scholarly journals A Prospective Phase II Study of Simultaneous Modulated Accelerated Radiotherapy Concurrently With CDDP/S1 for Esophageal Squamous Cell Carcinoma in the Elderly

2021 ◽  
Vol 11 ◽  
Author(s):  
SuPing Guo ◽  
FangJie Liu ◽  
Hui Liu ◽  
YingJia Wu ◽  
XuHui Zhang ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Esophageal Squamous Cell Carcinoma ◽  
Gross Tumor Volume ◽  
Tumor Volume ◽  
Tumor Response ◽  
Response Rate ◽  
Phase Ii Study ◽  
Accelerated Radiotherapy ◽  
Grade 3 ◽  
Ecog Ps

BackgroundTo explore the efficacy and toxicity of simultaneous modulated accelerated radiotherapy (SMART) concurrently with cisplatin (CDDP) and S1 (tegafur/gimeracil/oteracil) in elderly patients with esophageal squamous cell carcinoma (ESCC).MethodsThis single-arm, phase II study enrolled pathologically confirmed, stage II–IVa ESCC of 70–80 years old and Eastern Cooperative Oncology Group performance status (ECOG PS) 0–2. Patients received SMART (64 Gy to gross tumor volume and 48 Gy to clinical target volume in 30 fractions) with concurrent CDDP (day 1 of each week) and S1 (days 1–14, 22–35). The primary endpoint was objective response rate (ORR). The secondary endpoints included progression-free survival (PFS), overall survival (OS) and toxicities.ResultsThirty-seven eligible patients were analyzed with median follow-up of 25.7 months for all and 46.1 months for survivors. The ORR was 88.9%. Patients with baseline weight loss <5% (p=0.050) and nutritional risk index (NRI) ≥105.2 (p=0.023) had better tumor response. Median PFS was 13.8 months with 2-year PFS of 37.5%. Median OS was 27.7 months with 2-year OS of 57.5%. OS was significantly associated with ECOG PS (p=0.005), stage (p=0.014), gross tumor volume (p=0.004), baseline NRI (p=0.036), baseline C-reactive protein (CRP) level (p=0.003) and tumor response (p=0.000). CRP level (p=0.016) and tumor response (p=0.021) were independently prognostic of OS. ≥grade 3 anemia, neutropenia and thrombocytopenia occurred in 2.7%, 10.8% and 13.5% of patients; ≥grade 3 esophagitis and pneumonitis occurred in 18.9% and 2.7% of patient, respectively.ConclusionSMART concurrently with CDDP/S1 yielded satisfactory response rate, survival outcome and tolerable treatment-related toxicities in elderly patients with ESCC. Further studies are warranted to validate the results.

scholarly journals Concurrent chemoradiotherapy with S-1 compared with concurrent chemoradiotherapy with docetaxel and cisplatin for locally advanced esophageal squamous cell carcinoma

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Xi-Lei Zhou ◽  
Chang-Hua Yu ◽  
Wan-Wei Wang ◽  
Fu-Zhi Ji ◽  
Yao-Zu Xiong ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Adverse Events ◽  
Esophageal Squamous Cell Carcinoma ◽  
Elderly Patients ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Concurrent Chemoradiotherapy ◽  
Response Rate ◽  
Locally Advanced ◽  
Grade 3

Abstract Background This retrospective study was to assess and compare the toxicity and efficacy of concurrent chemoradiotherapy (CCRT) with S-1 or docetaxel and cisplatin in patients with locally advanced esophageal squamous cell carcinoma (ESCC). Methods Patients with locally advanced ESCC who received CCRT with S-1 (70 mg/m2 twice daily on days 1–14, every 3 weeks for 2 cycles, S-1 group) or docetaxel (25 mg/m2) and cisplatin (25 mg/m2) on day 1 weekly (DP group) between 2014 and 2016 were retrospectively analyzed. Radiotherapy was delivered in 1.8–2.0 Gy per fraction to a total dose of 50–60 Gy. Treatment-related toxicities (Common Terminology Criteria for Adverse Events version 4.0), response rate, and survival outcomes were compared between groups. Results A total of 175 patients were included in this study (72 in the S-1 group and 103 in the DP group). Baseline characteristics were well balanced between the two groups. The incidence of grade 3–4 adverse events were significantly lower in the S-1 group than that of the DP group (22.2% vs. 45.6%, p = 0.002). In the DP group, elderly patients (> 60 years) had a significantly higher rate of grade 3–4 adverse events than younger patients (58.1% vs. 31.3%, p = 0.01). The objective overall response rate (complete response + partial response) was 68.1% in the S-1 group, and 73.8% the DP group (p = 0.497). The 3-year overall survival was 34.7% in the S-1 group, and 38.8% in the DP group (p = 0.422). The 3-year progression free survival in the DP group was higher than that in the S-1 group but without significant difference (33.0% vs. 25.0%, p = 0.275). Conclusion CCRT with S-1 is not inferior to CCRT with docetaxel and cisplatin and is better tolerated in in elderly patients with locally advanced ESCC.

scholarly journals The Predictive Value of Tumor Volume, Inflammatory Biomarkers, and Their Dynamic Changes on Early Tumor Response for Elderly Patients With Esophageal Squamous Cell Carcinoma Underwent Radiotherapy

2021 ◽  
Author(s):  
Shuai Liang ◽  
Chengming Li ◽  
Lu Wang ◽  
Dongshui Xu ◽  
Zhao Liu ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Esophageal Squamous Cell Carcinoma ◽  
Elderly Patients ◽  
Cell Carcinoma ◽  
Tumor Volume ◽  
Tumor Response ◽  
Inflammatory Biomarkers ◽  
Dynamic Changes ◽  
Early Tumor Response ◽  
Early Tumor

Abstract Background: To investigate the tumor volume, pre-treatment inflammatory biomarkers (pre-IBs), and their dynamic changes on early tumor response (ETR) in elderly patients (≥70 years) with esophageal squamous cell carcinoma (ESCC) underwent radiotherapy.Methods: The ETR was assessed according to RECIST 1.1 at 1 month after radiotherapy. The tumor volume ((gross tumor volume (GTV) at the initial treatment planning (GTVi), and GTV at shrinking irradiation field planning (GTVs)), IBs (neutrophil/lymphocyte (NLR), platelet/lymphocyte (PLR), and lymphocyte/monocyte (LMR)) which also included during treatment IBs (dur-IBs), and clinical variables were collected and analyzed from 197 patients received radiotherapy at our institution between 2015 and 2020. The tumor volume change rate (TVCR) and dynamic changes of IBs (delta-IBs) were defined as follows: TVCR=(1-GTVs/GTVi)×100%, delta-IBs=1-dur-IBs/pre-IBs. A nomogram based on logistic regression analysis were then established for predicting ETR.Results: GTVi and pre-LMR significantly decreased, pre-NLR, and pre-PLR significantly increased during radiotherapy or chemoradiotherapy (all P<0.001). Multivariate analysis indicated that TVCR [OR, 0.197; 95%CI, 0.093-0.414; P<0.001], pre-NLR [OR, 2.568; 95%CI, 1.031-6.394; P=0.043], and delta-NLR [OR, 2.831; 95%CI, 1.126-7.119; P=0.027] were statistically significant with ETR. And c-index of the nomogram established by combining all independent predictors for ETR was 0.769 [95%CI, 0.161–0.302].Conclusion: TVCR, Pre-NLR, and delta-NLR were significant with ETR in elderly patients with ESCC who underwent radiotherapy. And the developed nomogram with superior prediction ability for ETR could assist in patients counseling and guide to make individual treatments and follow-up strategies.

Phase-II study of toripalimab combined with neoadjuvant chemotherapy for the treatment of resectable esophageal squamous cell carcinoma.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e16029-e16029
Author(s):  
Delin Liu ◽  
Qin Zhang ◽  
Jinghua Zhu ◽  
Ting Qian ◽  
Rong Yin ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Esophageal Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Neoadjuvant Therapy ◽  
Squamous Cell ◽  
Phase Ii Study ◽  
Locally Advanced ◽  
Neoadjuvant Treatment ◽  
Neoadjuvant Radiochemotherapy ◽  
Grade 3

e16029 Background: Compared with neoadjuvant chemotherapy alone，Neoadjuvant radiochemotherapy can significantly increase pCR rate in esophageal squamous cell carcinoma and improve patient overall survival. However, the addition of radiotherapy increases the risk of adverse reactions and surgery. Neoadjuvant radiochemotherapy is currently used in < 5% of Chinese patients.The purpose of this phase II study is to assess the efficacy and safety of toripalimab combined with paclitaxel and cisplatin as neoadjuvant treatment for resectable locally advanced esophageal squamous cell carcinoma(clinical trial registration number: ChiCTR1900025318). Methods: Patients 18–75 years old with esophageal squamous cell carcinoma confirmed by endoscopic biopsy, assessed to be locally advanced esophageal squamous cell carcinoma (cT1–cT2, N+; cT3–cT4 a, any N), and expected to be resectable were given toripalimab (240 mg d1 + PTX 175 mg/m2 + PDD 75 mg/m2 q3w) before surgery for two treatment cycles, followed by efficacy assessment. A consultation meeting with thoracic surgeons was held to assess radical surgery for patients with resectable lesions 4–6 weeks after neoadjuvant therapy was completed. pCR and postoperative-stage statistical analysis were conducted based on postoperative pathology test results. These results were used to determine the efficacy and safety of PD-1 monoclonal antibody combined with chemotherapy as neoadjuvant therapy for locally advanced esophageal cancer. Results: By December 2020, 23 subjects were enrolled. Of the subjects, five withdrew without undergoing surgery (three subjects refused surgery and switched to radical radiochemotherapy, one subject progressed to PD after two cycles of neoadjuvant therapy and switched to palliative treatment, and one subject could not undergo surgery after neoadjuvant treatment and gave up the treatment) and 18 evaluable patients underwent surgery. The R0 resection rate was 100%, and T0–Tis 33.3% (6/18) achieved pCR. Among these patients, 61.1% (11/18) achieved T0–T1 after surgery, and 72.2% (13/18) achieved N0. Moreover, stage reduction effects were significant compared with preoperative TN staging. Common side-effects include nausea, vomiting, neutropenia, thrombocytopenia, rash, asthenia, constipation, and muscle soreness. Most adverse events were grades 1–2, and grades 3/4 adverse events include one case of grade 3 neutropenia and one case of grade 3 diarrhea (suspected immune-related colitis), which improved after symptomatic treatment. Conclusions: Toripalimab combined with the TP scheme showed preliminary efficacy and controllable safety in the treatment of resectable locally advanced esophageal squamous cell carcinoma and is worthy of further exploration. Clinical trial information: ChiCTR1900025318.

scholarly journals Tumor Stage-Based Gross Tumor Volume of Resectable Esophageal Squamous Cell Carcinoma Measured on CT: Association With Early Recurrence After Esophagectomy

2021 ◽  
Vol 11 ◽  
Author(s):  
Yu-ping Wu ◽  
Sun Tang ◽  
Bang-guo Tan ◽  
Li-qin Yang ◽  
Fu-lin Lu ◽  
...  
Keyword(s):  
Risk Factors ◽  
Squamous Cell Carcinoma ◽  
Esophageal Squamous Cell Carcinoma ◽  
Predictive Models ◽  
Gross Tumor Volume ◽  
Roc Analysis ◽  
Tumor Volume ◽  
Tumor Stage ◽  
Early Recurrence ◽  
Independent Risk Factors

ObjectiveTo investigate relationship of tumor stage-based gross tumor volume (GTV) of esophageal squamous cell carcinoma (ESCC) measured on computed tomography (CT) with early recurrence (ER) after esophagectomy.Materials and MethodsTwo hundred and four consecutive patients with resectable ESCC including 159 patients enrolled in the training cohort (TC) and 45 patients in validation cohort (VC) underwent contrast-enhanced CT less than 2 weeks before esophagectomy. GTV was retrospectively measured by multiplying sums of all tumor areas by section thickness. For the TC, univariate and multivariate analyses were performed to determine factors associated with ER. Mann-Whitney U test was conducted to compare GTV in patients with and without ER. Receiver operating characteristic (ROC) analysis was performed to determine if tumor stage-based GTV could predict ER. For the VC, unweighted Cohen’s Kappa tests were used to evaluate the performances of the previous ROC predictive models.ResultsER occurred in 63 of 159 patients (39.6%) in the TC. According to the univariate analysis, histologic differentiation, cT stage, cN stage, and GTV were associated with ER after esophagectomy (all P-values &lt; 0.05). Multivariate analysis revealed that cT stage and GTV were independent risk factors with hazard ratios of 3.382 [95% confidence interval (CI): 1.533–7.459] and 1.222 (95% CI: 1.125–1.327), respectively (all P-values &lt; 0.05). Mann-Whitney U tests showed that GTV could help differentiate between ESCC with and without ER in stages cT1-4a, cT2, and cT3 (all P-values &lt; 0.001), and the ROC analysis demonstrated the corresponding cutoffs of 13.31, 17.22, and 17.83 cm3 with areas under the curve of more than 0.8, respectively. In the VC, the Kappa tests validated that the ROC predictive models had good performances for differentiating between ESCC with and without ER in stages cT1-4a, cT2, and cT3 with Cohen k of 0.696 (95% CI, 0.498–0.894), 0.733 (95% CI, 0.386–1.080), and 0.862 (95% CI, 0.603–1.121), respectively.ConclusionGTV and cT stage can be independent risk factors of ER in ESCC after esophagectomy, and tumor stage-based GTV measured on CT can help predict ER.

Phase II Study of Melphalan, Prednisone and Lenalidomide Combination for Newly Diagnosed Multiple Myeloma Patients Who Are Not Candidates for Stem Cell Transplantation

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 2769-2769
Author(s):  
Vivek Roy ◽  
A. Keith Stewart ◽  
P. Leif Bergsagel ◽  
Angela Dispenzieri ◽  
Kristina Laumann ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Phase I ◽  
Cell Transplantation ◽  
Phase Ii ◽  
Response Rate ◽  
Phase Ii Study ◽  
Grade 3 ◽  
Ecog Ps

Abstract Melphalan (M), Prednisone (P) and Lenalidomide (R) are active in the treatment of multiple myeloma (MM). We evaluated the toxicity and efficacy of MPR in a phase I/II trial. Results of phase I part were previously reported (Blood2006, 108(11) abst 3558). M 5 mg/m2 on days (d) 1–4, 60 mg/m2 d 1–4 and R 10 mg d 1–21 of a 28 day cycle was determined as MTD for the phase II study. Methods: Patients with previously untreated MM who were not candidates for stem cell transplantation, age ≥18 yr, ECOG PS 0–3, evaluable or measurable disease, ANC &gt;1500, platelets &gt; 100,000 and creatinine ≤ 3.0 mg/dL were eligible. All patients received aspirin 325 mg/d as DVT prophylaxis. Routine antibacterial prophylaxis was not used. G/GM-CSF was used at the discretion of the treating physician for neutropenia. Response rate (RR), confirmed on two consecutive determinations was the primary end-point. The study had 90% power to detect a RR of at least 45%. Results: Twenty-six patients were accrued between July ’06 and Feb ’08. The median age was 74 y (64 – 87y), 17 (65%) were men. Six, 13, 6, 1 (23%, 50%, 23%, and 4%) patients had ECOG PS 0, 1, 2, and 3, respectively. Three (12%), 11 (42%) and 10 (38%) patients were ISS stage 1, 2 and 3. A total of 106 cycles were administered; median 4.5 (1–13). Seventy-seven % patients experienced at least 1 grade 3 or 4 toxicity. Neutropenia (42%/8%) and thrombocytopenia (20%/8%) were the most common grade 3/4 adverse events followed by anemia (16%/0%), fatigue (8%/4%), rash (11%/0%), and hyperglycemia (4%/0%). There were 20 treatment delays in 9 patients, and 18 dose reductions (9 in R, 11 in M and 1 P) occurred in 7 patients, most commonly because of neutropenia or thrombocytopenia. Eleven patients (42%) required G-CSF treatment. Eleven patients are currently receiving treatment; 15 have gone off study (4 completed per protocol, 3 refused, 3 adverse effects, 3 unrelated illnesses, 2 other). Median follow up of survivors is 8 m (0 – 22m). Eighteen (69 %; 95%CI 48–86) patients had a PR or better according to International Myeloma Working Group Uniform Response criteria; 3 (12 %) CR, 5 (19 %) VGPR and 10 (38%) PR. Median number of cycles before achieving a response was 2 (1 – 11). Median Progression Free and Overall Survival is 16.7m (95% CI 11.2–23.0), and 23 m (95% CI: 22 – 23), respectively. Conclusions: MPR combination is feasible with a manageable toxicity profile and has significant activity in the treatment of patients with MM who are not candidates for stem cell transplant, with an overall response rate of 69%, and a CR plus VGPR rate of 31%. Grade 3 or 4 neutropenia and thrombocytopenia was the most common toxicity, seen in up to 50% of patients in this cohort of predominantly elderly patients. Dose reduction in R and/or M was required in 27% patients. No patient developed neuropathy or thromboembolic complications.

Volume reduction rate of the primary tumor as an objective clinical measure to evaluate efficacy of neoadjuvant chemotherapy for esophageal squamous cell carcinoma.

2018 ◽  
Vol 36 (4_suppl) ◽  
pp. 42-42
Author(s):  
Shinsuke Nagasawa ◽  
Takashi Ogata ◽  
Kentaro Hara ◽  
Hiroaki Osakabe ◽  
Masato Nakazono ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Neoadjuvant Chemotherapy ◽  
Esophageal Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Primary Tumor ◽  
Tumor Volume ◽  
Reduction Rate ◽  
Volume Reduction ◽  
Grade 3

42 Background: Neoadjuvant chemotherapy (NAC) followed by surgery is a standard treatment for esophageal squamous cell carcinoma (ESCC) in Japan. Efficacy of NAC on the primary tumor is clinically evaluated during NAC and before surgery and is pathologically examined after surgery. Clinical evaluation of the primary tumor is sometimes difficult because primary tumor is nonmesurable lesion and is usually evaluated subjectively, while pathological finding is objective and a gold standard to evaluate efficacy of NAC. In the present study, we tried to evaluate clinicaly efficacy objectively by calcurating tumor volume by esophagography and concordance between volume reduction rate and pathological efficacy. Methods: This retrospective study examined 53 patients who fullfilled the following criteria; (1) thoracic ESCC, (2) underwent resection following NAC between January 2011 and February 2017, and (3) T2-3N0 before surgey. Clinically, volume of the primary tumor was calculated by multiplying length and thickness in the lateral view of esophagography. Pathological efficacy was examined by the proportion of the tumor disappearance of the primary tumor and was classified as Grade 0-1 when degeneration area was < 2/3, Grade 2 when those area was > 2/3 and < 3/3, and Grade 3 when there was no residual tumor. Volume reduction rate calculrated by the difference of pre- and post-NAC was compared by stratifying pathological grade. Results: T2/T3 was 23/30, respectively. Regimen of neoadjuvant chemotherapy was 5-FU/CDDP in 50 patients,docetaxel/5-FU/CDDP in 1,and 5-FU/CDDP and Radiotherapy in 2. Overall volume reduction rate was 58.9% in median (range -127-100%). Pathological response (Grade 0-1/2/3) was 28/18/4, respectively. Median volume reduction rate (range) was 38.5% (-127-100%) in Grade 0-1, 72.2% (21.7-100%) in Grade 2, and 91.1% (75.5-100%) in Grade 3, which was significantly different (p < 0.01). Conclusions: The volume reduction rate of the primary tumor was correlated with pathological efficacy, suggesting that volume reduction rate could be a objective measure to evaluate efficacy of neoadjuvant chemotherapy for ESCC.

RATIONALE 302: Randomized, phase 3 study of tislelizumab versus chemotherapy as second-line treatment for advanced unresectable/metastatic esophageal squamous cell carcinoma.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 4012-4012
Author(s):  
Lin Shen ◽  
Ken Kato ◽  
Sung-Bae Kim ◽  
Jaffer A. Ajani ◽  
Kuaile Zhao ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Esophageal Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Disease Progression ◽  
Squamous Cell ◽  
Primary Endpoint ◽  
Systemic Therapy ◽  
Phase 3 ◽  
Grade 3 ◽  
Ecog Ps

4012 Background: Tislelizumab (tisle) monotherapy or plus chemotherapy demonstrated antitumor activity in patients (pts) with solid tumors, including esophageal squamous cell carcinoma (ESCC) (NCT03469557 and CTR20160872). Methods: In this global phase 3 study (NCT03430843), adults with histologically confirmed advanced/unresectable or metastatic ESCC whose disease progressed following prior systemic therapy with ≥1 evaluable lesion per RECIST v1.1 and an Eastern Cooperative Oncology Group performance score (ECOG PS) of ≤1 were included. Pts were randomized (1:1) to receive tisle 200 mg intravenously every 3 weeks or investigator-chosen standard chemotherapy ([ICC]; paclitaxel, docetaxel, or irinotecan) and treated until disease progression, unacceptable toxicity, or withdrawal. Stratification factors included ICC option, region, and ECOG PS. The primary endpoint was overall survival (OS) in the intent-to-treat (ITT) population. The key secondary endpoint was OS in the programmed death-ligand 1 (PD-L1)+ population (visually-estimated combined positive score [vCPS] ≥10%, by VENTANA PD-L1 SP263 assay). Other secondary endpoints included (by RECIST v1.1) progression-free survival, overall response rate (ORR), duration of response (DoR), and safety. Results: Overall, 512 pts (median age: 62 years; range 35-86 years) from 132 sites in 10 countries in Asia (404 pts [79%]), Europe, and North America (108 pts [21%]) were randomized to tisle (n=256) or ICC (n=256) (ITT population). Of these, 157 pts (tisle [n=89], ICC [n=68]) had vCPS ≥10% (PD-L1+ population). On 1 Dec 2020 (data cut-off), median follow-up was 8.5 months (m) with tisle and 5.8 m with ICC. The study met its primary endpoint: tisle clinically and significantly improved OS vs ICC in the ITT population (median OS: 8.6 vs 6.3 m; HR 0.70, 95% CI 0.57-0.85, p=0.0001). Tisle also demonstrated significant improvement in OS vs ICC in the PD-L1+ population (median OS: 10.3 vs 6.8 m; HR 0.54, 95% CI: 0.36-0.79, p=0.0006). Survival benefit was consistently observed across pre-defined subgroups, including baseline PD-L1 status and region. Treatment with tisle was also associated with a higher ORR (20.3% vs 9.8%) and more durable response (median DoR: 7.1 vs 4.0 m; HR 0.42, 95% CI 0.23-0.75) than ICC in the ITT population. Fewer pts had ≥Grade 3 (46% vs 68%) treatment-emergent adverse events with tisle vs ICC. Of these, fewer ≥Grade 3 AEs were treatment-related (TR) with tisle vs ICC (19% vs 56%). Fewer pts discontinued tisle vs ICC (7% vs 14%) due to a TRAE. Conclusion: Tisle demonstrated statistically significant and clinically meaningful improvement in OS vs ICC in pts with advanced or metastatic ESCC who had disease progression during or after first-line systemic therapy. Tisle showed a higher and longer response vs ICC. The safety profile of tisle was more favorable than ICC. Clinical trial information: NCT03430843.

Anlotinib plus docetaxel versus docetaxel as second-line treatment for advanced non-small cell lung cancer (NSCLC): Updated results from a phase I/II study.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e21055-e21055
Author(s):  
Yong Fang ◽  
Hongming Pan ◽  
Jiawei Shou ◽  
Wei Hong ◽  
Qunyi Guo ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Phase I ◽  
Safety Profile ◽  
Advanced Nsclc ◽  
Phase Ii Study ◽  
Line Treatment ◽  
Second Line ◽  
Grade 3 ◽  
Ecog Ps

e21055 Background: Second-line chemotherapy alone, such as docetaxel, is standard of care for patients (pts) with advanced NSCLC, but the efficacy is poor. Anti-angiogenic drugs plus chemotherapy had shown to significantly prolong progression-free survival (PFS) in advanced NSCLC (REVEL and LUME-LUNG1). The REVEL trial had demonstrated that East Asian pts with advanced NSCLC receiving docetaxel (60 mg/m2, not 75mg/m2) and ramucirumab had a better safety profile. Anlotinib, a novel oral multitarget tyrosine kinase inhibitor, significantly improved PFS and overall survival (OS) of advanced NSCLC in the ALTER0303 trial. In the phase I study, 10mg (QD, d1 to 14 of a 21-day cycle) was identified as the maximum tolerated dose (MTD) of anlotinib when combined with docetaxel (60mg/m2) by a 3+3 dose de-escalation exploration. Here, we presented the updated efficacy and safety of anlotinib plus docetaxel versus docetaxel as second-line treatment for driver-negative advanced NSCLC in the phase II study. Methods: This open-label, multicenter, randomized phase II study enrolled advanced NSCLC pts who had progressed after first-line platinum-based chemotherapy, without sensitizing EGFR/ALK/ROS1 alterations, and with ECOG PS 0-1. Eligible pts were randomized 2:1 to receive anlotinib (10mg, p.o, QD, d1 to 14 of a 21-day cycle) plus docetaxel (60mg/m2, q3w, 4-6 cycles) (A+D arm) or docetaxel (60mg/m2, q3w, 4-6 cycles) alone (D arm) until disease progression or unacceptable toxicity. The primary endpoint was PFS. Secondary endpoints included the objective response rate (ORR), the disease control rate (DCR), OS and safety. Results: From Jun. 2019 to Dec. 2020, 36 pts were enrolled, 24 pts (median age: 63.0, squamous cell carcinoma: 50.0%, ECOG PS 1: 87.5%) in the A+D arm and 12 pts (median age: 60.0, squamous cell carcinoma: 50.0%, ECOG PS 1: 83.3%) in the D arm. As of Jan. 20, 2021, the median PFS were 6.2 months (95% Cl: 0.00-12.82) in the A+D arm vs 1.4 months (95% Cl: 0.71-2.09) in the D arm (HR: 0.30; 95% Cl: 0.11-0.78, p = 0.007), which remain immature because of the shorter follow-up time. The median OS was not reached. For tumor response, 32 pts were evaluable. The ORR was 27.3% in the A+D arm vs 0% in the D arm (p = 0.142), and the A+D arm showed a significantly higher DCR than the D arm (100.0% vs 50.0%, p = 0.001). Grade 3/4 treatment-related adverse events (TRAEs) occurred in 33.3% (A+D arm) and 0.0% (D arm). The most commonly reported grade 3/4 TRAEs in the A+D arm included neutropenia (8.3%, 2/24), leukopenia (8.3%, 2/24), oral mucositis (8.3%, 2/24) and hypertension (8.3%, 2/24). No grade 5 TRAEs or deaths were observed. Conclusions: Anlotinib plus docetaxel continues to show the better clinical benefit as second-line treatment for driver-negative advanced NSCLC. The safety profile was manageable and consistent with previously reported studies. The longer follow-up time is required. Clinical trial information: NCT03726736.

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