1A). 27% (19C37%). The median PFS (95% CI) from the start of second collection was 8.7 (5.6C13.7) mo. The median event follow-up duration was 19.4 (12.9C21.9) mo among the 25 individuals Ganetespib (STA-9090) without a PFS event. Eighty-six (83%) individuals experienced treatment-related adverse events; 31 of 103 (30%) experienced grade 3/4 events. Limitations were the small sample size and selection for progressors. Conclusions: The atezolizumab + bevacizumab combination experienced activity and was tolerable in individuals with progression on atezolizumab or sunitinib. Further studies are needed to investigate sequencing strategies in mRCC. Patient summary: Individuals with advanced kidney malignancy whose disease experienced worsened during treatment with atezolizumab or sunitinib began second-line treatment with atezolizumab + bevacizumab. Tumors shrank in more than one-quarter of individuals treated Ganetespib (STA-9090) with this combination, and side effects were workable. = 103)= 44)= 59)(%)83 (81)35 (80)48 (81)KPS 80, (%)98 (97) a41 (98)57 (97)Predominant obvious cell histology, (%)96 (93)40 (91)56 (95)Sarcomatoid component, (%)11 (11)5 (11)6 (10)MSKCC risk category, (%)?Beneficial (0)22 (21)12 (27)10 (17)?Intermediate (1 or 2 2)78 (76)30 (68)48 (81)?Poor (3)3 (3)2 (5)1 (2)1% of IC expressing PD-L1, (%) b63 (61)26 (59)37 (63)Geographic region, (%)?USA86 (83)44 (100)42 (71)?Western Union17 (17)0 c17 (29) Open in a separate windows IC = tumor-infiltrating immune cell; IQR = interquartile range; KPS = Karnofsky overall performance status; MSKCC = Memorial Sloan Kettering Malignancy Center; PD-L1 = programmed death-ligand 1. Clinical cutoff day: April 19, 2017. a= 101. bDenominators include individuals who were not evaluable. cAdvancing to second-line atezolizumab + bevacizumab from atezolizumab monotherapy was not Ganetespib (STA-9090) allowed in Western centers. 3.2. Effectiveness In 100 of 103 individuals evaluable for response (44 from your atezolizumab arm and 56 from your sunitinib arm), the ORR was 27% (27/100; 95% CI, 19C37%). The ORRs were 25% (11/44; 95% CI, 13C40%) in individuals who previously received atezolizumab and 29% (16/56; 95% CI, 17C42%) in individuals who previously received sunitinib (Table Ganetespib (STA-9090) 2). The ORR in individuals who responded to first-line treatment was 44% (7/16; 95% CI, 20C 70%), and it was 24% (20/84; 95% CI, 15C34%) in nonresponders (Table 2). Reactions to atezolizumab + bevacizumab occurred in nonresponders to both prior atezolizumab (= 9; 23% Ganetespib (STA-9090) [95% CI, 11C39%]) and sunitinib (= 11; 25% [95% CI, 13C 40%]). Forty individuals experienced either progressive disease (PD; = 21) or stable disease (SD; = 19) as the best response to first-line atezolizumab, and consequently four individuals (19%) with initial PD on atezolizumab accomplished a partial response (PR) on atezolizumab + bevacizumab. In individuals with PD-L1Cpositive tumors at baseline, the response rate to second-line atezolizumab + bevacizumab was 28% (95% CI, 17C41%; Table 2); it was 22% (95% CI, 10C38%) in individuals with PD-L1Cnegative tumors (Supplementary Table 2). Table 2C Confirmed investigator-assessed reactions (RECIST 1.1) in individuals who advanced to second-line atezolizumab + bevacizumab = 100)(%) [95% CI]27 (27) [19C37]?CR (%)1?PR (%)26?SD (%)37?PD (%)32= 44)After sunitinib a (= 56) (%) [95% CI]11 (25) [13C40]16 (29) [17C42] = 16)Nonresponder = 84) (%) [95% CI]7 (44) [20C70]20 (24) [15C34] = 60)(%) [95% CI]17 (28) [17C41] Open in a separate windows CI = confidence interval; CR = total response; ORR = objective response rate; PD = progressive disease; PD-L1 = programmed death-ligand 1; PR = partial response; RECIST = Response Evaluation Criteria in Solid Tumors; SD = stable disease. aThree individuals in the postsunitinib arm without postbaseline tumor assessment were not included in the analysis. bOne patient in the postatezolizumab arm experienced non-CR/non-PD as the best overall response. cBased on archival cells and/or biopsy. No obvious pattern in response could be identified based on Memorial Sloan Kettering Malignancy Rabbit polyclonal to ANKRD40 Center risk score. For individuals with beneficial (= 22), intermediate (= 75), and poor (= 3) risk, ORRs were 18% (95% CI, 5C40%; = 4), 31% (95% CI, 21C42%; = 23), and 0% (95% CI, 0C71%), respectively. For individuals whose tumors experienced a sarcomatoid component (= 11), ORR was 9% (95% CI, 0C41%; = 1), and for those.
1A)