Dataset Information

The association between body mass index and efficacy of pembrolizumab as second-line therapy in patients with recurrent/metastatic head and neck squamous cell carcinoma.

ABSTRACT:

Background

Recent evidence suggested a potential correlation between BMI and the efficacy of immune checkpoint inhibitors in cancer patients. This study aimed to evaluate the prognostic value of the body mass index (BMI) in recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC) patients treat with pembrolizumab.

Methods

The current retrospective cohort study enrolled 49 R/M HNSCC patients underwent at least one cycle of pembrolizumab as second-line treatment from June 2018 to October 2020. Survival analysis of immunotherapy prognosis and risk factor analysis of age, gender, BMI, ECOG-PS, CPS, rT-stage, tumor site, and tube feeding.

Results

Among the 49 patients, the BMI at the time of immunotherapy ranged from 14.5 to 32.0 kg/m² . The Kaplan-Meier analysis showed that the BMI was significantly correlated with overall survival time (OS, p = 0.0007) and progression-free survival time (PFS, p = 0.0012). BMI, gender, prior treatment, serum albumin level, ECOG-PS, CPS and rT-stage were analyzed in multivariate Cox regression model analysis after adjusted for potential confounding clinical variables. Patients with underweight (OS:HR = 6.862, 95% CI:1.566-30.064, p = 0.011; PFS:HR = 5.672, 95% CI:1.364-23.586, p = 0.017);ECOG≥2 (OS:HR = 0.250, 95% CI:0.086-0.731, p = 0.011;PFS:HR = 0.284, 95% CI:0.101-0.805, p = 0.018); CPS <1(OS: HR = 4.34, 95% CI:1.271-15.464, p = 0.019; PFS:HR = 3.859, 95% CI:1.180-12.618, p = 0.025) and rT4-stage(OS:HR = 4.380, 95% CI:1.452-13.209, p = 0.009;PFS: HR = 3.799, 95% CI:1.240-11.638, p = 0.019) suffered higher risk of mortality.

Conclusions

The BMI at the time of clinical diagnosis was showed to be an independent predictive factor for R/M HNSCC patients receiving pembrolizumab. Compared with normal weight patients, underweight patients have worse clinical prognosis.

SUBMITTER: Zhang X

PROVIDER: S-EPMC9939135 | biostudies-literature | 2022 Aug

REPOSITORIES: biostudies-literature

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Publications

The association between body mass index and efficacy of pembrolizumab as second-line therapy in patients with recurrent/metastatic head and neck squamous cell carcinoma.

Zhang Xinyi X Rui Mengyu M Lin Chao C Li Zhi Z Wei Dongliang D Han Ruxue R Ju Houyu H Ren Guoxin G

Cancer medicine 20220817 3

<h4>Background</h4>Recent evidence suggested a potential correlation between BMI and the efficacy of immune checkpoint inhibitors in cancer patients. This study aimed to evaluate the prognostic value of the body mass index (BMI) in recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC) patients treat with pembrolizumab.<h4>Methods</h4>The current retrospective cohort study enrolled 49 R/M HNSCC patients underwent at least one cycle of pembrolizumab as second-line treatment from J ...[more]

PMID: 35975731

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Project description:Anti-programmed cell death protein 1 (PD-1) therapy is a standard of care in recurrent metastatic head and neck squamous cell carcinoma (RMHNSCC). Vascular endothelial growth factor inhibitors, including tyrosine kinase inhibitors, have immunomodulatory properties and have offered promising results when combined with anti-PD-1 agents. We conducted a phase 2, multicenter, single-arm trial of pembrolizumab and cabozantinib in patients with RMHNSCC who had Response Evaluation Criteria in Solid Tumors v.1.1 measurable disease and no contraindications to either agent. We assessed the primary end points of tolerability and overall response rate to the combination with secondary end points of progression-free survival and overall survival and performed correlative studies with PDL-1 and combined positive score, CD8+ T cell infiltration and tumor mutational burden. A total of 50 patients were screened and 36 were enrolled with 33 evaluable for response. The primary end point was met, with 17 out of 33 patients having a partial response (52%) and 13 (39%) stable disease with an overall clinical benefit rate of 91%. Median and 1-year overall survival were 22.3 months (95% confidence interval (CI) = 11.7-32.9) and 68.4% (95% CI = 45.1%-83.5%), respectively. Median and 1-year progression-free survival were 14.6 months (95% CI = 8.2-19.6) and 54% (95% CI = 31.5%-72%), respectively. Grade 3 or higher treatment-related adverse events included increased aspartate aminotransferase (n = 2, 5.6%). In 16 patients (44.4%), the dose of cabozantinib was reduced to 20 mg daily. The overall response rate correlated positively with baseline CD8+ T cell infiltration. There was no observed correlation between tumor mutational burden and clinical outcome. Pembrolizumab and cabozantinib were well tolerated and showed promising clinical activity in patients with RMHNSCC. Further investigation of similar combinations are needed in RMHNSCC. The trial is registered at ClinicalTrials.gov under registration no. NCT03468218 .

Project description:BackgroundPembrolizumab, a PD-1 immune checkpoint inhibitor, is approved as first-line (1L) treatment for recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC) as monotherapy or in combination with platinum and 5-fluorouracil chemotherapy. Limited data exist on the use of these regimens in real-world settings.ObjectiveOur primary objectives were to describe baseline characteristics and real-world overall survival (rwOS), time on treatment (rwToT), and time to next treatment (rwTTNT) among individuals with R/M HNSCC receiving approved 1L pembrolizumab therapies. We also aimed to identify baseline factors associated with choice of 1L pembrolizumab therapy and with rwOS.MethodsThis was a retrospective cohort study of adults with R/M HNSCC receiving 1L pembrolizumab monotherapy or pembrolizumab plus chemotherapy. We used Kaplan-Meier analyses to assess real-world outcomes, logistic regression modeling to identify factors associated with choice of 1L pembrolizumab therapy, and Cox proportional hazards models to identify factors associated with rwOS.ResultsThe study population included 431 individuals receiving 1L pembrolizumab monotherapy and 215 receiving 1L pembrolizumab plus chemotherapy. The use of 1L pembrolizumab monotherapy was associated with higher baseline combined positive score for PD-L1 expression, older age, higher Eastern Cooperative Oncology Group performance status (ECOG PS), laryngeal tumor site, and human papillomavirus (HPV)-positive tumor status. The pembrolizumab monotherapy group had a median (95% CI) rwOS of 12.1 (9.2-15.1) months, rwToT of 4.2 (3.5-4.6) months, and rwTTNT of 6.5 (5.4-7.4) months. Among this group, HPV-positive tumor status and lower ECOG PS were associated with longer rwOS, and oral cavity tumor site with shorter rwOS. The pembrolizumab plus chemotherapy cohort had a median (95% CI) rwOS of 11.9 (9.0-16.0) months, rwToT of 4.9 (3.8-5.6) months, and rwTTNT of 6.6 (5.8-8.3) months. In this group, HPV-positive tumor status was associated with longer rwOS.ConclusionsThis study adds to clinical trial data by summarizing real-world treatment outcomes with 1L pembrolizumab-containing therapies in a more heterogeneous population. Overall survival outcomes in both treatment groups were similar to those observed in the registration clinical trial. These findings support the use of pembrolizumab as standard of care for R/M HNSCC.

Project description:BackgroundIn the phase III LUX-Head & Neck 1 (LHN1) trial, afatinib significantly improved progression-free survival (PFS) versus methotrexate in recurrent and/or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) patients progressing on/after platinum-based therapy. This report evaluates afatinib efficacy and safety in prespecified subgroups of patients aged ≥65 and <65 years.Patients and methodsPatients were randomized (2:1) to 40 mg/day oral afatinib or 40 mg/m(2)/week intravenous methotrexate. PFS was the primary end point; overall survival (OS) was the key secondary end point. Other end points included: objective response rate (ORR), patient-reported outcomes, tumor shrinkage, and safety. Disease control rate (DCR) was also assessed.ResultsOf 483 randomized patients, 27% (83 afatinib; 45 methotrexate) were aged ≥65 years (older) and 73% (239 afatinib; 116 methotrexate) <65 years (younger) at study entry. Similar PFS benefit with afatinib versus methotrexate was observed in older {median 2.8 versus 2.3 months, hazard ratio (HR) = 0.68 [95% confidence interval (CI) 0.45-1.03], P = 0.061} and younger patients [2.6 versus 1.6 months, HR = 0.79 (0.62-1.01), P = 0.052]. In older and younger patients, the median OS with afatinib versus methotrexate was 7.3 versus 6.4 months [HR = 0.84 (0.54-1.31)] and 6.7 versus 6.2 months [HR = 0.98 (0.76-1.28)]. ORRs with afatinib versus methotrexate were 10.8% versus 6.7% and 10.0% versus 5.2%; DCRs were 53.0% versus 37.8% and 47.7% versus 38.8% in older and younger patients, respectively. In both subgroups, the most frequent treatment-related adverse events were rash/acne (73%-77%) and diarrhea (70%-80%) with afatinib, and stomatitis (43%) and fatigue (31%-34%) with methotrexate. Fewer treatment-related discontinuations were observed with afatinib (each subgroup 7% versus 16%). A trend toward improved time to deterioration of global health status, pain, and swallowing with afatinib was observed in both subgroups.ConclusionsAdvancing age (≥65 years) did not adversely affect clinical outcomes or safety with afatinib versus methotrexate in second-line R/M HNSCC patients.Clinical trial registrationNCT01345682 (ClinicalTrials.gov).

Project description:BackgroundThe optimal second-line systemic treatment model for recurrent and/or metastatic head and neck squamous cell carcinoma (R/M HNSCC) remains controversial. A Bayesian network meta-analysis (NMA) was performed to address this issue with regard to efficacy and toxicity.MethodsBy searching MEDLINE (via PubMed), Embase, the Cochrane Central Register of Controlled Trials and Web of Science, we extracted eligible studies. Efficacy, represented as overall survival (OS) and progression-free survival (PFS), and overall toxicity, represented as ≥ grade 3 severe acute events (sAE), were assessed to compare the following 7 treatment models through an NMA: standard-of-care therapy (SoC), single targeted therapy different from SoC (ST), double targeted therapy (DT), targeted therapy combined with chemotherapy (T+C), single immune checkpoint inhibitor therapy (SI), double immune checkpoint inhibitor therapy (DI) and single chemotherapy different from SoC (SC). Rank probabilities according to the values of the surface under the cumulative ranking curve (SUCRA) were separately determined for efficacy and toxicity.ResultsIn total, 5285 patients from 24 eligible studies were ultimately screened, with 5184, 4532 and 4026 involved in the NMA of OS, PFS and sAE, respectively. All qualifying studies were absent from first-line immune checkpoint inhibitor therapy. In terms of OS, SI was superior to the other treatments, followed by DI, ST, T+C, SoC, DT and SC. Other than SI and SC, all treatments tended to be consistent, with hazard ratios (HRs) close to 1 between groups. For PFS, ST ranked first, while DT ranked last. For the toxicity profiles, compared with the other models, SI resulted in the lowest incidences of sAE, with statistical significance over SoC (odds ratio [OR] 0.31, 95% credible interval [CrI] 0.11 to 0.90), ST (OR 0.23, 95% CrI 0.06 to 0.86) and DT (OR 0.11, 95% CrI 0.02 to 0.53), while DT was the worst. When the SUCRA values of OS and sAE were combined, a cluster plot illustrated the superiority of SI, which demonstrated the best OS and tolerability toward sAE.ConclusionFor R/M HNSCC patients without immune checkpoint inhibitors in the first-line setting, SI may serve as the optimal second-line systemic treatment model, demonstrating the best OS and least sAE.

Dataset Information

The association between body mass index and efficacy of pembrolizumab as second-line therapy in patients with recurrent/metastatic head and neck squamous cell carcinoma.

Background

Methods

Results

Conclusions

Publications

The association between body mass index and efficacy of pembrolizumab as second-line therapy in patients with recurrent/metastatic head and neck squamous cell carcinoma.

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