Abstract 3462
Background
Tyrosine kinase inhibitors (TKI) and nivolumab (NIVO) are key components of systemic therapies in metastatic renal cell carcinoma (mRCC). We tested if TKI induction followed by an early switch to NIVO improved outcome in mRCC.
Methods
Key inclusion criteria were measurable advanced or metastatic ccRCC, ECOG PS 0-2, adequate organ function, and PR or SD after sunitinib (50 mg, 4-2 regime) or pazopanib (800 mg OD) for 10-12 weeks. 1:1 randomized to either continue TKI treatment or receive nivolumab 240 or 480 mg IV q2-4wks, until PD or intolerance. Imaging occurred q12wks and health-related quality of life (HR-QoL) was assessed monthly x3 and q12wks thereafter (FKSI-15). Primary and key secondary endpoints were survival rate at 2 years and ORR, respectively. The trial stopped prematurely for low accrual after 49 of 244 patients were randomized.
Results
25 and 24 pts. were randomized to receive NIVO or TKI continuation, respectively. Median age was 65 years (range: 35-79), 40 pts. (82%) were male and 2 pts. (4%) had an ECOG PS of 2. MSKCC risk categories: favorable, intermediate, poor were (n; %): 15 (31), 32 (65) and 2 (4). Pazopanib was used in 22 (45). Response to TKI induction was PR in 29 (59) and SD in 20 (41). In the ITT population, best overall response rate measured from start of induction therapy was not significantly different for NIVO vs. TKI (64 vs. 70%, P = 0.76). However, when measured from time of randomization, ORR for NIVO vs. TKI was 16 vs. 48% (P = 0.029). Adverse events (AE) for NIVO vs. TKI occurred in 96% vs. 100% (all grades) and 44% vs. 67% (grades 3-5), respectively. Serious AE (SAE) for NIVO vs. TKI continuation were reported in 10 (40) and 9 (38), respectively.Table:
959P Best overall response to nivolumab or TKI treatment (ITT population)
From start of TKI induction | From randomization | |||||
---|---|---|---|---|---|---|
Category | NIVO | TKI | Total | NIVO | TKI | Total |
n | 25 | 23 | 48 | 25 | 23 | 48 |
CR | -- | 1 (4%) | 1 (2%) | -- | 1 (4%) | 1 (2%) |
PR | 16 (64%) | 15 (65%) | 31 (65%) | 4 (16%) | 10 (43%) | 14 (29) |
SD | 9 (36%) | 7 (30%) | 16 (33%) | 6 (24%) | 7 (30%) | 13 (27%) |
PD | -- | -- | -- | 11 (44%) | 3 (13%) | 14 (29%) |
NE | -- | -- | -- | 4 (16%) | 2 (9%) | 6 (12%) |
Conclusions
TKI induction followed by early switch to NIVO did not improve ORR in patients responsive to TKI. These results do not support the notion that TKI pretreatment sensitizes for nivolumab efficacy. Major limitations of our trial are the premature closure and the limited sample size.
Clinical trial identification
2016-002170-13; NCT02959554.
Editorial acknowledgement
Legal entity responsible for the study
AIO-Studien-gGmbH, Berlin.
Funding
Bristol-Myers Squibb.
Disclosure
V. Grünwald: Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self), Shareholder / Stockholder / Stock options: BMS; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self): Ipsen; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self): Eisai; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self): Novartis; Research grant / Funding (self): Pfizer; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self), Shareholder / Stockholder / Stock options: AstraZeneca; Advisory / Consultancy: Bayer; Advisory / Consultancy, Speaker Bureau / Expert testimony: Cerulean; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self): Roche; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self), Shareholder / Stockholder / Stock options: MSD; Advisory / Consultancy, Speaker Bureau / Expert testimony: Art tempi; Advisory / Consultancy, Speaker Bureau / Expert testimony: Astellas; Advisory / Consultancy, Speaker Bureau / Expert testimony: COCS; Advisory / Consultancy, Speaker Bureau / Expert testimony: ClinSol; Advisory / Consultancy, Speaker Bureau / Expert testimony: EUSAPharm; Advisory / Consultancy, Speaker Bureau / Expert testimony: MedUpdate; Advisory / Consultancy, Speaker Bureau / Expert testimony: Merck Serono; Advisory / Consultancy, Speaker Bureau / Expert testimony: MedKomAkademie; Advisory / Consultancy, Speaker Bureau / Expert testimony: NewConceptOncology; Advisory / Consultancy, Speaker Bureau / Expert testimony: Lilly; Advisory / Consultancy, Speaker Bureau / Expert testimony: Johnson & Johnson; Advisory / Consultancy, Speaker Bureau / Expert testimony: PharmaMar; Advisory / Consultancy, Speaker Bureau / Expert testimony: PeerVoice; Advisory / Consultancy, Speaker Bureau / Expert testimony: StreamedUp!; Advisory / Consultancy, Speaker Bureau / Expert testimony: ThinkWired!. All other authors have declared no conflicts of interest.
Resources from the same session
2929 - Changes of the Commensal Microbiome during Treatment are Associated with Clinical Response in the Nasopharyngeal Carcinoma Patients
Presenter: Tingting Huang
Session: Poster Display session 3
Resources:
Abstract
2888 - Development and validation a nomogram based on pathological microscopic features to predict survival in nasopharyngeal carcinoma and guide treatment decision
Presenter: Kuiyuan Liu
Session: Poster Display session 3
Resources:
Abstract
3607 - Deep learning in nasopharyngeal carcinoma: a retrospective cohort study of 3D convolutional neural networks on magnetic resonance imaging
Presenter: Meng Yun Qiang
Session: Poster Display session 3
Resources:
Abstract
5848 - Combined androgen blockade in patients with advanced androgen receptor–positive salivary gland carcinoma: Exploratory biomarker analyses
Presenter: Chihiro Fushimi
Session: Poster Display session 3
Resources:
Abstract
4484 - Classification of esthesioneuroblastoma (ENB) based on chromosome (chr) arm gain and loss (CNA) in the setting of a hypomutated genomic landscape
Presenter: Russell Madison
Session: Poster Display session 3
Resources:
Abstract
5753 - Trastuzumab plus docetaxel in patients with advanced HER2–positive salivary duct carcinoma: Exploratory biomarker analyses
Presenter: Hideaki Takahashi
Session: Poster Display session 3
Resources:
Abstract
3373 - Development and characterization of salivary gland cancer organoid cultures
Presenter: Wim Boxtel
Session: Poster Display session 3
Resources:
Abstract
3118 - A parent-of-origin effect of the RB1 mutations in retinoblastoma with low penetrance and variable expressivity
Presenter: Ekaterina Alekseeva
Session: Poster Display session 3
Resources:
Abstract
4512 - The humanistic burden reported by patients diagnosed with Recurrent/Metastatic Squamous Cell Carcinoma of the Head and Neck (R/M SCCHN) in Europe
Presenter: Prianka Singh
Session: Poster Display session 3
Resources:
Abstract
3961 - Concurrent Chemotherapy and External Radiation Therapy: An Open Label Non-Inferiority Phase III Randomized Controlled Trial of Weekly versus Three Weekly Cisplatin and Radical Radiotherapy in Locally Advanced Head and Neck Squamous Cell Carcinoma: CONCERT trial
Presenter: ATUL SHARMA
Session: Poster Display session 3
Resources:
Abstract