Response rates and survival to systemic therapy after immune checkpoint inhibitor failure in recurrent/metastatic head and neck squamous cell carcinoma

Pestana, Roberto Carmagnani; Becnel, Melody; Rubin, Maria Laura; Torman, Danice K.; Crespo, James; Phan, Jack; Hanna, Ehab Y.; Bell, Diana; Glisson, Bonnie S.; Johnson, Jason M.; Lee, John

doi:10.1016/j.oraloncology.2019.104523

Cited by 48 publications

(43 citation statements)

References 33 publications

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“…Retrospective series and case reports in lung cancer and in other entities have shown increased responses to salvage chemotherapy after immunotherapy (SCAI) [9][10][11][12][13][14][15][16][17][18]. However, data demonstrating such responses in SCCHN are still limited, particularly when using anti-EGFR-based chemotherapy [13,16,[19][20][21][22][23][24]. Our aim was to retrospectively study the safety and efficacy of salvage chemotherapy combined with cetuximab after progression to ICIs in patients with R/M SCCHN.…”

Section: Introductionmentioning

confidence: 99%

Safety and Efficacy of Cetuximab-Based Salvage Chemotherapy After Checkpoint Inhibitors in Head and Neck Cancer

et al. 2021

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Background. There are still few data on the activity and safety of cetuximab-based salvage chemotherapy after immunotherapy (SCAI) in patients with squamous cell cancer of the head and neck (SCCHN). Materials and Methods. Retrospective study of patients with SCCHN who received cetuximab-based SCAI after PD1 or PDL1 (PD(L)1) inhibitors. Overall response rate (ORR) and disease control rate (DCR) with SCAI and with last chemotherapy before immunotherapy (LCBI) by RECIST 1.1, percentage change from baseline in target lesions (PCTL), progression-free survival (PFS), overall survival (OS), treatment compliance and toxicity were evaluated. Results. Between March 2016 and November 2019, 23 patients were identified. SCAI consisted of cetuximabbased combinations (3wkCDDP-5FU-Cetuximab (n=2), wkPaclitaxel-Cetuximab (n=17), wkCDDP-Cetuximab (n=2), wkCBDCA-Paclitaxel-Cetuximab (n=2)). ORR was 56.5% (11 partial response (PR), 2 complete response (CR)). DCR was 78.3%. Among 13 objective responders, median best PCTL was-53.5% (range:-30% to-100%). Median OS and PFS were 12m and 6m, respectively. In 10 patients receiving LCBI, ORR to LCBI was 40%, while ORR to SCAI achieved 60%. In LCBI-treated patients median PFS with LCBI was 8m and median PFS and OS with SCAI were 7m and 12m, respectively. Reduced dose intensity of the chemotherapy and cetuximab components occurred in 82.6% and 52.2% of the patients. Grade 1 or 2 AEs occurred in all patients. Grade 3 or 4 AEs developed in 65%, being grade 3 in all of them except in one patient (grade 4 neutropenia). There were no treatment-related deaths. Conclusion. Cetuximab-based salvage chemotherapy after PD(L)1 inhibitors associated with high response rates and deep tumor reductions with a manageable safety profile. Subsequent lines of therapy may explain the long survival achieved in our series. These results invite to design studies to elucidate the best therapeutic sequence in patients with SCCHN in the immunotherapy era. The Oncologist 2021;9999:• • Implications for Practice: Cetuximab-based salvage chemotherapy (SCAI) achieved high response rates in patients with R/M SCCHN after progression to PD1/PDL1 inhibitors. Objective response rate was higher and progression-free survival was comparable to that of chemotherapy administered before immunotherapy (IO). In most patients, SCAI consisted of weekly, welltolerated regimens. These observations have implications for current practice due to the limited evidence to date in SCCHN and the scant therapeutic options in this disease, and invite to elucidate which may be the best treatment sequence for head and neck cancer patients in the IO era.

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Section: Introductionmentioning

confidence: 99%

Safety and Efficacy of Cetuximab-Based Salvage Chemotherapy After Checkpoint Inhibitors in Head and Neck Cancer

et al. 2021

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“…Several studies have reported that salvage chemotherapy (SCT) administered after immunotherapy would be effective for patients with metastatic non-small-cell lung cancer (NSCLC), metastatic melanoma, B cell lymphoma, advanced gastric cancer, and metastatic urothelial carcinoma [ 3 , 4 , 5 , 6 , 7 , 8 , 9 ]. Furthermore, SCT has been reported to be an effective treatment for HNSCC in R/M as well as other carcinomas and is attracting attention as a sequential treatment [ 10 , 11 ]. Currently, combination chemotherapy of weekly paclitaxel and cetuximab (PC) or oral tegafur-gimestat-otastat potassium (S1) is administered as SCT after ICI treatment in our institution and associated facilities.…”

Section: Introductionmentioning

confidence: 99%

Prognostic Biomarkers of Salvage Chemotherapy Following Nivolumab Treatment for Recurrent and/or Metastatic Head and Neck Squamous Cell Carcinoma

Wakasaki

Yasumatsu

Masuda

et al. 2020

Cancers

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Recent studies have suggested the benefit of salvage chemotherapy (SCT) after immune checkpoint inhibitor (ICI) treatment for recurrent and metastatic head and neck squamous cell carcinoma (R/M HNSCC). We retrospectively examined the outcome of SCT and the usefulness of the serum C-reactive protein level (CRP) and neutrophil-to-lymphocyte ratio (NLR) as prognostic biomarkers. Thirty-nine patients with R/M HNSCC were enrolled in this study. Twenty-five patients (64.1%) received combination chemotherapy of weekly paclitaxel and cetuximab (PC) as SCT, and 14 patients (35.9%) received tegafur-gimestat-otastat potassium (S1), an oral fluoropyrimidine. In all patients, the response rate, disease control rate, median progression-free survival (PFS), and median overall survival (OS) were 45.2%, 85.7%, 6.5 months, and 13.5 months, respectively. No chemotherapy-related deaths were observed. These PC groups had low CRP (<1.2 mg/dL) or low NLR (<7.0) values at the time of SCT induction, which was significantly associated with an improved OS (p = 0.0440, p = 0.0354). A multivariate analysis also showed that a lower CRP value was significantly associated with a better OS (p = 0.0078). We clarified the usefulness of the PC and S1 regimens as SCT. In addition, SCT with the PC regimen showed a better prognosis with a lower CRP or NLR at induction than a higher CRP or NLR. This is the first report on biomarkers of SCT in R/M HNSCC.

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“…14,15 Immune checkpoint inhibitors have also shed light on the treatment of OSCC, and inflammation and immunity have been involved in the development of OSCC. 16 However, the immunological characteristics of OSCC are still largely uncovered.…”

Section: Discussionmentioning

confidence: 99%

<p>Inflammatory Marker Predicts Outcome of Oral Squamous Cell Carcinoma Receiving Chemo-Radiotherapy</p>

Sun

Gao

2020

CMAR

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Background: Inflammation is involved in the progression of oral squamous cell carcinoma. We therefore postulate that a blood-based inflammatory marker, the neutrophil-tolymphocyte ratio, could help to predict the prognosis in patients with oral squamous cell carcinoma receiving chemo-radiotherapy, and build a prognostic nomogram. Methods: In 111 cases of oral squamous cell carcinoma, several baseline variables, including inflammatory markers and lactate dehydrogenase, were measured within the week of chemoradiotherapy initiation as predictors of mortality and separate risk scores were developed. Results: Dichotomized neutrophil-to-lymphocyte ratio was found to be associated with AJCC stage (p<0.001). Patients with oral squamous cell carcinoma with a low neutrophil-tolymphocyte ratio survived longer than those with a high neutrophil-to-lymphocyte ratio (overall survival HR=2.39, 95% CI 1.24-4.61, p=0.009). The Harrell's concordance (C)-statistic of the nomogram was 0.74 and the calibration curve demonstrated the goodness of fit. Conclusion: The inflammatory marker neutrophil-to-lymphocyte ratio, obtained before chemo-radiotherapy, was an independent factor of survival prediction for oral squamous cell carcinoma. The nomogram incorporating immunological markers could more accurately predict individualized survival probability than the existing models. These findings are significant for the creation of personalized treatment strategies in the clinical setting.

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Response rates and survival to systemic therapy after immune checkpoint inhibitor failure in recurrent/metastatic head and neck squamous cell carcinoma

Cited by 48 publications

References 33 publications

Safety and Efficacy of Cetuximab-Based Salvage Chemotherapy After Checkpoint Inhibitors in Head and Neck Cancer

Safety and Efficacy of Cetuximab-Based Salvage Chemotherapy After Checkpoint Inhibitors in Head and Neck Cancer

Prognostic Biomarkers of Salvage Chemotherapy Following Nivolumab Treatment for Recurrent and/or Metastatic Head and Neck Squamous Cell Carcinoma

<p>Inflammatory Marker Predicts Outcome of Oral Squamous Cell Carcinoma Receiving Chemo-Radiotherapy</p>

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