Treatment Beyond Progression in Patients with Advanced Renal Cell Carcinoma Treated with Nivolumab in CheckMate 025

Escudier, Bernard; Motzer, Robert J.; Sharma, Padmanee; Wagstaff, John; Plimack, Elizabeth R.; Hammers, Hans J.; Donskov, Frede; Gurney, Howard; Sosman, Jeffrey A.; Zalewski, Paweł; Harmenberg, Ulrika; McDermott, David F.; Choueiri, Toni K.; Richardet, Martin Eduardo; Tomita, Yoshihiko; Ravaud, Alain; Doan, Justin; Zhao, Huanyu; Hardy, Hélène; George, Saby

doi:10.1016/j.eururo.2017.03.037

Cited by 208 publications

(138 citation statements)

References 15 publications

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“…In the context of all patients randomized to receive nivolumab in the trial, this translates to an efficacy benefit of treatment beyond progression in 1.3% (3 of 240). 14,15 In CheckMate 141, the ORR before RECISTdefined progression was higher in the TBP group than It is important to note that although interesting, the small patient numbers in our study preclude us from drawing definitive conclusions about patient characteristics predictive of clinical benefit from treatment with nivolumab beyond RECIST-defined progression. 2 In a landmark analysis, the median OS starting week 6 after RECISTdefined progression was 8.4 months for the TBP group and 3.8 months for the NTBP group.…”

Section: Discussionmentioning

confidence: 62%

Nivolumab treatment beyond RECIST‐defined progression in recurrent or metastatic squamous cell carcinoma of the head and neck in CheckMate 141: A subgroup analysis of a randomized phase 3 clinical trial

Haddad

Concha-Benavente

Blumenschein

et al. 2019

Cancer

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Background Response patterns with immune checkpoint inhibitors may be different from those with chemotherapy. Therefore, assessment of response to immunotherapy with the Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1, could result in premature treatment termination. The randomized, open‐label, phase 3 CheckMate 141 trial (NCT02105636), which evaluated nivolumab in recurrent/metastatic squamous cell carcinoma of the head and neck after platinum therapy, allowed treatment beyond first RECIST‐defined progression (TBP) according to protocol‐specified criteria. Methods In CheckMate 141, patients with RECIST‐defined progression who had a stable performance status and demonstrated clinical benefit without rapid disease progression were permitted to receive TBP with nivolumab at 3 mg/kg every 2 weeks until further progression, which was defined as an additional ≥10% increase in tumor volume. This post hoc analysis evaluated outcomes for patients who received TBP with nivolumab. Results Of 240 patients randomized to nivolumab, 146 experienced RECIST‐defined progression. Sixty‐two of these patients received TBP, and 84 discontinued treatment (no TBP). Among the 60 TBP patients evaluable for response, 15 (25%) had no change in their tumor burden, and 15 (25%) had reductions in target lesion size; 3 patients (5%) had reductions >30%. The median overall survival among TBP patients was 12.7 months (95% confidence interval, 9.7‐14.6 months). No new safety signals were observed with TBP. Exploratory analyses of immune cell biomarkers suggested a potential relationship with initial and TBP responses. Conclusions Tumor burden reduction was noted in a proportion of patients who received TBP with nivolumab in CheckMate 141. Additional research is warranted to identify factors predictive of a TBP benefit in this population.

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Section: Discussionmentioning

confidence: 62%

Nivolumab treatment beyond RECIST‐defined progression in recurrent or metastatic squamous cell carcinoma of the head and neck in CheckMate 141: A subgroup analysis of a randomized phase 3 clinical trial

Haddad

Concha-Benavente

Blumenschein

et al. 2019

Cancer

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“…Although these systemic agents have been replaced by molecular, targeted therapies during the last years, the immunogenic potential of RCC remains an exciting avenue for future study. Immunotherapy with antibodies against the programmed cell death protein 1 (PD-1) or its ligand 1 (PD-L1) have demonstrated excellent preliminary results (48)(49)(50). Interestingly, SBRT might also be applied to enhance immunogenic the anti-tumor response via the abscopal effect: clinical studies have described regression of non-irradiated distant lesions following SBRT to an RCC metastasis (51)(52)(53).…”

Section: Toxicitymentioning

confidence: 99%

Stereotactic body radiotherapy (SBRT) for pulmonary metastases from renal cell carcinoma—a multicenter analysis of the German working group “Stereotactic Radiotherapy”

Hoerner-Rieber¹,

Duma²,

Blanck³

et al. 2017

J. Thorac. Dis.

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Background: Renal cell carcinoma (RCC) is traditionally considered to be radioresistant. Radiotherapy response rates are believed to improve with hypofractionated, high dose stereotactic body radiotherapy (SBRT).However, limited data exist regarding the role of SBRT in the treatment of pulmonary metastases. Methods: The working group "Stereotactic Radiotherapy" of the German Society of Radiation Oncology analyzed its multi-institutional database of more than 700 patients who received SBRT for pulmonary metastases. Treatment was performed at 10 centers between 2001 and 2016. Patients with metastatic RCC were included in the study. Tumor characteristics, treatment details, and follow-up data including survival, local control (LC), distant metastases, and toxicity were evaluated. Results: A total of 46 RCC patients treated with SBRT for 67 lung metastases were identified, who received a median total biologically effective dose (BED iso ) at planning target volume (PTV) isocenter of 117.0 Gy (range, 48.0-189.0 Gy). A median fractional dose of 20.8 Gy at isocenter (range, 6.0-37.9 Gy) was administered in a median number of 3 fractions (1-8 fractions). After a median follow-up time of 28.3 months for all patients, 1-and 3-year LC rates were 98.1% and 91.9%, with corresponding 1-and 3-year overall survival (OS) of 84.3% and 43.8%, respectively. Pulmonary metastases treated with BEDiso ≥130 Gy showed a trend for superior LC (P=0.054). OS was significantly improved in both uni-and multivariate analysis for patients with higher Karnofsky performance scale, lower maximum pulmonary metastasis diameter and lack of post-SBRT systemic therapy due to progression (P=0.014; P=0.049; P=0.006). Only mild acute and late toxicity was reported.

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“…For example, in various Checkmate trials, the criteria to treat beyond progression was tolerability and apparent clinical benefit, assessed at the discretion of the investigator [14, 15]. The presumption is that only those with favorable clinical characteristics at progression would merit continuing the same treatment instead of changing to another.…”

Section: Discussionmentioning

confidence: 99%

Pushing the limits of immune-related response: a case of “extreme pseudoprogression”

Wong

Thian

Kapur

et al. 2018

Cancer Immunol Immunother

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The advent of immune checkpoint targeted immunotherapy has seen a spectrum of immune-related phenomena in both tumor responses and toxicities. We describe a case of pseudoprogression that pushes the limits of immune-related response criteria and challenges the boundaries and definitions set by trial protocols. A middle-aged man with conventional clear cell renal cell carcinoma (RCC) had received multiple prior systemic treatments including vascular endothelial growth factor receptor tyrosine kinase inhibitors, as well as multiple surgeries and radiotherapy treatments. He was eventually started on nivolumab—the anti-programmed death receptor-1 monoclonal antibody approved for the treatment of advanced RCC. Clinical deterioration was observed soon after a 100 mg dose of nivolumab, with onset of acute renal failure and declining performance status. Radiologic progression was documented in multiple sites including worsening tumor infiltration of his residual kidney. The patient was on palliative treatment and visited by the home hospice team in an end-of-life situation. The patient unexpectedly improved and went on to achieve a durable tumor response. The case is illustrative of an extreme manifestation of pseudoprogression, and impels us to probe the assumptions and controversies surrounding this phenomenon.

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Treatment Beyond Progression in Patients with Advanced Renal Cell Carcinoma Treated with Nivolumab in CheckMate 025

Cited by 208 publications

References 15 publications

Nivolumab treatment beyond RECIST‐defined progression in recurrent or metastatic squamous cell carcinoma of the head and neck in CheckMate 141: A subgroup analysis of a randomized phase 3 clinical trial

Nivolumab treatment beyond RECIST‐defined progression in recurrent or metastatic squamous cell carcinoma of the head and neck in CheckMate 141: A subgroup analysis of a randomized phase 3 clinical trial

Stereotactic body radiotherapy (SBRT) for pulmonary metastases from renal cell carcinoma—a multicenter analysis of the German working group “Stereotactic Radiotherapy”

Pushing the limits of immune-related response: a case of “extreme pseudoprogression”

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