Abstract CT157: Treatment beyond progression with nivolumab in patients with recurrent or metastatic squamous cell carcinoma of the head and neck in the phase 3 Checkmate 141 study
Authors: Haddad Robert , Ferris Robert L. , Blumenschein George , Fayette Jerome , Guigay Joel , Colevas Alexander D. , Licitra Lisa , Kasper Stefan , Vokes Everett E. , Worden Francis , Saba Nabil F. , Tahara Makoto , Monga Manish , Lynch Mark , Zhu Jin , Shaw James W. , Gillison Maura L. , Harrington Kevin 
Published: July 2017

Abstract
Background: Responses in patients (pts) treated with immune checkpoint inhibitors may occur after initial evidence of radiological disease progression. In CheckMate 141, a randomized phase 3 study of nivolumab (nivo) vs investigator’s choice (IC) of standard single-agent therapy in recurrent or metastatic (R/M) squamous cell carcinoma of the head and neck (SCCHN), nivo demonstrated prolonged OS compared with IC therapy, hazard ratio = 0.70 (97.73% confidence interval [CI]: 0.51, 0.96). Grade 3-4 treatment-related adverse events (TRAEs) occurred in 13.1% of nivo-treated pts and 35.1% of IC-treated pts. Patient-reported quality of life was stable with nivo and worsened with IC therapy. Here we assessed safety and efficacy in pts treated beyond progression (TBP) with nivo in CheckMate 141.
Methods: Treatment beyond investigator-assessed RECIST 1.1-defined progression was permitted in pts in the nivo arm if all criteria prespecified in the protocol were met. Otherwise, pts were not treated beyond progression and discontinued treatment after first progression. Pts without progression, or those who died or discontinued without a tumor assessment to determine progression, were excluded from this analysis.
Results: Of the 240 pts randomized to nivo, 139 (58%) experienced RECIST-defined disease progression. Among these pts, 57 (41%) received ≥1 subsequent dose of nivo after progression (TBP group), and 82 (59%) were not treated beyond progression (NTBP group). The mean duration of treatment beyond progression was 2.0 months (range: 0, 9). Median OS was 12.7 months (95% CI: 9.7, not reached) in the TBP group and 6.1 months (95% CI: 4.8, 7.8) in the NTBP group. The objective response rate from randomization to initial progression was 12.3% and 4.9% for the TBP and NTBP groups, respectively; 31.6% and 19.5% of pts, respectively, had stable disease. After initial progression, 13 pts (23%) in the TBP group had tumor burden reduction, with &gt;30% reduction in 2 pts. Of these 13 pts, 7 were HPV+, 3 were PD-L1+, and 4 had ≥20% tumor size increase at first progression. In the TBP and NTBP groups, select TRAEs were similar, with a higher frequency of skin/subcutaneous tissue disorders in the TBP group (29.8% and 11.0%; none were grade 3-4). Select endocrine TRAEs occurred in 10.5% (TBP) and 8.5% (NTBP) of pts; none were grade 3-4. Grade 3-4 TRAEs occurred in 12.3% and 13.4% of pts in the TBP and NTBP groups, respectively. Patient-reported quality of life from randomization through week 21 was generally stable in the TBP group, consistent with trends observed in the overall nivo-treated population. Additional analyses to further characterize TBP and NTBP pts will be presented.
Conclusions: These results suggest that nivo treatment beyond RECIST-defined disease progression was tolerable in R/M SCCHN, with some pts experiencing tumor reduction after initial progression.
Citation Format: Robert Haddad, Robert L. Ferris, George Blumenschein, Jerome Fayette, Joel Guigay, Alexander D. Colevas, Lisa Licitra, Stefan Kasper, Everett E. Vokes, Francis Worden, Nabil F. Saba, Makoto Tahara, Manish Monga, Mark Lynch, Jin Zhu, James W. Shaw, Maura L. Gillison, Kevin Harrington. Treatment beyond progression with nivolumab in patients with recurrent or metastatic squamous cell carcinoma of the head and neck in the phase 3 Checkmate 141 study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr CT157. doi:10.1158/1538-7445.AM2017-CT157