcinoma and adenocarcinoma constituted 95.2% and 4.7% pts respectively. Following NACT, 66.6% pts responded (CR -9.5% %; PR – 57.1 %), 23.8% had stable disease (SD) and 4.7% had progressive disease (PD). A total of 18 pts completed NACT and CRT of which 17 were in CR and 1 in PR. One patient with stage 4A disease developed vesicovaginal fistula at end of NACT for which she underwent pelvic exenteration and was in pathological CR. After NACT, one patient developed choroid metastases and was taken off study protocol while another patient was lost to follow up. At a mean follow up 5.8 months (range 1 - 14), 90% pts were in CR, 5% in PR and 5% had PD. During NACT, Grade 3/4 neutropenia, thrombocytopenia and anemia were seen in 33.3%, 4.7% & 9.5% of pts, respectively and grade 3/4 non-hematological toxicities in 9.5% pts. Following CRT, Grade 3/4 neutropenia, thrombocytopenia and anemia were seen in 25%, 5% and 10% of pts, respectively while 20% pts had grade 3/4 non-hematological toxicities. G-CSF was used in 30% pts during NACT and 25% pts during CRT, respectively. Conclusions: NACT with weekly paclitaxel and carboplatin followed by radical CRT is feasible and is associated with a high response rate in locally advanced cervical cancer. This approach needs to be studied in a phase III trial.

scholarly journals Prediction of pathological response following neoadjuvant chemotherapy in patients with muscle-invasive bladder cancer: the PRE-PREVENCYS trial

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
F. J. Hinsenveld ◽  
B. J. Noordman ◽  
J. L. Boormans ◽  
J. Voortman ◽  
G. J. L. H. van Leenders ◽  
...  
Keyword(s):  
Overall Survival ◽  
Bladder Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Residual Disease ◽  
Controlled Trial ◽  
Complete Response ◽  
Pathological Response ◽  
Invasive Bladder Cancer ◽  
Muscle Invasive Bladder Cancer ◽  
Muscle Invasive

Abstract Background The recommended treatment for patients with non-metastatic muscle-invasive bladder cancer (MIBC) is neoadjuvant chemotherapy (NAC) and radical cystectomy (RC). Following NAC, 20–40% of patients experience a complete pathological response (pCR) in the RC specimen and these patients have excellent long-term overall survival. Subject to debate is, however, whether patients with a pCR to NAC benefit from RC, which is a major surgical procedure with substantial morbidity, and if these patients might be candidates for close surveillance instead. However, currently it is not possible to accurately identify patients with a pCR to NAC in whom RC might be withheld. The objective of this study is to assess whether pathological response in the RC specimen after NAC can be predicted based on clinical, radiological, and histological variables and on a wide set of molecular biomarkers assessed in tissue, blood and urine. Methods This is a multicentre, prospective cohort study, including patients with cT2a-T4a N0-N1 M0 urothelial cell MIBC who are scheduled to undergo cisplatin-based NAC followed by RC. Prior to start of therapy, a 2-Deoxy-2-[18F] fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) is performed. Response to NAC is evaluated by CT-scan. Blood and urine, including cytology, are prospectively collected for biomarker analyses before and after NAC. Immediately before RC, participants undergo cystoscopy with bimanual examination and a re-staging transurethral resection (TUR) of all visible cancerous lesions or with biopsies from scar tissue. Subsequently, RC is performed in all patients. Tissue from the diagnostic TUR, the re-staging TUR, and the RC specimen is examined for the presence of urothelial cancer carcinoma and DNA and RNA is isolated for molecular analysis. The primary endpoint is the pathological stage (ypTN) in the RC and ePLND specimen and its association with clinical response. Discussion If the PRE-PREVENCYS trial shows that the absence of residual disease after NAC in patients with MIBC is accurately predicted, a randomized controlled trial is scheduled comparing the overall survival of NAC plus RC versus NAC followed by close surveillance for patients with a clinically complete response (PREVENCYS trial). Trial registration Netherlands Trial Register: NL8678; Registered 20 May 2020 https://www.trialregister.nl/trial/8678

Weekly nab-paclitaxel in combination with cisplatin as neoadjuvant chemotherapy in patients (pts) with locally advanced esophageal squamous cell carcinoma (SCC): Preliminary results of a phase study.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e15062-e15062
Author(s):  
Youhua Jiang ◽  
Fan Yun ◽  
Qixun Chen ◽  
Xinming Zhou ◽  
Zhiyu Huang ◽  
...  
Keyword(s):  
Adjuvant Chemotherapy ◽  
Neoadjuvant Chemotherapy ◽  
Response Rate ◽  
Locally Advanced ◽  
Disease Free Survival ◽  
Pathological Response ◽  
Adjuvant Chemoradiotherapy ◽  
R0 Resection ◽  
Resection Rate ◽  
Free Survival

e15062 Background: This phase II study was aimed to define the pathological response rate and safety of combining weekly nab-paclitaxel and cisplatin as neoadjuvant chemotherapy in pts with locally advanced esophageal SCC. Methods: Pts with resectable locally advanced thoracic esophageal SCC staged by EUS, CT and/or PET-CTscan. All pts received nab-paclitaxel (100 mg/m2, d1, d8, d22 and d29) and cisplatin (75 mg/m2, d1 and d22) as neoadjuvant chemotherapy, followed by esophagectomy.Postoperation: 2 cycles of adjuvant chemotherapy with same regimen was given in 4-6 weeks after the resection.The primary endpoint was pathological response rate. The second endpoints included R0 resection rate,down-staging rate, 3 years overall survival (OS) and progression-free survival (PFS). Results: From 01/2011 to 10/2012, 31 pts were enrolled . 28 male:3 females; II A/II B/III A/III B/III C in 2 (6.5%), 4 (12.9%), 9 ,(29.0%), 8 (25.8), and 8 (25.8%) pts. 26/31 pts went to surgery (83.9%). 26 had R0 resection (100%).Pathological complete response (pCR) was achieved in 3 pts (11.5%). Near pCR (microfoci of tumor cells on the primary tumor without lymph nodal metastases) in 1 pt (3.8 %). Down-staging was observed in 15 of 26 patiens (57.7%). 5 pts did not going to surgery: 2 for progressive disease (6.5%), 3 for refused. 20/26 pts (76.9%) received adjuvant chemotherapy,3 pts (11.5%) received adjuvant chemoradiotherapy. Grade 3/4 toxicities in 31 evaluable pts during chemotherapy were as follow: neutropenia (12.9%), anemia (6.5%), thrombocytopenia (3.2%), nausea/vomiting (12.9%), neutropenia fever (6.5%), asthenia (12.9%). Surgical complications: 1anastomotic leaks (3.8%). No treatment-related death. At a median follow up of 9 months, 26 pts were all disease-free survival. Conclusions: In pts with locally advanced esophageal SCC, weekly nab-paclitaxel and cisplatin as neoadjuvant chemotherapy achieved a high pathological response rate and R0 resection rate .The toxicity was well tolerated. Evaluation of nab-paclitaxel and cisplatin in randomized trials was warranted. Clinical trial information: NCT01258192.

scholarly journals Pathological Response Rate of Paclitaxel Based Dose Dense and Conventional Neoadjuvant Chemotherapy in Locally Advanced Female Breast Cancer Patients

2021 ◽  
Vol 10 (40) ◽  
pp. 3515-3519
Author(s):  
Nonam Chellappan ◽  
Smitha G. Raj
Keyword(s):  
Breast Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Cancer Patients ◽  
Response Rate ◽  
Locally Advanced ◽  
Female Breast Cancer ◽  
Pathological Response ◽  
Weekly Paclitaxel ◽  
Breast Cancer Patients ◽  
Female Breast

BACKGROUND Locally advanced female breast cancer patients have the highest risk of recurrence and distant metastasis. Taxane-based neoadjuvant chemotherapy gives a more pathological response. The purpose of this study was to assess the pathological response rate of paclitaxel-based dose-dense and conventional neoadjuvant chemotherapy in locally advanced female breast cancer patients. METHODS In this observational study, a total of hundred locally advanced female breast cancer patients were randomly selected for neoadjuvant chemotherapy. Fifty patients received three weekly paclitaxel 200 mg/m2 (4 courses) and other fifty patients received weekly paclitaxel 80 mg/m2 (10 courses) along with three weekly doxorubicin 50 mg/m2(4 courses in both arms). Chemotherapy-induced clinical response in both arms was weekly assessed by tumour and lymph node size measurements, change in consistency and fixity. Pathological response of chemotherapy in each arm was assessed by taking the difference of mean tumour volumes and presence of chemotherapy-induced fibrosis and collections of histiocytes in lymph nodes. RESULTS There was statistically significant pathological reduction after neoadjuvant chemotherapy was seen in three weekly arms (68.18 cm3 to 37.22 cm3 P-value 0.000), in the weekly arm (68.42 cm3 to 18.04 cm3 P-value 0.000) and difference in reduction of tumour volume (more in weekly arm -50.38 cm3 versus 30.86 cm3, Pvalue 0.000). CONCLUSIONS Locally advanced female breast cancer patients receiving neoadjuvant chemotherapy with paclitaxel showed a better pathological response rate. It was more in the weekly paclitaxel arm. KEY WORDS Pathological Response Rate, Neoadjuvant Chemotherapy, Locally Advanced.

A Modified Shortened Administration Schedule for Neoadjuvant Chemotherapy With Irinotecan and Cisplatin in Locally Advanced Cervical Cancer

2011 ◽  
Vol 21 (4) ◽  
pp. 685-689 ◽  
Author(s):  
Yufeng Ren ◽  
Yanfang Li ◽  
Jihong Liu
Keyword(s):  
Cervical Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Response Rate ◽  
Locally Advanced ◽  
Complete Response ◽  
Advanced Cervical Cancer ◽  
Administration Schedule ◽  
Locally Advanced Cervical Cancer ◽  
Grade 3 ◽  
Clinical Records

Introduction:The commonly used administration schedule of irinotecan in combination therapy with cisplatin in cervical cancer was once weekly for 3 weeks. To some extent, this administration schedule may be inconvenient for patients who were far from hospital. The aim of the current study is to investigate the efficacy and toxicities of a modified shortened administration schedule for neoadjuvant chemotherapy with irinotecan and cisplatin in locally advanced cervical cancer.Methods:We retrospectively reviewed the clinical records of patients with cervical cancer who received neoadjuvant chemotherapy with irinotecan and cisplatin delivered by the modified administration schedule at Sun Yat-sen University Cancer Center from November 2005 to May 2010. Irinotecan was administrated by intravenous infusion for 1 hour at a dose of 80 mg/m2on days 1 and 8. Cisplatin was administrated intravenously at a total dose of 60 to 70 mg/m2, which was infused on day 1 or was divided into 2 or 3 doses and given on days 1 to 2 or 3. The treatment was repeated every 3 weeks.Results:The total response rate was 78.8% (42/52), including a complete response and partial response rate of 11.5% (6/52) and 67.3% (35/52), respectively. Pathologically confirmed complete response was noted in 7.7% (4/52) of patients. Stable disease was observed in 17.3% (9/52) of patients and progression disease in 3.8% (2/52) of patients. Diarrhea and hematological toxicity were the major dose-limiting toxicities. Diarrhea occurred in 23.1% of patients with grades 1, 2, and 3 in 11.5%, 7.7%, and 3.8% of patients, respectively. No grade 4 diarrhea was noted. Grade 3/4 neutropenia developed in 7.7% (4/52) of patients. Grade 3/4 anemia occurred in 19.2% (10/52) of patients.Conclusions:The modified shortened administration schedule of combined therapy with irinotecan and cisplatin may be active against cervical cancer as neoadjuvant chemotherapy. The adverse effects could be controllable.

VEGF and Cervical Cancer Stage IB – IIA Response after Chemotherapy with Ifosfamide – Cisplatin

2019 ◽  
Vol 2 (3) ◽  
pp. 117-122
Author(s):  
Deri Edianto
Keyword(s):  
Cervical Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Tumor Size ◽  
Complete Response ◽  
Cancer Stage ◽  
Vegf Expression ◽  
Stage Ib ◽  
Cervical Biopsy ◽  
Biopsy Tissue ◽  
Chemotherapy Adjuvant

The aim of this study is to evaluate response of cervical cancer stage IB – IIA after neoadjuvant chemotherapy based on VEGF expression. The data were collected from 51 patients’ cervical cancer stage IB – IIA parafin blocks who received chemotherapy ifosfamide – cisplatin before radical hysterectomy at General Hospital Adam Malik Medan. VEGF expression was evaluated from cervical biopsy tissue, and response therapy was evaluated based on tumor size clinically. 20 out of 51 samples with clinically complete response, and the rest are partial response. 18 out of 20 samples with clinically complete response have negative or weak VEGF expression, and 31 out of 51 samples patients were partialy response with moderate or strong VEGF expression. 23 cases with tumor size > 4 cm and 23 cases stage IIA expressed VEGF moderately or strong. Cervical cancer with tumor size < 4 cm and cervical cenncer stage IB with less expressed of VEGF have good response with chemotherapy adjuvant ifosfamide – cis platin.Keyword: ifosfamide-cisplatin, cervical cancer, VEGF

scholarly journals PD-L1 Expression after Neoadjuvant Chemotherapy in Triple-Negative Breast Cancers Is Associated with Aggressive Residual Disease, Suggesting a Potential for Immunotherapy

Cancers ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 746
Author(s):  
Beatriz Grandal ◽  
Manon Mangiardi-Veltin ◽  
Enora Laas ◽  
Marick Laé ◽  
Didier Meseure ◽  
...  
Keyword(s):  
Neoadjuvant Chemotherapy ◽  
Triple Negative ◽  
Residual Disease ◽  
Checkpoint Inhibitors ◽  
Rapid Development ◽  
Complete Response ◽  
Tumor Burden ◽  
Small Subset ◽  
Breast Cancers ◽  
Residual Cancer Burden

The consequences of neoadjuvant chemotherapy (NAC) for PD-L1 activity in triple-negative breast cancers (TNBC) are not well-understood. This is an important issue as PD-LI might act as a biomarker for immune checkpoint inhibitors’ (ICI) efficacy, at a time where ICI are undergoing rapid development and could be beneficial in patients who do not achieve a pathological complete response. We used immunohistochemistry to assess PD-L1 expression in surgical specimens (E1L3N clone, cutoff for positivity: ≥1%) on both tumor (PD-L1-TC) and immune cells (PD-L1-IC) from a cohort of T1-T3NxM0 TNBCs treated with NAC. PD-L1-TC was detected in 17 cases (19.1%) and PD-L1-IC in 14 cases (15.7%). None of the baseline characteristics of the tumor or the patient were associated with PD-L1 positivity, except for pre-NAC stromal TIL levels, which were higher in post-NAC PD-L1-TC-positive than in negative tumors. PD-L1-TC were significantly associated with a higher residual cancer burden (p = 0.035) and aggressive post-NAC tumor characteristics, whereas PD-L1-IC were not. PD-L1 expression was not associated with relapse-free survival (RFS) (PD-L1-TC, p = 0.25, and PD-L1-IC, p = 0.95) or overall survival (OS) (PD-L1-TC, p = 0.48, and PD-L1-IC, p = 0.58), but high Ki67 levels after NAC were strongly associated with a poor prognosis (RFS, p = 0.0014, and OS, p = 0.001). A small subset of TNBC patients displaying PD-L1 expression in the context of an extensive post-NAC tumor burden could benefit from ICI treatment after standard NAC.

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