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301 Association of response with survival outcomes with atezolizumab in combination with vemurafenib and cobimetinib in the phase 3 IMspire150 study
  1. Paolo Ascierto,
  2. Karl Lewis2,
  3. Caroline Robert3,
  4. Daniil Stroyakovskiy4,
  5. Helen Gogas5,
  6. Svetlana Protsenko6,
  7. Rodrigo Pereira7,
  8. Thomas Eigentler8,
  9. Piotr Rutkowski9,
  10. Lev Demidov10,
  11. Georgy Moiseevich Manikhas11,
  12. Haocheng Li12,
  13. Qian Zhu13,
  14. Edward McKenna13,
  15. Virginia McNally14,
  16. Ralf Gutzmer15 and
  17. Grant McArthur16
  1. 1Istituto Nazionale Tumori IRCCS Fondazio, Napoli, Italy
  2. 2University of Colorado Comprehensive CC, Aurora, CO, USA
  3. 3Gustave Roussy and Université Paris, Villejuif-Paris, France
  4. 4Moscow City Oncology Hospital #62, Istra, Russian Federation
  5. 5Laiko General Hospital, Athens, Greece
  6. 6N. N. Petrov Nat’l Medical Research Ctr of Oncology, St. Petersburg, Russian Federation
  7. 7Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil
  8. 8University Hospital Tübingen, Tübingen, Germany
  9. 9Maria Sklodowska-Curie National Research, Warsaw, Poland
  10. 10N. N. Blokhin Russian Cancer Research, Moscow, Russian Federation
  11. 11St. Petersburg Oncology Hospital, St. Petersburg, Russian Federation
  12. 12F. Hoffmann–La Roche Ltd, Mississauga, Canada
  13. 13Genentech, Inc., South San Francisco, CA, USA
  14. 14Roche Products Ltd., Welwyn Garden City, UK
  15. 15Haut-Tumour-Zentrum Hannover (HTZH), Hannover, Germany
  16. 16Peter MacCallum Cancer Centre, Melbourne, Australia


Background The phase 3 IMspire150 study (NCT02908672) demonstrated improved progression-free survival (PFS) with first-line atezolizumab (A) vs placebo (P) combined with vemurafenib (V) + cobimetinib (C) in patients with BRAFV600 mutation–positive advanced melanoma (15.1 vs 10.6 months; hazard ratio [HR] 0.78; 95% confidence interval [CI] 0.63–0.97; P=0.0249). Objective response has been associated with increased survival with chemotherapy and targeted therapies, but it is unclear whether the association holds for immunotherapy. In this exploratory analysis, we evaluated the impact of response on survival outcomes in patients treated with A+V+C or P+V+C in the IMspire150 study.

Methods 514 patients were randomized 1:1 to A+V+C (n=256) or P+V+C (n=258). Patients received V+C in cycle 1; A or P was added on days 1+15 from cycle 2 onward. The primary endpoints for this exploratory analysis were PFS and overall survival (OS), estimated using the Kaplan-Meier method. Outcomes were analyzed by investigator-assessed best overall response (BOR) per RECIST v1.1 (complete response [CR] vs partial response [PR] vs stable disease [SD]).

Results Median follow-up was 18.9 mo. In the A+V+C arm, BOR was CR (n=41), PR (n=129), and SD (n=58); in the P+V+C arm, BOR was CR (n=46), PR (n=122), and SD (n=58). An imbalance in baseline prognostic factors (eg, lactate dehydrogenase, tumor burden measures) was noted across response categories in both treatment arms, with favorable factors more prevalent in patients with CR and unfavorable factors more prevalent in patients with PR/SD. Improvement in PFS and OS was observed with A+V+C vs P+V+C in patients with PR, with 2-year PFS rates of 42.1% vs 24.6% and 2-year OS rates of 69.1% vs 56.1% with A+V+C vs P+V+C (table 1). In patients with CR, median PFS and OS were not yet reached in either arm, with 2-year PFS rates of 64.6% vs 59.8% and 2-year OS rates of 82.6% vs 82.8% with A+V+C vs P+V+C. PFS and OS outcomes were poor in both treatment arms in patients with SD, with 2-year PFS rates of 10.7% vs not estimable (NE) and 2-year OS rates of 36.6% vs 29.3% with A+V+C vs P+V+C.

Abstract 301 Table 1

PFS and OS outcomes with A+V+C vs P+V+C by BOR per RECIST v1.1

Conclusions PFS and OS improvement was observed for A+V+C vs P+V+C for patients who achieved PR. CR is associated with improved PFS and OS with both A+V+C and P+V+C. Further follow-up is required to determine the impact of A+C+V vs P+C+V on survival outcomes.

Trial Registration ClinicalTrials. gov, NCT02908672

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