Tumor Growth Rate as a Prognostic Factor for Metastatic or Recurrent Adenoid Cystic Carcinoma of the Head and Neck Patients Treated with Carboplatin Plus Paclitaxel

Abstract Background: Large prospective studies of chemotherapy for metastatic or recurrent adenoid cystic carcinoma (ACC) of the head and neck are lacking due to the rarity of ACC. The aim of this study is to evaluate the efficacy of carboplatin plus paclitaxel toward ACC and perform an exploratory investigation of the prognostic factors to investigate the optimal strategy for metastatic or recurrent ACC.Methods: We retrospectively analyzed recurrent or metastatic ACC patients treated with carboplatin plus paclitaxel between April 2007 and September 2019 in our hospital. Objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS) and overall survival (OS) were evaluated, and an exploratory analysis of the prognostic factors including tumor growth rate (TGR) was conducted.Results: A total of 26 ACC patients were enrolled. ORR and DCR were 11.5% and 76.9%; the median PFS and OS were 8.1 and 22.3 months, respectively. From the results of the multivariate analysis, higher (≥ 6%/month) TGR was associated with worse PFS (hazard ratio [HR] 7.00, 95%CI 1.34–36.53, p = 0.02) and OS (HR 29.33, 95%CI 3.38–254.80, p < 0.01). The median PFS (10.6 vs. 6.6 months, log-rank p < 0.05) and OS (48.5 vs. 16.9 months, log-rank p < 0.01) were significantly shorter in patients with higher TGR.Conclusions: Carboplatin plus paclitaxel showed modest efficacy for recurrent or metastatic ACC patients. Watchful waiting may be optimal for ACC patients with lower TGR. Systemic chemotherapy should be considered when TGR increases during active surveillance.

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Tumor growth rate as a prognostic factor for metastatic or recurrent adenoid cystic carcinoma of the head and neck patients treated with carboplatin plus paclitaxel

European Archives of Oto-Rhino-Laryngology ◽

10.1007/s00405-020-06481-y ◽

2020 ◽

Author(s):

Naoki Fukuda ◽

Yu Fujiwara ◽

Xiaofei Wang ◽

Akihiro Ohmoto ◽

Tetsuya Urasaki ◽

...

Keyword(s):

Growth Rate ◽

Prognostic Factor ◽

Tumor Growth ◽

Adenoid Cystic Carcinoma ◽

Head And Neck ◽

Tumor Growth Rate ◽

Adenoid Cystic

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Efficacy of cyclophosphamide, doxorubicin, and cisplatin for adenoid cystic carcinoma, and their relationship with the pre-chemotherapy tumor growth rate

Chinese Clinical Oncology ◽

10.21037/cco.2020.03.07 ◽

2020 ◽

Vol 9 (2) ◽

pp. 15-15

Author(s):

Hyerim Ha ◽

Bhumsuk Keam ◽

Chan-Young Ock ◽

Dae Seog Heo

Keyword(s):

Growth Rate ◽

Tumor Growth ◽

Adenoid Cystic Carcinoma ◽

Tumor Growth Rate ◽

Adenoid Cystic

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Apatinib in patients with recurrent or metastatic adenoid cystic carcinoma of the head and neck: a single-arm, phase II prospective study

Therapeutic Advances in Medical Oncology ◽

10.1177/17588359211013626 ◽

2021 ◽

Vol 13 ◽

pp. 175883592110136

Author(s):

Guopei Zhu ◽

Lin Zhang ◽

Shengjin Dou ◽

Rongrong Li ◽

Jiang Li ◽

...

Keyword(s):

Prospective Study ◽

Adenoid Cystic Carcinoma ◽

Head And Neck ◽

Phase Ii ◽

Response Rate ◽

Treatment Options ◽

Objective Response ◽

Progression Free Survival ◽

Adenoid Cystic ◽

Fatal Hemorrhage

Background: Apatinib, a vascular endothelial growth factor receptor (VEGFR) blocker, has demonstrated encouraging antitumor activities and tolerable toxicities in various cancer types. Recurrent or metastatic adenoid cystic carcinoma of the head and neck (R/MACCHN) carries a poor prognosis, and treatment options are currently limited. This study was conducted to explore the antitumor activity and safety of apatinib in patients with R/MACCHN. Methods: In this phase II single-arm, prospective study, patients aged 15–75 years with incurable R/MACCHN received apatinib at a 500 mg dose once daily until intolerance or progression occurred. The primary endpoint was the 6-month progression-free survival (PFS) rate based on RECIST version 1.1. The secondary endpoints included response rate, overall survival (OS), and safety. Efficacy was assessed in all dosed patients with at least one post-baseline tumor assessment. Results: Among 68 patients treated with apatinib, 65 were evaluable for efficacy analysis, with a median follow-up time of 25.8 months. The 6-month, 12-month, and 24-month PFS rates were 92.3% [95% confidence interval (CI): 83–97.5%], 75.2% (95% CI: 61.5–84.0%) and 44.7% (95% CI: 32.3–57.5%), respectively. The objective response rate (ORR) and disease control rate (DCR), as assessed by investigators, were 46.2% (95% CI: 33.7–59.0%) and 98.5% (95% CI: 91.7–100.0%), respectively. The median duration of response was 17.7 months [interquartile range (IQR) 14.0–20.9]. The 12-month and 24-month OS rates were 92.3% (95% CI: 83.0–97.5%) and 82.3% (95% CI: 70–90.4%), respectively. The most common adverse events of grades 3–4 were hypertension (5.9%), proteinuria (9.2%), and hemorrhage (5.9%). One patient developed a fatal hemorrhage. Conclusion: An encouraging PFS, a high ORR, and a manageable safety profile were observed in this study. It seems that the administration of apatinib in R/MACCHN is likely to have a clinically meaningful therapeutic benefit and warrants further investigation. This study was prospectively registered in ClinicalTrials.gov (NCT02775370; date of registration: 17 May 2016; date of first patient enrollment: 25 May 2016)

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Tumor growth rate as an early indicator of the efficacy of anti-PD-1 immunotherapy in advanced melanoma.

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.15_suppl.e21050 ◽

2019 ◽

Vol 37 (15_suppl) ◽

pp. e21050-e21050 ◽

Cited By ~ 1

Author(s):

Bixia Tang ◽

Zhihong Chi ◽

Xinan Sheng ◽

Lu Si ◽

Chuanliang Cui ◽

...

Keyword(s):

Growth Rate ◽

Clinical Trials ◽

Tumor Growth ◽

Objective Response ◽

Antibody Therapy ◽

Progression Free Survival ◽

Tumor Growth Rate ◽

Imaging Data ◽

Pretreatment Period ◽

Tumor Measurements

e21050 Background: As immunotherapeutics take longer time to show clinical efficacy compared with chemotherapy and targeted therapy, it is critical to select patients with low tumor growth rate (TGR) prior immunotherapy as to get sufficient time for immunotherapeutics to play functions. However, which threshold of TGR before immunotherapy may be associated with good outcome remains unknown. Methods: Medical records from patients with advanced refractory melanoma prospectively treated in clinical trials (NCT02836795 and NCT03013101) of anti-PD-1 antibody toripalimab were analyzed. TGR was computed during the pretreatment period (reference) and the treatment period (treatment). Associations between TGR and objective response at the first evaluation, progression free survival (PFS), overall survival (OS) were computed. Results: We analyzed a total of 142 patients enrolled in these two clinical trials. Excluded for no measurable lesions in pretreatment period or incomplete imaging data through the pretreatment/treatment periods, a total of 90 patients could be explored for the relationship of TGR and the efficacy of anti-PD-1 antibody. TGR and hyperprogression were defined as Champiat S. used to make. The distribution of TGR is as follows: median 63.7 (range: -51~720). A total of 15 (16.7%), 41 (45.6%), 34 (37.8%) and 0 patients exhibited PR, SD, PD, CR, respectively. An association between lower TGR (TGR ≤55) and objective response was observed (P≤0.001). Among evaluable patients at week 8, 83.9% (13+34/56) and 26.5% (2+7/34) showed PR/SD from baseline tumor measurements for the group of TGR≤55 and TGR > 55, respectively. Median PFS was 5.5 0.9m in the group of TGR≤55 compared 1.8 0.4m in the group of TGR > 55 (P≤0.001). Median OS was not reached in the group of TGR≤55 group and was 15.9 1.8m in the group of TGR > 55 (p = 0·02). Two patients were confirmed pseudoprogression in the follow-up. The TGR of these two patients was lower than 55. Five patients experienced hyperprogression. The TGR of each patient was 9, 12, 54, 56, 78, respectively. Conclusions: Melanoma patients with TGR≤55 prior anti-PD-1 antibody therapy are more likely to benefit from this regimen. However, it could not predict patients who may develop hyperprogression after anti-PD-1 antibody therapy. Clinical trial information: NCT02836795 and NCT03013101.

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A randomized phase II study of pembrolizumab with or without radiation in patients with recurrent or metastatic adenoid cystic carcinoma.

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.15_suppl.6082 ◽

2019 ◽

Vol 37 (15_suppl) ◽

pp. 6082-6082 ◽

Cited By ~ 3

Author(s):

Jonathan Daniel Schoenfeld ◽

Umair Mahmood ◽

Yu-Hui Chen ◽

Raymond H. Mak ◽

Jochen H. Lorch ◽

...

Keyword(s):

Adenoid Cystic Carcinoma ◽

Phase Ii ◽

Randomized Study ◽

Objective Response ◽

Progression Free Survival ◽

Distant Recurrence ◽

High Rate ◽

Tumor Growth Rate ◽

Adenoid Cystic ◽

Immune Biomarkers

6082 Background: Adenoid cystic carcinoma (ACC) is a salivary gland malignancy characterized by a high rate of distant recurrence. Systemic therapy has generally failed to produce durable benefit. Radiation (RT) is used for localized disease and as directed treatment for metastases. Here, we report the safety and efficacy of pembrolizumab (pembro) administered with or without hypofractionated RT in a phase II randomized study. Methods: Eligible patients (pts) had recurrent or metastatic ACC with evidence of progressive disease (PD) within the last 12 mos and >=1 measurable non-CNS lesion, along with 1-5 additional lesions deemed appropriate for RT to 30 Gy in 5 fractions. Pts were randomized to pembro alone (200 mg IV q3 weeks) or in combination with RT given within 7 days of cycle 1, day 1. The primary endpoint was objective response rate (ORR) outside the RT field by RECIST 1.1. Using a parallel two-stage design, if >=1 response out of 10 was observed in either arm, 10 more pts would be enrolled to that arm. If >=3 responded, the null hypothesis (ORR=5%) would be rejected in favor of a 25% ORR. Predefined secondary endpoints included progression free survival (PFS) and toxicity. Analyses of tumor growth rate (TGR) excluding RT lesions and immune biomarkers were exploratory. Results: Ten pts per arm were randomized into the trial’s first stage with median age 65 (45-79). No objective responses were seen. Stable disease (SD) was observed in 13 pts; 6 had PD as best response, 1 was unevaluable. Median PFS was 7 mos 95% CI (3 - 13 mos), with 9 pts without progression at 6 mos. 3 pts remain on study treatment (range 8-11 mos). In pts with SD, TGR decreased by >25% in 7 of 12 pts and by >75% in 4 pts. There was no difference in likelihood of SD or PFS between arms. Treatment related AEs (TRAEs) occurred in 18 pts but there were no G3-5 TRAEs. Among 8 biopsies analyzed, PD-L1+ tumor/immune cells ranged from 12-52%. Conclusions: Pembro alone or with hypofractionated RT was well tolerated. We observed no objective responses, but 65% of pts with PD prior to study entry achieved SD, the majority with decreased TGR, and 15% had prolonged SD. Additional strategies are needed to further delay progression and effect response. Clinical trial information: NCT03087019.

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