Abstract 3748
Background
Atezo, a monoclonal antibody targeting PD-L1, is an approved therapy for locally advanced/metastatic urothelial cancer. The pivotal IMvigor210 and IMvigor211 phase II and III trials excluded pts with significant pre-existing AID. The SAUL study (NCT02928406) in pts more representative of real-world practice showed median overall survival (OS) of 8.7 mo and safety consistent with previous atezo trials [Sternberg, Eur Urol 2019]. We analysed outcomes in pts with a history of AID.
Methods
Pts with locally advanced/metastatic urinary tract carcinoma, including pts ineligible for IMvigor211, received atezo 1200 mg q3w until loss of clinical benefit or unacceptable toxicity. The primary endpoint was safety, including adverse events of special interest (AESIs) for atezo as defined in the protocol. OS was a secondary endpoint. Subgroup analyses of AID pts were prespecified.
Results
Of 1004 pts enrolled from Nov 2016 to Mar 2018, 997 received atezo. In 35 pts presenting with AID, the most common pre-existing conditions were psoriasis (n = 15), thyroid AID (n = 5) and rheumatoid arthritis (n = 4). Compared with non-AID pts, AID pts had numerically more AESIs (46% vs 30%; grade ≥3 14% vs 6%) and treatment-related grade 3/4 AEs (26% vs 12%), but there were no relevant increases in treatment-related deaths (0% vs 1%) or AEs leading to atezo discontinuation (9% vs 6%). Pre-existing AID worsened in 6 pts: flares subsequently improved or resolved in 4 pts (without stopping atezo in 3 pts) but were unresolved in 2 pts (rash in 1 pt continuing atezo, psoriasis in 1 pt who discontinued atezo). In the 962 non-AID pts, new immune-related AEs were infrequent (6% hypothyroidism, 4% hyperthyroidism, 2% pneumonitis, 1% colitis). Efficacy was similar in AID vs non-AID pts (median OS 8.2 vs 8.8 mo, respectively; 1-year OS 31% vs 42%; disease control 51% vs 39%; median PFS 4.4 vs 2.2 mo).
Conclusions
In 35 atezo-treated pts with pre-existing AID, incidences of AESIs and treatment-related AEs appeared acceptable. AEs were manageable and rarely led to atezo discontinuation. Treating these pts requires caution but AID is not a barrier to atezo therapy per se.
Clinical trial identification
NCT02928406.
Editorial acknowledgement
Jennifer Kelly (Medi-Kelsey Ltd), funded by F Hoffmann-La Roche.
Legal entity responsible for the study
F Hoffmann-La Roche.
Funding
F Hoffmann-La Roche.
Disclosure
Y. Loriot: Honoraria (self), Honoraria (institution), Research grant / Funding (institution), Travel / Accommodation / Expenses: Roche; Honoraria (self), Honoraria (institution), Research grant / Funding (institution), Travel / Accommodation / Expenses: MSD; Honoraria (self), Honoraria (institution): Astellas; Honoraria (self), Honoraria (institution), Travel / Accommodation / Expenses: Janssen; Honoraria (self), Honoraria (institution), Travel / Accommodation / Expenses: AstraZeneca; Honoraria (self), Honoraria (institution): BMS; Honoraria (self), Honoraria (institution), Travel / Accommodation / Expenses: Seattle Genetics; Honoraria (self), Honoraria (institution), Research grant / Funding (institution): Sanofi; Honoraria (self), Honoraria (institution): Clovis; Honoraria (institution): Incyte; Honoraria (self), Honoraria (institution): Pfizer; Licensing / Royalties, Pending patent (USA 62/455211, Europe 17209098.7): n/a. C.N. Sternberg: Advisory / Consultancy: MSD; Advisory / Consultancy: Clovis; Advisory / Consultancy: Bristol-Myers Squibb; Advisory / Consultancy: Incyte; Advisory / Consultancy: AstraZeneca; Research grant / Funding (institution): Janssen; Research grant / Funding (institution): Roche; Research grant / Funding (institution): Bayer; Research grant / Funding (institution): Pfizer. D. Castellano Gauna: Advisory / Consultancy: Bayer; Advisory / Consultancy: Roche; Advisory / Consultancy: Astellas; Advisory / Consultancy: Janssen; Advisory / Consultancy: Sanofi; Advisory / Consultancy: Pfizer; Advisory / Consultancy: MSD; Advisory / Consultancy: Merck Serono; Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: BMS; Advisory / Consultancy: Ipsen; Advisory / Consultancy: Exelisis; Advisory / Consultancy: Lilly. H. Dumez: Advisory / Consultancy: Janssen; Advisory / Consultancy, Travel / Accommodation / Expenses: Sanofi; Advisory / Consultancy, Travel / Accommodation / Expenses: Astellas; Advisory / Consultancy, Travel / Accommodation / Expenses: Roche; Travel / Accommodation / Expenses: Novartis; Travel / Accommodation / Expenses: Bayer; Travel / Accommodation / Expenses: AstraZeneca; Travel / Accommodation / Expenses: Ipsen; Travel / Accommodation / Expenses: MSD; Travel / Accommodation / Expenses: Jansen-Cilag; Travel / Accommodation / Expenses: Pfizer. R. Huddart: Honoraria (self), Travel / Accommodation / Expenses: Janssen; Advisory / Consultancy, Research grant / Funding (self), Research grant / Funding (institution), Travel / Accommodation / Expenses: MSD; Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Roche; Advisory / Consultancy, Travel / Accommodation / Expenses: Nektar; Research grant / Funding (institution): Cancer Research UK. K.M. Vianna: Advisory / Consultancy, Speaker Bureau / Expert testimony: Lilly; Advisory / Consultancy: Novartis; Advisory / Consultancy: Bayer; Advisory / Consultancy: Pfizer; Speaker Bureau / Expert testimony: Roche; Speaker Bureau / Expert testimony: AstraZeneca; Speaker Bureau / Expert testimony: BMS. T. Alonso Gordoa: Advisory / Consultancy: BMS; Advisory / Consultancy: MSD; Advisory / Consultancy, Research grant / Funding (institution): Roche; Advisory / Consultancy, Speaker Bureau / Expert testimony: Astellas; Advisory / Consultancy, Speaker Bureau / Expert testimony: IPSEN; Advisory / Consultancy, Travel / Accommodation / Expenses: Sanofi; Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Pfizer; Speaker Bureau / Expert testimony: Janssen; Speaker Bureau / Expert testimony: Novartis. I.A. Skoneczna: Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Roche; Honoraria (self), Advisory / Consultancy: MSD; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Astellas; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution), Travel / Accommodation / Expenses: Bayer; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution), Travel / Accommodation / Expenses: Janssen; Honoraria (self), Research grant / Funding (institution), Travel / Accommodation / Expenses: AstraZeneca; Honoraria (self): Pfizer; Speaker Bureau / Expert testimony: IPSEN; Speaker Bureau / Expert testimony: BMS. A. Fay: Honoraria (self), Advisory / Consultancy: Pfizer; Honoraria (self), Advisory / Consultancy: Novartis; Honoraria (self): Bristol-Myers Squibb; Honoraria (self), Advisory / Consultancy: AstraZeneca; Honoraria (self), Advisory / Consultancy: Roche; Advisory / Consultancy: Merck Sharp & Dohme. P. Maroto: Advisory / Consultancy: Pfizer; Advisory / Consultancy: Novartis; Advisory / Consultancy: Janssen; Advisory / Consultancy, Research grant / Funding (institution): Roche; Advisory / Consultancy: Sanofi; Advisory / Consultancy: Bayer; Advisory / Consultancy: Bristol-Myers Squibb. S.F. Oosting: Research grant / Funding (institution): Celldex; Research grant / Funding (institution): Novartis. S. Fear: Full / Part-time employment: F. Hoffmann-La Roche. F. Di Nucci: Shareholder / Stockholder / Stock options, Full / Part-time employment: Roche/ Genentech. S. De Ducla: Shareholder / Stockholder / Stock options, Full / Part-time employment: F. Hoffmann-La Roche. E. Choy: Honoraria (self): AbbVie; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Lilly; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution): Novartis; Honoraria (self): ObsEva; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution): Pfizer; Honoraria (self): Merck Serono; Honoraria (self), Speaker Bureau / Expert testimony: Regeneron; Honoraria (self), Advisory / Consultancy: Roche/Genentech; Honoraria (self): R-Pharm; Honoraria (self): SynAct Pharma; Honoraria (self), Speaker Bureau / Expert testimony, Research grant / Funding (institution): Sanofi; Advisory / Consultancy: Sanofi/Regeneron; Speaker Bureau / Expert testimony: Bristol-Myers Squibb; Speaker Bureau / Expert testimony: Janssen; Speaker Bureau / Expert testimony, Research grant / Funding (institution): Roche; Speaker Bureau / Expert testimony: UCB; Research grant / Funding (institution): Bio-Cancer Treatment International; Research grant / Funding (institution): Biogen. All other authors have declared no conflicts of interest.
Resources from the same session
2664 - Phase (Ph) II study of MBG453 + spartalizumab in patients (pts) with non-small cell lung cancer (NSCLC) and melanoma pretreated with anti–PD-1/L1 therapy
Presenter: Nicholas Mach
Session: Poster Display session 3
Resources:
Abstract
1285 - Preliminary results of STELLAR-001, a dose escalation phase I study of the anti-C5aR, IPH5401, in combination with durvalumab in advanced solid tumors.
Presenter: Christophe Massard
Session: Poster Display session 3
Resources:
Abstract
3808 - GOLFIG chemo-immunotherapy in metastatic colorectal cancer (mCRC) patients: A fifteen year retrospective analysis
Presenter: Pierpaolo Correale
Session: Poster Display session 3
Resources:
Abstract
5677 - Immune correlates in peripheral blood samples in a preoperative window of opportunity randomized trial of nivolumab with or without tadalafil in resectable squamous cell carcinoma of the head and neck (SCCHN)
Presenter: Larry Harshyne
Session: Poster Display session 3
Resources:
Abstract
4854 - Phase 1 evaluation of AB928, a novel dual adenosine receptor antagonist, combined with chemotherapy or AB122 (anti-PD-1) in patients (pts) with advanced malignancies
Presenter: John Powderly
Session: Poster Display session 3
Resources:
Abstract
4344 - Phase 1 Trial of CV301 in Combination with Anti-PD-1 Therapy in Non-squamous NSCLC
Presenter: Arun Rajan
Session: Poster Display session 3
Resources:
Abstract
4555 - Safety and efficacy results of the combination of DPX-Survivac, pembrolizumab and intermittent low dose cyclophosphamide (CPA) in subjects with advanced and metastatic solid tumors: preliminary results from the hepatocellular carcinoma (HCC), NSCLC, bladder cancer, & MSI-H cohorts
Presenter: Henry Conter
Session: Poster Display session 3
Resources:
Abstract
3012 - Excellent CBR and Prolonged PFS in Non-Squamous NSCLC with Oral CA-170, an Inhibitor of VISTA and PD-L1
Presenter: Vivek Radhakrishnan
Session: Poster Display session 3
Resources:
Abstract
2536 - Phase Ib/II trial of TG4001 (Tipapkinogene sovacivec), a therapeutic HPV-vaccine, and Avelumab in patients with recurrent/metastatic (R/M) HPV-16+ cancers
Presenter: Christophe Le Tourneau
Session: Poster Display session 3
Resources:
Abstract
1845 - Induction of tumor-infiltrating functional CD8 positive cells and PD-L1 expression in esophageal cancer by S-588410
Presenter: Takashi Kojima
Session: Poster Display session 3
Resources:
Abstract