Adding immunotherapy to chemotherapy prolongs progression free survival in bladder cancer [ESMO 2019 Press Release]

30 Sep 2019
Genitourinary cancers

BARCELONA, Spain - Patients with metastatic urothelial cancer have longer progression free survival when treated with first-line immunotherapy and chemotherapy instead of chemotherapy alone, according to late breaking results of the IMvigor130 trial presented at the ESMO Congress 2019 in Barcelona, Spain. (1)

Urothelial cancer, of which around 90% arises from the bladder, is the fifth most common cancer in Europe. Cisplatin based chemotherapy has been the standard first-line treatment for metastatic disease since the 1980s but up to half of patients are not fit enough to receive it, while those treated survive about 15 months on average. Immunotherapies such as the PD-L1 inhibitors atezolizumab and pembrolizumab are approved for patients ineligible or unresponsive to chemotherapy. IMvigor130 is the first trial to test the combination of chemotherapy and immunotherapy in patients eligible and ineligible for chemotherapy.

Compared to chemotherapy alone, chemotherapy plus atezolizumab improved the median time to progression of metastatic tumours by two months. Patients receiving the combination had an 18% reduced likelihood of progression. Interim analysis of overall survival showed a trend for improvement with the combination, but it was not statistically significant. There was also a trend for improved survival in patients with overexpression of PD-L1 who were treated with atezolizumab alone compared to chemotherapy.

grande-enrique

Study author Dr Enrique Grande, MD Anderson Cancer Centre Madrid, Spain, said the side-effects from combined chemotherapy and immunotherapy were consistent with studies in other solid tumours. “This is a new option for the upfront treatment of patients with metastatic urothelial cancer. Longer follow-up is needed on overall survival and we will continue to search for biomarkers to identify which patients respond best to this therapy.”

Commenting on the results for ESMO, Dr Ignacio Durán, Hospital Universitario Marques de Valdecilla-IDIVAL, Santander, Spain, cautioned that this improvement in progression free survival may be insufficient for regulatory approval at this stage, but said the data look promising.

Durán noted that the so-called “complete responses” – understood as relevant shrinkage or disappearance of cancer metastases – were around twice as likely with the combination compared to chemotherapy or immunotherapy alone. “This is remarkable. We are now eager to see if patients receiving the two therapies together live longer, and with a similar quality of life, than those receiving chemotherapy and immunotherapy alone or sequentially. The interim analysis of overall survival seems to be promising, but data are immature: overall survival data are needed to consider the combination of chemotherapy and immunotherapy as a new standard of care,” he said.

Study results

IMvigor130 (NCT02807636) randomly allocated 1,213 patients with metastatic urothelial cancer from 35 countries in a 1:1:1 ratio to atezolizumab plus platinum-based chemotherapy (Arm A), atezolizumab alone (Arm B), or placebo plus platinum-based chemotherapy (Arm C).

The coprimary efficacy endpoints were investigator-assessed progression free survival and overall survival (Arm A versus C) and overall survival (Arm B versus C). After a median follow-up of 11.8 months, median progression free survival was 8.2 months in Arm A and 6.3 months in Arm C. This corresponded to a statistically significant hazard ratio (HR) of 0.82 (95% confidence interval [CI] 0.70–0.96; P = 0.007).

In an interim analysis, median overall survival was 16.0 versus 13.4 months in Arms A and C, respectively (HR 0.83; 95% CI 0.69–1.00; P = 0.027) and 15.7 versus 13.1 months in Arms B and C, respectively (HR 1.02; 95% CI 0.83–1.24).

Objective response rates were 47%, 23% and 44% in Arms A, B and C, respectively. Complete response rates were 13%, 6% and 7% in Arms A, B and C, respectively. Adverse events leading to treatment withdrawal occurred in 34%, 6% and 34% of patients in Arms A, B and C, respectively. 

Official Congress Hashtag: #ESMO19
Social Media information

 

References

  1. LBA14_PR ‘IMvigor130: Efficacy and safety from a Phase 3 study of atezolizumab (atezo) as monotherapy or combined with platinum-based chemotherapy (PBC) vs placebo + PBC in previously untreated locally advanced or metastatic urothelial carcinoma (mUC)‘ will be presented by Enrique Grande during the Presidential Symposium III on Monday, 30 September, 16:30 to 18:15 (CEST) in the Barcelona Auditorium (Hall 2). Annals of Oncology, Volume 30, Supplement 5, October 2019 

LBA14_PR - IMvigor130: efficacy and safety from a Phase III study of atezolizumab (atezo) as monotherapy or in combination with platinum-based chemotherapy (PBC) vs placebo + PBC in previously untreated locally advanced or metastatic urothelial carcinoma (mUC)

E. Grande1, M. Galsky2, J.A. Arranz Arija3, M. De Santis4, I.D. Davis5, U.F.F. De Giorgi6, M. Mencinger7, E. Kikuchi8, X. Garcia del Muro9, M. Gumus10, M. Özgüroğlu11, A. Rezazadeh Kalebasty12, S.H. Park13, B.Y. Alekseev14, F.A.B. Schutz15, J.-R. Li16, A. Mecke17, S. Mariathasan18, A. Thastrom19, A. Bamias20
1Head Of Medical Oncology Department, MD Anderson Cancer Center Madrid, Madrid,Spain, 2Tisch Cancer Institute, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York,United States of America, 3Oncology, Hospital General Universitario Gregorio Marañon, Madrid, Spain, 4Urology, Charité University Hospital, Berlin/Germany, 5Eastern Health Clinical School, Monash University, Melbourne,Australia, 6Medical Oncology Department, Istituto Tumori della Romagna I.R.S.T., Meldola, Italy, 7Medical Oncology Department, Institute of Oncology, Ljubljana/Slovenia, 8Department Of Urology, Keio University, Tokyo, Japan, 9Medical Oncology, ICO - Institut Catala d'Oncologia Hospital Duran i Reynals, Hospitalet de Llobregat, Spain, 10Medical Oncology, Istanbul Medeniyet University, Goztepe Research Hospital, Istanbul, Turkey, 11Istanbul University-cerrahpaşa, Cerrahpaşa School of Medicine, Istanbul, Turkey, 12Medical Oncology, Norton Cancer Institute, Louisville, United States of America, 13Division Of Hematologyoncology, Department Of Medicine, Samsung Medical Center, Seoul, Korea, Republic of, 14Oncourology, P. A. Herzen Moscow Oncology Research Institute, Ministry of Health of the Russian Federation, Moscow, Russian Federation, 15Medical Oncology, Beneficencia Portuguesa de Sao Paulo, Sao Paulo, Brazil, 16Division Of Urology/department Of Surgery, Taichung Veterans General Hospital/HungKuang University, Taichung, Taiwan, 17Product Development Oncology, F. Hoffmann-La Roche Ltd, Basel, Switzerland, 18Oncology Biomarker Department, Genentech, Inc., South San Francisco, United States of America, 19Product Development Oncology, Genentech, Inc., South San Francisco, United States of America, 20National and Kapodistrian University of Athens, Athens, Greece

Background: First-line (1L) mUC treatment (tx) includes cisplatin (cis)- or carboplatin (carbo)-based chemotherapy or checkpoint inhibitors, depending on patient (pt) eligibility and PD-L1 status. IMvigor130 is a Phase 3, global, multicentre, randomised, partially blinded study evaluating atezo (anti–PD-L1) alone or with PBC vs placebo + PBC in untreated mUC.
Methods: IMvigor130 enrolled 1213 PBC-eligible pts with mUC. Pts were randomised 1:1:1 to Arm A (atezo + PBC [gemcitabine (gem) + either cis or carbo]), Arm B (atezo) or Arm C (placebo + PBC). Gem 1000 mg/m2 IV was given on Day (D) 1 and D8, carbo AUC 4.5 IV or cis 70 mg/m2 IV on D1 and atezo/placebo or atezo 1200 mg IV on D1 of each 3-wk tx cycle. Tumours were assessed at baseline and every 9 wk until (INV)-assessed PD per RECIST 1.1 or other events. Coprimary efficacy endpoints are INV-assessed PFS and OS (Arm A vs C) and OS (Arm B vs C, hierarchical approach) per RECIST 1.1. Final PFS (Arm A vs C) and interim OS are shown here.
Results: With a median follow-up of 11.8 mo, median PFS was 8.2 mo in Arm A vs 6.3 mo in Arm C (HR, 0.82 [95% CI: 0.70, 0.96]; P = 0.007). The comparison of OS did not cross the prespecified interim efficacy boundary, with a median of 16.0 mo in Arm A and 13.4 mo in Arm C (HR, 0.83 [95% CI: 0.69, 1.00]; P = 0.027; Table). For Arm B vs C, the median OS was 15.7 and 13.1 mo, respectively (HR, 1.02 [95% CI: 0.83, 1.24]), for ITT pts and not estimable and 17.8 mo, respectively (HR, 0.68 [95% CI: 0.43, 1.08]), for PD-L1 IC2/3 pts. ORRs were 47%, 23% and 44% and CR rates were 13%, 6% and 7% for Arms A, B and C, respectively. AEs that led to tx withdrawal occurred in 34%, 6% and 34% of pts in Arms A, B and C, respectively.
Conclusions: Adding atezo to PBC for 1L mUC tx prolonged PFS vs PBC alone in pts with untreated mUC. The combination safety profile was consistent with that observed for the individual agents.

ESMO-2019-Press-Release-Grande

Clinical trial identification: NCT02807636
Editorial acknowledgement: Medical writing assistance for this abstract was provided by Paige Davies, PhD, of Health Interactions, and funded by F. Hoffmann-La Roche, Ltd.
Legal entity responsible for the study: F. Hoffmann-La Roche, Ltd.
Funding: F. Hoffmann-La Roche, Ltd.
Disclosure: E. Grande: Speaker Bureau / Expert testimony, Research grant / Funding (self): Pfizer; Speaker Bureau / Expert testimony, Research grant / Funding (self): Ipsen; Speaker Bureau / Expert testimony: BMS; Speaker Bureau / Expert testimony: Eisai; Speaker Bureau / Expert testimony, Research grant / Funding (institution): Roche; Speaker Bureau / Expert testimony, Research grant / Funding (institution): MSD; Speaker Bureau / Expert testimony: Sanofi-Genzyme; Speaker Bureau / Expert testimony: Adacap; Speaker Bureau / Expert testimony: Novartis; Speaker Bureau / Expert testimony: EUSA Pharma; Speaker Bureau / Expert testimony: Pierre Fabre; Speaker Bureau / Expert testimony, Research grant / Funding (self): Lexicon; Speaker Bureau / Expert testimony: Celgene; Research grant / Funding (self): AstraZeneca; Research grant / Funding (self): MTEM/Threshold; Advisory / Consultancy: ENETS; Officer / Board of Directors: GETNE; Officer / Board of Directors: GETHI.
M. Galsky: Advisory / Consultancy, Research grant / Funding (institution): Janssen; Advisory / Consultancy, Research grant / Funding (institution): Dendreon; Advisory / Consultancy, Research grant / Funding (institution): Merck; Advisory / Consultancy, Research grant / Funding (institution): Genentech; Advisory / Consultancy, Research grant / Funding (institution): Bristol Myers Squibb; Advisory / Consultancy, Research grant / Funding (institution): AstraZeneca; Advisory / Consultancy: BioMotiv; Advisory / Consultancy: Glaxo Smith Kline; Advisory / Consultancy: Lilly; Advisory / Consultancy: Astellas; Advisory / Consultancy: Novartis; Advisory / Consultancy: Pfizer; Advisory / Consultancy: EMD-Serono; Advisory / Consultancy: Seattle Genetics; Advisory / Consultancy: Incyte; Advisory / Consultancy: Aileron; Advisory / Consultancy: Dracen; Advisory / Consultancy: Inovio; Advisory / Consultancy: Dragonfly.
J.A. Arranz Arija: Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: BMS; Research grant / Funding (institution): Novartis; Research grant / Funding (institution): Pierre Fabre Oncology; Advisory / Consultancy: Astellas; Honoraria (self), Advisory / Consultancy: Ipsen; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Janssen; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: MSD; Advisory / Consultancy: Merck; Advisory / Consultancy, Travel / Accommodation / Expenses: Pfizer; Honoraria (self): Roche; Honoraria (self): Cilag; Travel / Accommodation / Expenses: ESSA; Travel / Accommodation / Expenses: Ferring.
M. De Santis: Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Amgen, Astellas, AstraZeneca, Bayer, Bioclin; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: BMS, EISAI, Roche; Honoraria (self), Travel / Accommodation / Expenses: Clovis, Incyte; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: ESSA; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Ferring; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Ipsen; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Janssen; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: MSD; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Merck; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Novartis; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: OncoGenex; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Pfizer; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Pierre Fabre Oncology; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Sandoz; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Sanofi; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: SeaGen; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Shionogi, Synthon, Takeda; Non-remunerated activity/ies: EAU Prostrate Cancer Guidelines; Non-remunerated activity/ies: ESMO Bladder Cancer Practice Guidelines; Non-remunerated activity/ies: S3 Blasenkarzinom Leitlinien.
I.D. Davis: Honoraria (institution), Advisory / Consultancy: Amrad; Honoraria (institution), Advisory / Consultancy: Sanofi (and Sanofi-aventis); Honoraria (institution), Advisory / Consultancy: NovoNordisk; Honoraria (institution), Advisory / Consultancy: Bayer; Honoraria (institution), Advisory / Consultancy: Pharmion ; Honoraria (institution), Advisory / Consultancy: Wyeth; Honoraria (institution), Advisory / Consultancy: Schering-Plough; Honoraria (institution), Advisory / Consultancy: Novartis; Honoraria (institution), Advisory / Consultancy: GSK; Honoraria (institution), Advisory / Consultancy: Medivation; Honoraria (institution), Advisory / Consultancy: Janssen; Honoraria (institution), Advisory / Consultancy: Dendreon; Honoraria (institution), Advisory / Consultancy: Ipsen; Honoraria (institution), Advisory / Consultancy: Astellas; Honoraria (institution), Advisory / Consultancy: Roche; Honoraria (institution), Advisory / Consultancy: Eisai; Honoraria (institution), Advisory / Consultancy: Pfizer; Honoraria (institution), Advisory / Consultancy: BMS, AstraZeneca; Research grant / Funding (institution): NHMRC Practitioner Fellowship; Officer / Board of Directors: ANZUP.
U.F.F. De Giorgi: Research grant / Funding (institution): AstraZeneca; Research grant / Funding (institution): Roche; Advisory / Consultancy, Research grant / Funding (institution): Sanofi; Advisory / Consultancy: Astellas; Advisory / Consultancy: Bayer; Advisory / Consultancy, Travel / Accommodation / Expenses: BMS; Advisory / Consultancy, Travel / Accommodation / Expenses: Ipsen; Advisory / Consultancy, Travel / Accommodation / Expenses: Janssen; Advisory / Consultancy: Merck; Advisory / Consultancy, Travel / Accommodation / Expenses: Pfizer.
M. Mencinger: Advisory / Consultancy: Sanofi; Speaker Bureau / Expert testimony: BMS; Advisory / Consultancy: Merck; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Pfizer; Honoraria (self), Speaker Bureau / Expert testimony: Bayer; Honoraria (self), Speaker Bureau / Expert testimony: roche; Honoraria (self), Speaker Bureau / Expert testimony: Janssen; Honoraria (self), Speaker Bureau / Expert testimony: Astellas.
E. Kikuchi: Honoraria (self), Research grant / Funding (institution): MSD; Honoraria (self), Research grant / Funding (institution): NIPPON; Research grant / Funding (institution): KAYAKU; Honoraria (self), Research grant / Funding (institution): Astellas; Honoraria (self), Research grant / Funding (institution): ONO; Honoraria (self), Research grant / Funding (institution): Chugai; Honoraria (self), Research grant / Funding (institution): Takeda; Honoraria (self), Research grant / Funding (institution): Taiho; Honoraria (self), Research grant / Funding (institution): AstraZeneca; Honoraria (self): KISSEI; Honoraria (self): ASKA; Honoraria (self): SHINYAKU; Honoraria (self): Pfizer.
X. Garcia del Muro: Research grant / Funding (institution): AstraZeneca; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Pfizer; Advisory / Consultancy, Travel / Accommodation / Expenses: BMS; Advisory / Consultancy, Travel / Accommodation / Expenses: Ipsen; Advisory / Consultancy, Travel / Accommodation / Expenses: Roche; Honoraria (self), Advisory / Consultancy: Lilly; Advisory / Consultancy: Pharmamar; Advisory / Consultancy: Eusapharma; Honoraria (self), As a speaker or moderator in Scientific Meeting: Astellas.
M. Gumus: Honoraria (self), Advisory / Consultancy: Lilly; Honoraria (self), Advisory / Consultancy: MSD; Honoraria (institution), Advisory / Consultancy, Travel / Accommodation / Expenses: Pfizer; Honoraria (self), Advisory / Consultancy: Astellas; Honoraria (self), Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Amgen.
M. Özgüroğlu: Honoraria (self), Honoraria (institution), Advisory / Consultancy, Travel / Accommodation / Expenses: Janssen; Honoraria (self), Honoraria (institution), Advisory / Consultancy: Sanofi; Honoraria (self), Honoraria (institution), Advisory / Consultancy: Astellas; Honoraria (self), Honoraria (institution): Novartis; Honoraria (self), Honoraria (institution): Roche; Travel / Accommodation / Expenses: BMS.
A. Rezazadeh Kalebasty: Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution), Travel / Accommodation / Expenses: Genentech, Inc./Roche; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution), Travel / Accommodation / Expenses: Exelixis; Honoraria (self), Speaker Bureau / Expert testimony, Research grant / Funding (institution), Travel / Accommodation / Expenses: Janssen; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution), Travel / Accommodation / Expenses: AstraZeneca; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Bayer; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution): BMS; Honoraria (self), Speaker Bureau / Expert testimony, Research grant / Funding (institution), Travel / Accommodation / Expenses: Eisai; Research grant / Funding (institution): Macrogenics; Honoraria (self), Speaker Bureau / Expert testimony, Research grant / Funding (institution), Travel / Accommodation / Expenses: Astellas; Research grant / Funding (institution): beyond spring; Research grant / Funding (institution): Bioclin; Research grant / Funding (institution): Clovis; Research grant / Funding (institution): Bavarian Nordic; Research grant / Funding (institution): Seattle Genetics; Honoraria (self), Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Pfizer; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Novartis; Honoraria (self), Speaker Bureau / Expert testimony: Amgen; Shareholder / Stockholder / Stock options: ECOM; Honoraria (self), Speaker Bureau / Expert testimony: Sanofi; Travel / Accommodation / Expenses: Prometheus Labs.
B.Y. Alekseev: Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self), Research grant / Funding (institution), Travel / Accommodation / Expenses: Astellas; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self), Research grant / Funding (institution), Travel / Accommodation / Expenses: AstraZeneca; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self), Research grant / Funding (institution), Travel / Accommodation / Expenses: Bayer; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self), Research grant / Funding (institution), Travel / Accommodation / Expenses: BMS; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self), Research grant / Funding (institution), Travel / Accommodation / Expenses: MSD; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self), Research grant / Funding (institution), Travel / Accommodation / Expenses: Pfizer; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self), Research grant / Funding (institution), Travel / Accommodation / Expenses: Sanofi; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self), Research grant / Funding (institution), Travel / Accommodation / Expenses: Roche; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self), Research grant / Funding (institution), Travel / Accommodation / Expenses: Janssen; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Ferring.
F.A.B. Schutz: Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: MSD; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Bayer; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: BMS; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Roche; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Janssen; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Astellas; Advisory / Consultancy, Spouse / Financial dependant: Ipsen.
A. Mecke: Travel / Accommodation / Expenses, Shareholder / Stockholder / Stock options, Full / Part-time employment: F. Hoffmann-La Roche.
S. Mariathasan: Shareholder / Stockholder / Stock options, Full / Part-time employment: Roche/GNE.
A. Thastrom: Shareholder / Stockholder / Stock options, Full / Part-time employment: Genentech, Inc..
A. Bamias: Honoraria (self), Research grant / Funding (institution): Roche; Honoraria (self), Research grant / Funding (institution): BMS; Honoraria (self), Research grant / Funding (institution): AstraZeneca.

Last update: 30 Sep 2019

This press release contains information provided by the author of the highlighted abstract and reflects the content of this abstract. It does not necessarily reflect the views or opinions of ESMO who cannot be held responsible for the accuracy of the data. Commentators quoted in the press release are required to comply with the ESMO Declaration of Interests policy and the ESMO Code of Conduct.

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