scholarly journals Neoadjuvant Therapy in Lung Cancer: What Is Most Important: Objective Response Rate or Major Pathological Response?

2021 ◽  
Vol 28 (5) ◽  
pp. 4129-4138
Author(s):  
Xi Chen ◽  
Kewei Ma
Keyword(s):  
Lung Cancer ◽  
Neoadjuvant Therapy ◽  
Response Rate ◽  
Objective Response ◽  
Research Progress ◽  
Evaluation Standards ◽  
Therapeutic Alternatives ◽  
Cure Rates ◽  
Important Objective

Lung cancer is the most fatal and frequently diagnosed malignant tumor. Neoadjuvant therapy is a promising approach for prolonging survival and increasing the chance of cure rates for patients with potentially resectable disease. Currently, many therapeutic alternatives, including chemotherapy, targeted therapy, and immunotherapy, are continually being explored to enrich the content of neoadjuvant therapy. However, neoadjuvant therapy remains to have no unified evaluation standards. Overall survival (OS) is the “gold standard” for evaluating the clinical benefit of cancer treatment, but it needs years for a reliable evaluation. Hence, researchers need to identify surrogate endpoints that can predict OS accurately and reliably without long follow-up periods. In this review, we describe the research progress of different neoadjuvant therapies and explore their response evaluation, aiming to identify stronger predictors of OS.

Phase II study of docetaxel and cisplatin in advanced non-small-cell lung cancer.

1998 ◽  
Vol 16 (5) ◽  
pp. 1948-1953 ◽  
Author(s):  
J Zalcberg ◽  
M Millward ◽  
J Bishop ◽  
M McKeage ◽  
A Zimet ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Phase Ii ◽  
Advanced Nsclc ◽  
Response Rate ◽  
Phase Ii Study ◽  
Performance Status ◽  
Objective Response ◽  
Small Cell ◽  
Small Cell Lung ◽  
Grade 3

PURPOSE Docetaxel (Taxotere, Rhone-Poulenc Rorer, Antony, France) and cisplatin are two of the most active single agents used in the treatment of non-small-cell lung cancer (NSCLC). A recently reported phase I study of the combination of docetaxel and cisplatin recommended a dose of 75 mg/m2 of both drugs every 3 weeks for subsequent phase II study. PATIENTS AND METHODS Eligible patients were aged 18 to 75 years with a World Health Organization (WHO) performance status < or = 2 and life expectancy > or = 12 weeks, with metastatic and/or locally advanced NSCLC proven histologically or cytologically. Patients were not permitted to have received prior chemotherapy, extensive radiotherapy, or any radiotherapy to the target lesion and must have had measurable disease. Concurrent treatment with colony-stimulating factors (CSFs) or prophylactic antibiotics was not permitted. Docetaxel (75 mg/m2) in 250 mL 5% dextrose was given intravenously (i.v.) over 1 hour immediately before cisplatin (75 mg/m2) in 500 mL normal saline given i.v. over 1 hour in 3-week cycles. Premedication included ondansetron, dexamethasone, promethazine, and standard hyperhydration with magnesium supplementation. RESULTS A total of 47 patients, two thirds of whom had metastatic disease, were entered onto this phase II study. The majority of patients were male (72%) and of good (WHO 0 to 1) performance status (85%). All 47 patients were assessable for toxicity and 36 were for response. Three patients were ineligible and eight (17%) discontinued treatment because of significant toxicity. In assessable patients, the overall objective response rate was 38.9% (95% confidence limits [CL], 23.1% to 56.5%), 36.1% had stable disease, and 25% progressive disease. On an intention-to-treat analysis, the objective response rate was 29.8%. Median survival was 9.6 months and estimated 1-year survival was 33%. Significant (grade 3/4) toxicities included nausea (26%), hypotension (15%), diarrhea (13%), and dyspnea mainly related to chest infection (13%). One patient experienced National Cancer Institute (NCI) grade 3 neurosensory toxicity after eight cycles. Grade 3/4 neutropenia was common and occurred in 87% of patients, but thrombocytopenia > or = grade 3 was rare (one patient). Significant (grade 3/4) abnormalities of magnesium levels were common (24%). Febrile neutropenia occurred in 13% of patients and neutropenic infection in 11%, contributing to two treatment-related deaths. No neutropenic enterocolitis or severe fluid retention was reported. CONCLUSION Compared with other active regimens used in this setting, the combination of docetaxel and cisplatin in advanced NSCLC is an active regimen with a similar toxicity profile to other combination regimens.

Randomized, Double-Blind, Placebo-Controlled, Multicenter Phase II Study of Fruquintinib After Two Prior Chemotherapy Regimens in Chinese Patients With Advanced Nonsquamous Non‒Small-Cell Lung Cancer

2018 ◽  
Vol 36 (12) ◽  
pp. 1207-1217 ◽  
Author(s):  
Shun Lu ◽  
Jianhua Chang ◽  
Xiaoqing Liu ◽  
Jianhua Shi ◽  
You Lu ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Growth Factor ◽  
Objective Response Rate ◽  
Response Rate ◽  
Objective Response ◽  
Small Cell ◽  
Small Cell Lung ◽  
Double Blind ◽  
Double Blind Placebo ◽  
Multicenter Phase

Purpose Patients with advanced non‒small-cell lung cancer (NSCLC) who fail two lines of chemotherapy have unmet medical needs. The kinase inhibitor fruquintinib selectively targets vascular endothelial growth factor receptors and, hence, tumor angiogenesis and lymphogenesis. This randomized, double-blind, placebo-controlled, multicenter phase II trial evaluated the efficacy and safety of fruquintinib in patients with advanced nonsquamous NSCLC who experienced disease progression after second-line chemotherapy. Patients and Methods Eligible patients were randomly assigned (two to one; stratified by epidermal growth factor receptor status) to receive fruquintinib or placebo, both in combination with best supportive care. Oral fruquintinib (5 mg once daily) was given in 4-week cycles of 3 weeks of treatment followed by 1 week off. Tumor response was assessed using Response Evaluation Criteria in Solid Tumors version 1.1. The primary end point was progression-free survival (PFS) evaluated by a blinded image central review (BICR) committee. Secondary end points included investigator-evaluated PFS, objective response rate, disease control rate, overall survival, and safety. Results Ninety-one patients from 12 hospitals received treatment with fruquintinib (n = 61) or placebo (n = 30). Median PFS was 3.8 months with fruquintinib by both BICR and investigators’ evaluations (hazard ratio by BICR, 0.34; 95% CI, 0.20 to 0.57; P < .001). Three- and 6-month survival rates were 90.2% and 67.2% in the fruquintinib group and 73.3% and 58.8% in the placebo group, respectively. The objective response rate and disease control rate were 13.1% and 60.7% with fruquintinib, compared with 0% and 13.3% with placebo ( P = .041 and < .001), respectively. The most common treatment-emergent adverse events with fruquintinib (≥ grade 3) were hypertension (8.2%), hand-foot syndrome (4.9%), and proteinuria (4.9%). Conclusion Third- and fourth-line fruquintinib for advanced NSCLC was superior to placebo and had an acceptable safety profile.

Tailored immunotherapy approach with nivolumab in advanced transitional cell carcinoma (TITAN-TCC).

2021 ◽  
Vol 39 (6_suppl) ◽  
pp. 446-446
Author(s):  
Marc-Oliver Grimm ◽  
Bernd Schmitz-Dräger ◽  
Uwe Zimmermann ◽  
Barbara Grün ◽  
Gustavo Bruno Baretton ◽  
...  
Keyword(s):  
Immune Checkpoint ◽  
Response Rate ◽  
Checkpoint Inhibitors ◽  
Objective Response ◽  
Transitional Cell ◽  
Added Value ◽  
Phase Iii ◽  
First Line ◽  
Third Line

446 Background: Several PD-1 immune-checkpoint inhibitors including Nivolumab (Nivo) are approved in urothelial cancer. Recently, in the front line setting, improved activity of combined PD-L1 and CTLA4 immune-checkpoint inhibition has been reported and a phase III trial with Nivolumab + Ipilimumab (Nivo+Ipi) is ongoing. Here we report a response-based tailored approach starting treatment with Nivo monotherapy using Nivo+Ipi as immunotherapeutic “boost”. Methods: Between July 2017 and April 2019 86 patients were enrolled and treated according to protocol version 3 (cohort 1). Patients started with Nivo 240 mg Q2W induction. After 4 dosings and tumor assessment at week 8 (i) responders (PR/CR) to Nivo monotherapy continued with maintenance while (ii) patients with stable (SD) or progressive disease (PD) received 2 cycles Nivo3+Ipi1 followed by another 2 cycles Nivo1+Ipi3 if not responding. Median follow-up is 8.7 months. The primary endpoint is confirmed investigator-assessed objective response rate (ORR) per RECIST1.1. Secondary endpoints include activity of Nivo monotherapy at week 8, remission rate with Nivo+Ipi “boosts”, safety, overall survival and quality of life. Results: Of the patients 42, 39 and 5 were first, second and third line, respectively. Median age was 67 years (range 45-84), 61 patients (71 %) were male and 25 female. ORR with Nivo monotherapy at first assessment (week 8) was 29 % and 23 % in first and second/third line, respectively. Of the patients 41 received Nivo+Ipi “boosts” after week 8 while 12 received later “boosts”. Best overall response (BOR) rate with Nivo induction ± Nivo+Ipi “boosts” was 48 % and 27 % in first and second/third line, respectively. In first line 7/17 (41 %) patients receiving Nivo+Ipi after week 8 had an improved response compared to 2/24 (8.3 %) in second/third line. Of the patients who continued with Nivo maintenance after week 8 and received later “boosts” 2/12 (17 %) had a PR and 2/12 (17 %) improved to SD. Treatment-related AEs will be presented. Conclusions: TITAN–TCC explores a response-driven use of Nivo+Ipi as an immunotherapeutic “boost”. In first line, this significantly improved ORR compared to the expected response rate of Nivo monotherapy, providing further evidence to the added value of Ipi in combination with Nivo. Further follow-up is ongoing to characterize duration and depth of response. Clinical trial information: NCT03219775 . Research Sponsor: Bristol-Myers Squibb[Table: see text]

Phase III randomized trial comparing cisplatin and carboplatin with or without ifosfamide in patients with advanced non-small-cell lung cancer. European Lung Cancer Working Party.

1998 ◽  
Vol 16 (4) ◽  
pp. 1388-1396 ◽  
Author(s):  
J P Sculier ◽  
M Paesmans ◽  
J Thiriaux ◽  
J Lecomte ◽  
G Bureau ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Randomized Trial ◽  
Cell Lung Cancer ◽  
Response Rate ◽  
Objective Response ◽  
Small Cell ◽  
Phase Iii ◽  
Small Cell Lung ◽  
Moderate Dose

PURPOSE A phase III randomized trial in patients with advanced non-small-cell lung cancer (NSCLC) was performed to determine if the addition of ifosfamide to moderate-dose cisplatin and carboplatin improved response rate (primary end point) and survival. PATIENTS AND METHODS A total of 529 patients were randomized to receive a combination of moderate-dose carboplatin (200 mg/m2 intravenously [i.v.] on day 1) and cisplatin (30 mg/m2 i.v. on days 2 and 3) with (CCI arm) or without (CC arm) ifosfamide (1.5 g/m2 i.v. on days 1 to 3). There were 248 eligible patients on the CC arm and 257 on the CCI arm, with 220 and 238 patients assessable for response, respectively. All but 23 had stage IV disease with pleural effusion. RESULTS There was a 16% objective response (OR) rate to CC and a 31% OR rate to CCI. That observed difference was highly statistically significant (P < 0.001). Duration of response and survival were not statistically different between arms. The CCI regimen was associated with significantly more acute toxicities: emesis, alopecia, leukopenia, and thrombocytopenia. The frequency of chronic renal, auditive, and peripheral neurologic toxicity was low in both arms (4.6% and 6.6%, respectively, after six courses of chemotherapy). The relative dose-intensity (RDI) of the CCI arm was significantly lower than that of the CC arm. CONCLUSION The addition of ifosfamide to moderate-dose cisplatin and carboplatin significantly improves the antitumoral response rate, but has no apparent effect an survival in advanced NSCLC.

scholarly journals Disodium Cantharidinate and Vitamin B6 Injection Adjunct with Platinum-Based Chemotherapy for the Treatment of Advanced Non-Small-Cell Lung Cancer: A Meta-Analysis

2019 ◽  
Vol 2019 ◽  
pp. 1-14 ◽  
Author(s):  
Zhichao Wang ◽  
Fanchao Feng ◽  
Qi Wu ◽  
Yihan Jin ◽  
Cheng Gu ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Objective Response Rate ◽  
Vitamin B6 ◽  
Response Rate ◽  
Meta Analysis ◽  
Objective Response ◽  
Small Cell ◽  
Karnofsky Performance Score ◽  
Performance Score ◽  
Small Cell Lung

Purpose. Disodium cantharidinate and vitamin B6 (DCVB6) injection is effective and widely used for the clinical treatment of non-small-cell lung cancer (NSCLC). This meta-analysis aimed to provide evidence-based medical data for clinical treatment with DCVB6 injection. Methods. We searched 7 medical databases up to January 2018 for all randomized controlled trials (RCTs) based on DCVB6 injection combined with chemotherapy in patients with NSCLC. A manual search in relevant journals and of relevant literature on other websites was also performed. Data extraction and quality assessment were conducted independently by two reviewers. Subsequently, a meta-analysis was conducted using RevMan 5.3 software. Pooled risk ratio (RR) with 95% confidence interval (CI) was used to evaluate dichotomous and continuous outcomes, respectively. The PROSPERO ID was CRD42018086377. Results. A total of 19 RCTs were included. The results of the meta-analysis indicated that the DCVB6 injection combined with chemotherapy was superior to chemotherapy alone regarding objective response rate (RR=1.58, 95% CI 1.40-1.79), Karnofsky performance score (RR=1.68, 95% CI 1.42-1.99), clinical symptom (RR=1.68, 95% CI 1.44-1.96), white blood cell toxicity (RR=0.36, 95% CI 0.27-0.49), platelet toxicity (RR=0.46, 95% CI 0.33-0.63), and vomiting (RR=0.50, 95% CI 0.37-0.67). Conclusions. The current evidence suggests that DCVB6 injection combined with chemotherapy could increase objective response rate and Karnofsky performance score, improve clinical symptoms, and reduce side effects caused by chemotherapy in patients with NSCLC. However, these results should be carefully interpreted due to the low-quality methodology and the small sample sizes of the trials, and our conclusions should be verified by high-quality, large-scale, double-blinded RCTs.

Randomized trial of three combinations of cisplatin with vindesine and/or VP-16-213 in the treatment of advanced non-small-cell lung cancer.

1985 ◽  
Vol 3 (2) ◽  
pp. 176-183 ◽  
Author(s):  
H M Dhingra ◽  
M Valdivieso ◽  
D T Carr ◽  
D F Chiuten ◽  
P Farha ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Median Survival ◽  
Cell Lung Cancer ◽  
Response Rate ◽  
Small Cell ◽  
High Dose ◽  
Small Cell Lung ◽  
To Receive

One hundred sixty-seven evaluable patients with non-small-cell lung cancer were randomized to receive high-dose cisplatin and vindesine (PVD), or cisplatin and VP-16-213 (etoposide epipodophyllotoxin) (PVP), or cisplatin with VP-16-213 and vindesine (PVPVD). The patient distribution and characteristics were similar in all the treatment arms. The response rate differences (35% in PVD arm, 30% in PVP arm, and 22% in PVPVD arm) were not statistically significant (P = .33). Response durations were 43 weeks in the PVD arm, 20 weeks in the PVP arm, and 27 weeks in the PVPVD arm. Median survival was 29 weeks in the PVD and PVP arms and 28 weeks in the PVPVD arm. Median survival time of responding patients was 76 weeks in the PVD arm and 65 weeks in the PVP arm; 78% of patients were alive at 22+ to 87+ weeks follow-up in the PVPVD arm. Myelosuppression was similar in all three treatment arms. Significantly more azotemia occurred in the PVD arm than in the PVP and PVPVD arms (P = .002), and significantly more neuropathy in the PVD and PVPVD arms than in the PVP arm (P = .003 and .005). All the treatment arms have similar antitumor activity in non-small-cell lung cancer, but the PVP combination is slightly less toxic than the PVD and PVPVD treatment arms.

Combination therapy with interferon alfa-2a and interleukin-2 for the treatment of metastatic cancer.

1995 ◽  
Vol 13 (5) ◽  
pp. 1110-1122 ◽  
Author(s):  
F M Marincola ◽  
D E White ◽  
A P Wise ◽  
S A Rosenberg
Keyword(s):  
Response Rate ◽  
Metastatic Cancer ◽  
Objective Response ◽  
Interleukin 2 ◽  
Interferon Alfa ◽  
Group 4 ◽  
Ifn Alpha ◽  
Group 5 ◽  
Group 2

PURPOSE Here we report the long-term follow-up evaluation of a phase I/II study of toxicity and response of combination interferon alfa-2a (IFN alpha) and interleukin-2 (IL-2) in patients with metastatic cancer. PATIENTS AND METHODS From November 1987 through October 1990, 189 patients were treated with 379 courses. IFN alpha (3 x 10(6) U/m2) was administered three times per day as an intravenous (IV) bolus with IV IL-2 2.6 x 10(6) IU/m2 (six patients, group 1), 7.8 x 10(6) IU/m2 (32 patients, group 2), or 11.7 x 10(6) IU/m2 (26 patients, group 3). Subsequently, IFN alpha dose was escalated to 6 x 10(6) U/m2 plus IL-2 11.7 x 10(6) IU/m2 (22 patients, group 4). Two further dosage schedules of IL-2 were tested at 7.8 x 10(6) IU/m2 (29 patients, group 5) and 15.6 x 10(6) IU/m2 (74 patients, group 6); however, because of IFN alpha-related toxicity, these two groups received IFN alpha once per day (6 x 10(6) U/m2). A treatment course consisted of two cycles (maximum, 15 doses per cycle) separated by a 10-day interval. RESULTS All patients were assessable for response: 82 patients had melanoma, 75 renal cell carcinoma (RCC), and 16 colorectal cancer. There were two treatment-related deaths. The objective response rate was 23% (43 patients). Response rates were 17%, 19%, 19%, 32%, 41%, and 16%, respectively, for groups 1 through 6. Ten responses are still ongoing (nine in RCC patients) at 57 to 74 months, and 21 patients are alive, for an overall 5-year survival rate of 11%. The median potential follow-up period was 65 months. Although a significantly higher response rate was noted for group 4 (highest dose of IFN alpha three times per day), no benefit for survival and increased toxicity were noted in this group. CONCLUSION Based on these findings, we conclude that further studies of this combination treatment are not warranted.

Randomized study of vinorelbine and cisplatin versus vindesine and cisplatin versus vinorelbine alone in advanced non-small-cell lung cancer: results of a European multicenter trial including 612 patients.

1994 ◽  
Vol 12 (2) ◽  
pp. 360-367 ◽  
Author(s):  
T Le Chevalier ◽  
D Brisgand ◽  
J Y Douillard ◽  
J L Pujol ◽  
V Alberola ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Response Rate ◽  
Randomized Study ◽  
Objective Response ◽  
Multicenter Trial ◽  
Small Cell ◽  
Survival Duration ◽  
Small Cell Lung

PURPOSE We designed a prospective randomized trial to compare vinorelbine and cisplatin (NVB-P) with vindesine and cisplatin (VDS-P) and to evaluate whether the best of these regimens affords a survival benefit compared with vinorelbine alone (NVB), an outpatient regimen, in patients with non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS Forty-five centers included 612 patients in this study: 206 on NVB-P, 200 on VDS-P, and 206 on NVB. Vinorelbine was administered at a dose of 30 mg/m2 weekly, cisplatin at 120 mg/m2 on days 1 and 29 and then every 6 weeks, and vindesine at 3 mg/m2 weekly for 6 weeks and then every other week. Treatment was continued until progression or toxicity. Four percent of the patients entered were ineligible and 59% had metastatic disease. RESULTS An objective response rate was observed in 30% of patients in the NVB-P arm versus 19% in the VDS-P arm (P = .02) and 14% in the NVB arm (P < .001). The median duration of survival was 40 weeks in the NVB-P arm, compared with 32 weeks in the VDS-P arm and 31 weeks in the NVB arm. Comparison of survival among the three groups demonstrated an advantage for NVB-P compared with VDS-P (P = .04) and NVB (P = .01). Neutropenia was significantly higher in the NVB-P group (P < .001), and neurotoxicity was more frequent with VDS-P (P < .004). CONCLUSION Since our results have demonstrated that NVB-P yields a longer survival duration and a higher response rate than VDS-P or NVB alone, with acceptable toxicity, this combination should be considered a relevant regimen in advanced NSCLC.

ALK and EGFR mutation analysis in a phase II trial of cisplatin/pemetrexed in Japanese patients with advanced nonsquamous non-small cell lung cancer.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e18017-e18017
Author(s):  
Kyohei Kaburaki ◽  
Fumiyoshi Ohyanagi ◽  
Azusa Tanimoto ◽  
Toshio Sakatani ◽  
Yuko Kawano ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Egfr Mutation ◽  
Response Rate ◽  
Fusion Gene ◽  
Objective Response ◽  
Small Cell ◽  
Wild Type ◽  
Small Cell Lung

e18017 Background: Recently, ethnic differences and genotypes such as EGFR mutation (EGFRm) or fusion gene (ALK translocation: ALKt) are important factors in non-small cell lung cancer (NSCLC) treatment. Pemetrexed (P)/cisplatin (C) is one of the standard care for advanced non-squamous (Nsq) NSCLC. However, the efficacy of the CP regimen has not been well examined in Japanese Nsq NSCLC patients (pts); furthermore, the difference in efficacy between genotypes was not thoroughly examined. Therefore, the present study was conducted to evaluate the efficacy of the CP regimen in Japanese Nsq NSCLC pts, and to determine whether EGFRm and ALKt impacted the treatment. Methods: This study was conducted from May 2009 to December 2010. Pts were eligible for this study if they had histologically or cytologically confirmed recurrent or metastatic Nsq NSCLC previously untreated with chemotherapy, an ECOG performance status of 0 or 1, life expectancy of more than 12 weeks, and adequate organ function. Pts received C (75 mg/m2) plus P (500 mg/m2) on day 1 every 3 weeks. Of the 50 pts initially enrolled, 49 were evaluated, and 43 tumor samples were available for analysis. Most pts were male (80%), and 80% of the pts had adenocarcinoma. The primary endpoint was the response rate that was evaluated according to RECIST. EGFRm was examined using PCR-based methods, and the ALK fusion protein was examined using a highly sensitive IHC method in the available tumor specimens. Although the CP regimen demonstrates consistent efficacy in Japanese Nsq NSCLC pts, EGFRm and ALKt may have impacted this treatment. Results: The objective response rate and disease control rate in all pts were 44.9% and 79.6%, respectively. The median progression-free survival was 4.4 months, and the 1-year survival was 73.5%. Toxicities were mild; no new toxicity profile was identified. Among the 43 samples, the following mutations were identified: 9 EGFRm (21%), 5 ALKt (12%), and 29 wild-type (67%). Objective response was observed in 6 (66.7%) EGFRm, 2 (40%) ALKt, and 13 (44.8%) wild-type. Conclusions: Although the CP regimen demonstrates consistent efficacy in Japanese Nsq NSCLC pts, EGFRm and ALKt may have impacted this treatment.

First-line (1L) avelumab treatment in patients (pts) with metastatic Merkel cell carcinoma (mMCC): Preliminary data from an ongoing study.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 9530-9530 ◽  
Author(s):  
Sandra P. D'Angelo ◽  
Jeffrey Russell ◽  
Jessica Cecile Hassel ◽  
Celeste Lebbe ◽  
Bartosz Chmielowski ◽  
...  
Keyword(s):  
Safety Profile ◽  
Response Rate ◽  
Objective Response ◽  
Durable Response ◽  
Phase 2 Study ◽  
Grade 3 ◽  
Related Reaction ◽  
Unacceptable Toxicity ◽  
Clinical Trial Information

9530 Background: MCC is a rare, aggressive skin cancer. Avelumab is a fully human anti–PD-L1 antibody. In a phase 2 study in pts with distant mMCC who progressed after prior chemotherapy (JAVELIN Merkel 200; NCT02155647), avelumab showed a manageable safety profile and durable responses, including an objective response rate (ORR) of 31.8%, estimated 6-month durable response rate of 29%, and 6-month overall survival rate of 69%. Here, we report preliminary results from a separate cohort of pts with chemotherapy-naïve mMCC enrolled in the same study. Methods: Eligible pts with mMCC and no prior systemic treatment for metastatic disease received avelumab 10 mg/kg Q2W until confirmed progression, unacceptable toxicity, or withdrawal. Tumors were assessed every 6 weeks (RECIST v1.1). Adverse events (AEs) were assessed by NCI CTCAE v4.0. Results: As of Dec 30, 2016, 29/112 planned pts had been enrolled. Median age was 75.0 years (range 47–87). Median treatment duration was 8.1 weeks (range 2.0–37.9). Of 16 pts with ≥3 months of follow-up, unconfirmed ORR was 68.8% (95% CI 41.3–89.0) with CR in 18.8%; confirmed ORR was 56.3% (95% CI 29.9–80.2; 1 unconfirmed PR with discontinuation). Of 25 pts with ≥6 weeks of follow-up, unconfirmed ORR was 64.0% (95% CI 42.5–82.0). All responses were ongoing at last follow-up, including in 5/5 pts with ≥6 months of follow-up (potential to confirm responses). 20/29 pts (69.0%) had a treatment-related AE (TRAE), including grade 3–4 TRAE in 5 pts (17.2%). TRAEs led to discontinuation in 5 pts (17.2%): 2 pts with infusion-related reaction, and 1 pt each with elevated AST and ALT, cholangitis, and paraneoplastic syndrome. There were no treatment-related deaths. 21/29 pts (72.4%) remain on treatment. Conclusions: In initial results from a cohort of chemotherapy-naïve pts with mMCC, avelumab was associated with early responses and a manageable safety profile, consistent with findings for second-line or later avelumab treatment in a previous cohort. These results suggest that responses mature to become durable and the use of 1L avelumab may increase the probability of response vs later-line treatment. Enrollment and follow-up in this 1L cohort are ongoing. Clinical trial information: NCT02155647.

Sign in / Sign up

Export Citation Format

Share Document