The Phase 3 IMmotion151 trial demonstrated that the combination of atezolizumab (atezo) and bevacizumab (bev) demonstrated an improved progression-free survival (PFS) compared to sunitinib (sun) alone in untreated mRCC pts, 362 (40%) of 915 patients had PD-L1 positive disease. In that study, they found that in the PD-L1 positive population, the median progression-free survival was 11.2 months in the atezolizumab plus bevacizumab group versus 7.7 months in the sunitinib group (hazard ratio [HR] 0·74 [95% CI 0·57-0·96]; p=0·0217). In the ITT population, the median overall survival had an HR of 0.93 (0·76-1·14) and the results did not cross the significance boundary at the interim analysis. The results are summarized below:
In this poster, the authors focus on patient-reported outcomes specifically, offering an opportunity to evaluate PROs with immunotherapy and VEGF-directed therapy alone and in combination.
The full study protocol is seen below:
As a reminder, in the original study, patients were randomized to receive atezolizumab 1200 mg IV q3w and bevacizumab 15 mg/kg IV q3w or sunitinib 50 mg po qd for 4w on, 2w off. Coprimary endpoints were reported previously, as indicated above. Secondary endpoints included PROs. All participants completed the MD Anderson Symptom Inventory (MDASI) and Brief Fatigue Inventory (BFI) every 3 weeks of each 6-wk cycle until progression (RECIST 1.1). Time to deterioration (TTD; first ≥ 2-point score increase over baseline [BL]) and change from BL (effect size [ES] ≥ 0.2 suggests a clinically important difference vs sunitinib) in MDASI symptom severity and interference and BFI fatigue severity and interference scores are reported for all-comers. The tools used from PRO are summarized below:
Completion rates were > 90% at BL and ≥ 80% at most visits across arms, generating good response rates. Baseline PRO scores indicating mild symptoms and interference were similar across arms, as seen below:
In general, this demonstrates that these patients are relatively asymptomatic at baseline.
Delayed TTD of symptom severity and interference with daily life was seen with atezo vs sunitinib and atezo + bev vs sunitinib and was longest with atezo alone; the full results are seen below:
The KM curves were presented on the abstract. It should be noted that atezo/bev was almost similar to placebo, whereas patients with atezo monotherapy did the best.
Patients reported milder symptoms and less interference during the first 6 cycles with atezo vs sunitinib: ES mean (range) was 0.36 (0.07-0.68) for core symptom severity and 0.36 (0.04-0.83) for symptom interference. The five worst patient-reported symptoms during treatment were dry mouth, fatigue, rash, drowsiness, lack of appetite – and all were in the sunitinib arm. All 16 symptoms measured were milder with atezolizumab than with sunitinib – seen below:
Based on these PROs, the study results suggest that atezolizumab alone or with bevacizumab maintained patients’ daily function with minimal symptom interference as compared to sunitinib.
Clinical trial information: NCT01984242
Presented by: Sumanta K. Pal, MD, Co-director, Kidney Cancer Program, Medical Oncologist, City of Hope
Co-authors: David F. McDermott, Michael B. Atkins, Bernard Escudier, Brian I. Rini, Robert J. Motzer, Lawrence Fong, Richard Wayne Joseph, Stephane Oudard, Alain Ravaud, Sergio Bracarda, Cristina Suarez Rodriguez, Elaine Tat Lam, Toni K. Choueiri, Beiying Ding, Caroleen Quach, Kenji Hashimoto, Christina Schiff, Elisabeth Piault, Thomas Powles
Written by: Thenappan Chandrasekar, MD, Clinical Instructor, Thomas Jefferson University, @tchandra_uromd, @JEFFUrology, at the 2019 ASCO Annual Meeting #ASCO19, May 31- June 4, 2019, Chicago, IL USA
- Rini et al. “Atezolizumab plus bevacizumab versus sunitinib in patients with previously untreated metastatic renal cell carcinoma (IMmotion151): a multicentre, open-label, phase 3, randomised controlled trial.” Lancet. 2019 May 9. pii: S0140-6736(19)30723-8. doi: 10.1016/S0140-6736(19)30723-8. [Epub ahead of print]