Recurrent Metastatic Head Research Articles

Baseline eosinophil proportion is a useful predictor of immune-related adverse events following immune checkpoint inhibitor treatment for recurrent metastatic head and neck cancer

Background Immune checkpoint inhibitors (ICIs) occasionally cause immune-related adverse events (irAEs) in various organs. However, predictors of irAEs remain unidentified. Objectives We evaluated the predictors of irAEs and compared the outcomes of ICIs with and without irAEs in patients with recurrent/metastatic head and neck cancers (R/M HNCs). Materials and methods We retrospectively analyzed 157 patients with R/M HNCs who were administered an anti-PD-1 antibody between September 2014 and December 2022. We examined whether various pretreatment factors were associated with irAEs. The overall survival (OS) and progression-free survival (PFS) in patients with and without irAEs were analyzed. Results Overall, 44 patients (28.0%) developed irAEs. The survival curve estimated for patients with and without irAEs showed a significant difference in PFS (p = 0.018), but not in OS (p = 0.208). Multivariate analysis revealed significant differences in relative eosinophil counts (p < 0.001), TP (p = 0.014), and NLR (p = 0.002), which may be independent predictors of irAEs. Conclusion IrAEs may be associated with higher efficacy of ICIs and longer PFS. The relative eosinophil count may be predictors of irAEs and useful in routine medical practice. Using these biomarkers to predict irAEs will help predict ICI effects and manage irAEs.

Effect of Nivolumab on the Quality of Life in Recurrent/Metastatic Head and Neck Cancer.

Nivolumab is expected to further prolong survival and improve the quality of life (QOL) of patients with a poor prognosis of head and neck cancer. However, only a few studies have been conducted regarding the QOL of recurrent or metastatic head and neck cancer patients treated with nivolumab using real-world data. This study aimed to examine the effect of nivolumab on the QOL of these patients using real-world data. This study included patients with recurrent metastatic head and neck cancer who received nivolumab at the Department of Otolaryngology and Head and Neck Surgery, Tokyo Medical University Hospital from May 1, 2017, to December 31, 2021. Among them, 50 patients who self-assessed their QOL were included in this study. The primary endpoint was the QOL evaluation score, and secondary endpoints were overall survival (OS), progression-free survival (PFS), response rate, and immune-related adverse events. OS and PFS were evaluated using the Kaplan-Meier method. No significant reduction in QOL was observed before or after nivolumab administration. The median OS time was 20.1 months, and 1-year OS rate was 76.4%. The median PFS time was 4.2 months, and 1-year PFS rate was 31.0%. The comparison of patient QOL before and after nivolumab use suggested that patient QOL was not compromised. The results were not inferior to those of other studies in terms of treatment efficacy and safety.

Updates to Treatment of Recurrent Metastatic Head and Neck Cancers

Updates to Treatment of Recurrent Metastatic Head and Neck Cancers

Pembrolizumab and Cabozantinib in Recurrent Metastatic Head and Neck Squamous Cell Carcinoma (RMHNSCC): 2-year Long Term Survival Update with Biomarker Analysis

Pembrolizumab and Cabozantinib in Recurrent Metastatic Head and Neck Squamous Cell Carcinoma (RMHNSCC): 2-year Long Term Survival Update with Biomarker Analysis

863P Microbiota and cytokines profile in patients (pts) affected by recurrent metastatic head and neck squamous cell carcinoma (R/M HNSCC) treated with immune checkpoint inhibitors (ICIs) +/- chemotherapy (CT) and prebiotic inulin in the PRINCESS study

863P Microbiota and cytokines profile in patients (pts) affected by recurrent metastatic head and neck squamous cell carcinoma (R/M HNSCC) treated with immune checkpoint inhibitors (ICIs) +/- chemotherapy (CT) and prebiotic inulin in the PRINCESS study

A Prospective Observational Study of Proton Stereotactic Body Radiation Therapy and Immunotherapy for Recurrent Metastatic Head and Neck Cancer: Initial Report of MC ROR1771 Survival Analysis and Toxicity

<h3>Purpose/Objective(s)</h3> Patients with recurrent head and neck squamous cell carcinoma (HNSCC) after previous platinum-based chemotherapy have a median survival of 6 months or less. CheckMate 141 demonstrated that nivolumab administration to this patient population led to a median 7.5-month survival vs. 5.1-months with standard therapy, with 36% 1-year overall survival. The effect of radiotherapy on tumor immunogenicity when combined with immunotherapy has been an area of interest in immuno-oncology. However, proton therapy's role in this space is not well understood. MC ROR1771 was designed as a multisite prospective observational study to evaluate the addition of stereotactic body proton therapy (SBPT) to nivolumab in a platinum-refractory population. <h3>Materials/Methods</h3> Patients with metastatic histologically confirmed HNSCC from any primary site were eligible. Two cycles of nivolumab every other week were followed by SBPT to 1-2 target lesion(s). Maintenance nivolumab continued every other week with follow-up for progression and treatment toxicity. Subsequent oligoprogression was treated with stereotactic body radiotherapy or SBPT as indicated. Objective criteria included target lesion response rate, overall survival, progression-free survival, time to distant metastasis, toxicity, and evaluation of potential predictive biomarkers. Survival analysis was conducted using the Kaplan-Meier method in statistical software. The focus of this report was survival and toxicity analyses. <h3>Results</h3> 15 patients enrolled with 13 receiving SBPT, after which one treated patient withdrew. Of the remaining twelve, 3 had laryngeal primary, 1 nasopharyngeal, and 8 oropharyngeal. 4 patients underwent one round of prior chemotherapy before enrollment, 3 patients two rounds, and 5 patients three rounds: 10 received concurrent chemoradiation in first line (5 definitive, 5 adjuvant), with 1 receiving neoadjuvant chemotherapy prior to chemoradiation, and one presenting with metastatic disease. SBPT dosing ranged from 35-50 Gy. From initiation of nivolumab, median overall survival was 12.5 months (1-year overall survival 67%), with median progression free survival of 4.5 months. Two patients presented with baseline grade 3 cancer pain; no ≥grade 3 toxicity specific to nivolumab nor SBPT was reported. One patient is still alive at 40 months from initiation of nivolumab. <h3>Conclusion</h3> In this highly pretreated population, overall and progression-free survival compare favorably with CheckMate 141, suggesting that SBPT co-treatment may be beneficial in this population. No ≥grade 3 toxicity occurred with nivolumab nor SBPT. Biochemical analysis and correlation with delineated local, regional, and distant radiographic response are forthcoming. Further prospective evaluation of combination SBPT and immunotherapy is needed.

Gut microbiome/metabolome predicts response to immune checkpoint blockers (ICB) in patients with recurrent metastatic head and neck squamous cell cancer (RM HNSCC).

6055 Background: Gut microbiome has emerged as an important predictor of response to ICB therapy in various cancers, most notably in melanoma. Due to functional redundancy of microbiota, there has been lack of consistency in gut microbial signature associated with ICB response. Microbial metabolites in addition to taxonomy may play a superior role in predicting response to ICB. Gut microbiome/metabolome signatures of ICB response is unknown in RM HNSCC patients. Methods: Two cohorts of patients were included (stool and plasma samples were collected)- cohort 1, newly diagnosed RM HNSCC patients starting first line ICB, for whom samples were collected before ICB initiation (baseline) and post-treatment at 3, 6, and 12 months. Cohort 2 with durable response (disease control lasting ≥ 6 months), with single sample collected at study entry. 16s rRNA sequencing was performed on stool samples while plasma metabolites were quantitated using Q Exactive plus Orbitrap mass spectrometer. Response was defined as partial response (PR) or complete response (CR) as per RECIST 1.1 Results: The 16-S sequence was carried on 31 samples (cohort 1- 16 baseline, 7 post treatment; cohort 2- 8 durable responders). Targeted metabolomics was completed on 92 plasma samples [cohort 1-27 baseline and 50 post-treatment, cohort 2- 15]. Responders had a significantly higher Shannon’s diversity index, lower Fermicutes to Bacteroidetes ratio, and were enriched with genus Bacteroides and Lachnospiracea incerate sedis at baseline and post treatment, compared to non-responders (p &lt; 0.05). At species level, baseline and post treatment microbiome of responders was enriched with Eubacterium oxidoreducens and Bacteroides uniformis. Ruminococcus was preferentially enriched in durable responders. Targeted analysis of plasma metabolites (associated with gut microbial metabolism) showed that responders had a significantly lower baseline adenosine, Inosine and xanthine level as compared to non responders. Further, Inosine levels decreased with response, while levels increased in non-responders (p &lt; 0.05), suggestive of consumption by re-activated T cells Further, ICB responders had significantly lower Kynurenine to tryptophan ratio compared to non responders Conclusions: This is the first study evaluating association of gut microbiome and metabolome on response to first line ICB, in RM HNSCC patients. We found higher diversity and specific gut microbial signatures associated with ICB response. Interestingly, we found that inosine and kynurenine/tryptophan pathways, both which play a crucial role in host as well as gut microbial metabolism were differentially expressed in ICB responders. Our results if validated in larger cohort, lays groundwork for gut microbiome and importantly microbial metabolite modulation to improve response to ICB in RM HNSCC.

A phase II trial of pembrolizumab and cabozantinib in patients (pts) with recurrent metastatic head and neck squamous cell carcinoma (RMHNSCC).

6008 Background: Pembrolizumab (pembro) is an immune checkpoint inhibitor (ICI) approved for treating pts with recurrent/metastatic (RM) HNSCC. Cabozantinib (cabo) is a multiple receptor tyrosine kinase inhibitor (TKI) targeting MET and VEGFR2 shown to reduce tumor growth, metastasis, and angiogenesis and has immuno-modulatory properties. Methods: This is a phase II, open label multi-center, single arm trial evaluating the tolerability and clinical benefit of pembro administered at 200 mg every 3 weeks and cabo 40 mg daily for pts with RM HNSCC who have not received prior ICI. It had a lead-in safety cohort allowing reduction of cabo dose to 20mg daily. Eligible pts had RM HNSCC, deemed incurable, with a tumor PD-L1 CPS &gt; 1, RECIST 1.1 measurable disease, a life expectancy of &gt; 3 months, an Eastern Cooperative Group (ECOG) Performance Status (PS) of 0-1. Enrollment was initiated in March of 2019. We estimated that the ORR will improve to 35% with pembro+ cabo (from a historic of 18%) with a significance level of 0.05 and 80% power. Results: A total of 47 pts were screened, 13 screen failures [cavitation on scan (4), inability to swallow pills (2), other exclusions (7)]; 34 pts were enrolled, 32 were dosed and 31 evaluable (at least one follow-up scan). Pts had cancers of the oropharynx (21, 65%), nasopharynx (6, 19%), larynx/hypopharynx (4, 13%) and oral cavity (1,3%). 32 patients received cabo at 40 mg daily; 13 patients (41%) were dose reduced to 20mg daily [mucositis, increased liver function (LFT) tests, diarrhea]; males (n=29, 90%), median age 63 years (range 53-67); presence of distant metastases (34, 100%); prior radiation (29, 90%), chemotherapy (14, 43%); ECOG PS =0 (16, 50%), 1 (16,50%); HPV/p16 positive (17, 53%), negative (5, 16%), not applicable (10, 29%); the most frequent adverse event (AE) (all grades) was fatigue (16,50.0%), grade 3 or 4 treatment-related AE were increased LFTs, hyponatremia (3, 9.3% each). With a median follow up of 12.7 months (mos) (range 6.9- 20.5 mos), a RECIST 1.1 overall response rate ORR= 45.2% (CR=0; PR=14, 45.2%; SD =14, 45.2%; PD=3.0, 10%) with an overall clinical benefit of 90.4% were observed; The 1-yr OS was 67.7% (95% CI, 42.9%-83.6%; median 22.3 mos) and 1-yr PFS was 51.8% (95% CI, 28.8%-70.7%; median 14.6 mos). Conclusions: This phase II trial of pembro + cabo met its primary endpoint of ORR. The regimen is well-tolerated with very encouraging clinical activity in RM HNSCC and warrants further exploration in this disease. The study was supported by a grant from Exelixis to NFS. Clinical trial information: NCT03468218.

Impact of Tobacco, Marijuana and Alcohol Use on Overall Survival in Recurrent Metastatic Head and Neck Cancer Patients Treated with Immune Checkpoint Inhibitors

<h3>Purpose/Objective(s)</h3> Tobacco, marijuana, and alcohol use have all been associated with immune suppressive effect. This study assess the impact of smoking status, marijuana use and alcohol consumption on overall survival (OS) in patients (pts) with recurrent-metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) treated with immune checkpoint inhibitors (ICI). <h3>Materials/Methods</h3> Between January 15^th 2016 and April 9^th 2020, 201 pts with R/M HNSCC were treated with ICI. Data on smoking status, marijuana use and alcohol consumption were collected through retrospective chart review. We had p16 status, hemoglobin, albumin, lactate dehydrogenase (LDH), neutrophil, lymphocyte and platelet count recorded initially at the time of starting ICI. OS was defined from the start of ICI to death. Progression Free Survival (PFS) was defined from the start of ICI to disease progression (PD) or death. <h3>Results</h3> 201 pts were analyzed, sex: 154 male (77%), 47 female (23%). Median age 61 (IQR: 55-68). ICI drug: pembrolizumab 100 (50%), nivolumab 91 (45%), ipilimumab+nivolumab 10 (5%). Line of therapy: first: 98 (49%), second and beyond: 103 (51%). Tumor site: oropharynx 84 (42%), oral cavity 45 (22%), others 72 (36%). p16 status: negative 132 (66%), positive 69 (34%). Smoking status: former 111 (55%), never 54 (27%), current 36 (18%), median pack-year 18 (IQR: 0-37). Alcohol use: yes 110 (55%), no 91 (54%). Marijuana use: yes 47 (23%), no 154 (77%). Laboratory values: median neutrophil count: 4.58 (IQR: 3.43-6.47), median lymphocyte count: 0.69 (IQR: 0.47-1.08), median platelet count: 229 (IQR: 187-300), hemoglobin: normal/low 101/100 (50%/50%), albumin: normal/low 156/45 (78%/22%), LDH: normal/high 124/77 (62%/38%). Overall response rate: 36 (18%). Median OS: 12 months (CI: 9.4-14.8), median PFS: 4 months (CI: 3.5-5.7). Tobacco: former [HR 0.92 (0.62-1.36), <i>p=0.3</i>], current [HR 0.66 (0.39-1.14), <i>p=0.3</i>]. Marijuana: yes [HR 0.66 (0.43-1.01), <i>p=0.054</i>]. Alcohol: yes [HR 0.91 (0.65-1.28), <i>p=0.6</i>]. The variables associated with OS were high neutrophil count [HR 1.28 (1.08 – 1.51), <i>p=0.004</i>], high lymphocyte count [HR 0.75 (0.60 – 0.95), <i>p=0.015</i>], albumin (low) [HR 2.06 (1.37 – 3.10), <i>p<0.001</i>], hemoglobin (low) [HR 1.64 (1.14 – 2.35), <i>p=0.007</i>], LDH (high) [HR 1.78 (1.23 – 2.56), <i>p=0.002</i>] and p16 status (positive) [HR 0.58 (0.39-0.87), <i>p=0.009</i>]. <h3>Conclusion</h3> In our single institutional cohort, smoking status, marijuana use and alcohol consumption did not appear to have a significant impact on OS in patients with R/M HNSCC treated with ICI. As we previously reported, the pre-treatment patient characteristics associated with OS include neutrophil count, lymphocyte count, hemoglobin, albumin, LDH and p16 status.

Clinical Outcomes of Cetuximab and Paclitaxel after Progression on Immune Checkpoint Inhibitors in Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma.

Background and Objectives: In recent years, the effectiveness of chemotherapy after immune checkpoint inhibitor administration has attracted attention in various cancers, including head and neck cancers. However, individual assessments of the administered chemotherapy regimens are insufficient. This study aimed to evaluate the efficacy and safety of chemotherapy after immune checkpoint inhibitor administration in recurrent metastatic head and neck cancer by focusing on a single regimen. Materials and Methods: We retrospectively reviewed clinical and radiological data from the medical records of 18 patients with recurrent or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) who received systemic chemotherapy with weekly cetuximab and paclitaxel (Cmab + PTX) after progression following immune checkpoint inhibitor (ICI) therapy. The objective response rate (ORR) and disease control rate (DCR) were assessed using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan–Meier method. Adverse events (AEs) were recorded using National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.0. Results: In all patients, the ORR, DCR, median PFS, and median OS were 44.4%, 72.2%, 3.8 months, and 9.6 months, respectively. Regarding AEs, three patients developed grade 3 neutropenia. Grade 3 anemia, paronychia, asthenia, and peripheral neuropathy were observed in one patient each. There were no treatment-related deaths. Conclusions: Cmab + PTX was shown to maintain high efficacy and acceptable safety for R/M HNSCC that progressed after ICI therapy. Further research is needed to establish optimal treatment sequences and drug combinations for recurrent R/M HNSCC.

Use of cetuximab added to weekly chemotherapy to improve progression-free survival in patients with recurrent metastatic head and neck squamous cell carcinoma after progression on immune checkpoint inhibitors.

6038 Background: Immune checkpoint inhibitors (ICI) are currently approved in the treatment of patients (pts) with recurrent-metastatic (R/M) head and neck squamous cell carcinoma (HNSCC). The majority of pts will progress on ICI. Little is known regarding the best treatment approach for this patient population. We previously showed that the combination of weekly carboplatin, paclitaxel and cetuximab was associated with reduced risk of grade 3/4 toxicities, which makes it an ideal regimen in this setting. Here; we report the outcomes of pts with R/M HNSCC who were treated with chemotherapy alone vs weekly chemotherapy plus cetuximab after progression on ICI. Methods: Between January 15th 2016 and April 9th 2020, 154 pts who progressed on ICI were analyzed. Among these pts, 64 had received subsequent systemic therapy and met the inclusion criteria. Progression Free Survival (PFS) was defined as the time elapsed between initiation of subsequent chemotherapy and tumor progression or death. Overall Survival (OS) was defined as the time elapsed between initiation of subsequent chemotherapy to death. Descriptive statistics and Cox regression were used to explore study variables. Results: 64 pts received subsequent chemotherapy after progression on ICI. 28 pts (44%) received a combination of weekly chemotherapy plus cetuximab. This regimen included carboplatin AUC 1.5, paclitaxel 45 mg/m2, and cetuximab loading dose of 400mg/m2 followed by weekly dose of 250 mg/m2. 36 pts (56%) received chemotherapy alone without cetuximab. These regimens included capecitabine, afatinib, and gemcitabine, among others. Sex: 51 males (80%), 13 females (20%), age (median): 61 (IQR: 53-66), tumor site: oropharynx 32 (50%), oral cavity 11 (17%), larynx 8 (12%), other sites 13 (21%). P16 status: negative 36 (56%), positive 28 (44%). Prior ICI drug: pembrolizumab 34 (53%), nivolumab 26 (41%), ipilimumab + nivolumab 4 (6%). Median follow up: 9 months (IQR: 5-13). Overall response rate: weekly chemotherapy plus cetuximab 32%, chemotherapy alone 22% (p = 0.4). Pts who received chemotherapy alone had a median PFS of 3.2 months (CI: 2-5) vs 5.6 months (CI: 4.3-10.1) in the weekly chemotherapy plus cetuximab group. After adjusting for p16 status and prior ICI drug, PFS was improved in the group that received weekly chemotherapy plus cetuximab vs. chemotherapy alone (HR: 0.52; CI: 0.28-0.98; p = 0.042). Median OS was 10 months (CI: 8.5-NR) in the weekly chemotherapy plus cetuximab group vs 8.7 months (CI: 5.7-13.8) in the chemotherapy alone group (HR: 0.84; CI: 0.4-1.8; p = 0.8). Conclusions: Pts with R/M HNSCC who progressed on ICI experience longer PFS with the addition of cetuximab to weekly chemotherapy. Further investigation in a larger cohort of pts is needed to fully assess the impact on survival for this treatment combination.

The biology of combination immunotherapy in recurrent metastatic head and neck cancer.

Preclinical data suggest that head and neck cancer is an intrinsically immunosuppressive disease with abnormal inflammatory components in the tumor microenvironment. The development of immune checkpoint inhibitors, which are monoclonal antibodies capable of inhibiting immune suppressive signals to prime anticancer immunity, has revolutionized the therapeutic landscape in recurrent/metastatic head and neck cancer. However, patients with head and neck cancer present primary resistance to immunotherapy. Many ongoing trials include combinations of immunotherapy with different therapeutic interventions, aiming to improve response rates and overall survival. As novel therapy strategies are leveraged, the significance of immunotherapy in recurrent/metastatic head and neck cancer continues to be revealed. This review aims to summarize combinational immunotherapy in head and neck cancer.

Real-World Experience of Immunotherapy from India in Recurrent Squamous Cell Carcinoma of Head and Neck Cancer.

Background Recurrent metastatic head and neck squamous cell carcinoma (HNSCC) patients carry a poor prognosis and have limited therapeutic options. In the randomized phase-3 trial CheckMate 141, nivolumab showed benefit in overall survival (OS) with manageable toxicity. Nivolumab is available for clinical practice since 2017 in India. The aim of this study is to evaluate the efficacy and safety of nivolumab in real-world settings in India. Materials and Methods This is a retrospective, single-center study on the use of nivolumab with advanced or metastatic HNSCC in India. Eligible patients had histologically confirmed, recurrent squamous cell carcinoma of the head and neck (including metastatic disease) of the oral cavity, pharynx, or larynx that was not amenable to curative treatment, tumor progression, or recurrence after the administration of platinum-containing chemotherapy administered as adjuvant therapy or in the context of primary or recurrent disease. We assessed demographics, safety (the Common Terminology Criteria for Adverse Events Version 4.0), response evaluation (the Response Evaluation Criteria in Solid Tumors Version 1.1), progression-free survival (PFS), and OS. Results Among patients with platinum-refractory, recurrent HNSCC, and treatment with nivolumab resulted in median PFS of 2 months and median OS of 5 months, which is inferior to what was seen in CheckMate 141. Fifteen of 20 patients (75%) had progressive disease, 3 (15%) showed a partial response, and 2 (10%) had stable disease. Conclusion Nivolumab was well tolerated in our study with fewer toxic effects, and an inferior median survival was reached as compared with CheckMate 141 in platinum refractory, recurrent HNSCC patients treated with nivolumab because 90% of patients in our study received nivolumab as second-line therapy after progression. Our study encourages the use of nivolumab in this population.

Meeting Proceedings of the 2nd Annual Immuno-Oncology Society of India Conference (I-OSICON-2020), Mumbai, India.

Meeting Proceedings of the 2nd Annual Immuno-Oncology Society of India Conference (I-OSICON-2020), Mumbai, India.

953P Sarcopenia as predictive factor of response to nivolumab in recurrent-metastatic head and neck (RM-SCCHN) cancer patients

Sarcopenia is an emerging problem in cancer patients (pts), significantly higher in SCCHN pts. Aim of this study is to analyze the impact of sarcopenia on efficacy of Nivolumab in RM-SCCHN cancer pts after platinum failure. We retrospectively reviewed clinical and radiological data of 24 RM-SCCHN pts undergoing Nivolumab at Modena University Hospital from 2016 to 2019. Sarcopenia was assessed using abdominal computed tomography scan (CT) before Nivolumab starting and after 8-12 weeks of therapy. Skeletal Muscle Mass (SMI cm2/m2) at L3 levels, Subcutaneous Fat Index (SFI cm2/m2), Visceral Fat Index (VFI cm2/m2) were considered for the analysis; variables were correlated with survival (short vs long survivors, SS vs LS, considering mOS <6month vs ≥ 6mo) and disease control (responders, R, considered as OR + SD vs non-responders, nR). In a subgroup of pts, we described the variation of SMI between the first and the second CT and correlate it with survival and response. 20 pts were evaluable for analysis: 15 (75%) were male; median age: 61 y-o (52-77), most of them had oropharynx (7, 35%) or oral cavity cancers (5, 25%) as primary sites; 13 pts (65%) had a normal BMI before starting Nivolumab. Median OS was 3 mo (0-11): 13 pts (65%) were SS, 7 (35%) LS; R vs nR were 13 (65%) and 7 (35%), respectively. At univariate analysis, no correlation between baseline SMI, SFI, VFI and survival was observed. On the contrary, we found a correlation between mean baseline values of SMI, SFI, VFI and response, in particular for SMI 55,4 in R vs 42,82 in nR, p=0,0008; SFI 61,79 in R vs 38,59 in nR, p=0,0009; for VFI 65,33 in R vs 44,77 in nR, p=0,0431. If we consider 15 pts evaluable for both CTs, 11 pts (73%) had a reduction of SMI at the second CT: mOS was 4 mo (2-9), 7 pts (64%) were SS and 7 pts (64%) were nR. Oppositely, 4 pts (27%) had an increase of SMI: mOS was 10 mo (0-11), 3 pts (75%) were LS and 2 (50%) were R. Sarcopenia is a widespread, but underestimated problem of SCCHN; it may be simply assessed using CT, generally employed for disease evaluation. Detection of body composition and identification of sarcopenia may be a suitable tool to predict response to immunotherapy of SCCHN.

921P Pembrolizumab plus docetaxel for the treatment of recurrent metastatic head and neck cancer: A prospective phase I/II study

921P Pembrolizumab plus docetaxel for the treatment of recurrent metastatic head and neck cancer: A prospective phase I/II study

Evolving Role of Immunotherapy in Recurrent Metastatic Head and Neck Cancer.

Immunotherapy has revolutionized cancer treatment in the past 2 decades, mostly with immune checkpoint blockade approaches. In squamous cell carcinoma of the head and neck (SCCHN), the initial efficacy of immunotherapy was observed in patients with recurrent or metastatic (R/M) disease who received other prior systemic treatment. As monotherapy, anti-PD-1 therapies induce responses in 13% to 18% of patients. More recently, immunotherapy in combination with cytotoxic chemotherapy demonstrated greater safety and efficacy as first-line systemic treatment compared with chemotherapy alone. In R/M SCCHN, the most important benefit of immunotherapy is the significantly improved overall survival, especially in patients with PD-L1-positive tumors. As of 2019, immunotherapy can be used as first-line or subsequent treatment of R/M SCCHN. Many ongoing trials are evaluating immunotherapy combinations or novel immunotherapy strategies, aiming to improve response rate and overall survival. As new targets are identified and new approaches are leveraged, the role of immunotherapy in R/M SCCHN continues to evolve.

Neck dissection prolongs survival in patient with stage IVC hypopharyngeal carcinoma with mixed responses to nivolumab

Surgical intervention aids in maintaining quality of life in patients with recurrent metastatic head and neck carcinoma with mixed responses to nivolumab treatment. However, the mechanisms involved in these mixed responses remain unclear. Systemic chemotherapy using the EXTREME regimen was administered to the patient with hypopharyngeal carcinoma and liver metastases as well as cervical lymph node metastases. The patient was subsequently treated with nivolumab after developing signs of progressive disease. Although the hypopharyngeal tumors and liver metastases were well-controlled, cervical lymph node dissection was performed because of the enlargement of some of the lymph node metastases. Postoperative nivolumab administration was resumed, and this patient is presently alive and disease-free. Immediately after neck dissection, the LNs that responded and those that did not respond to nivolumab were separated and evaluated. The LNs that responded well to nivolumab presented with prominent interstitial fibrosis. Conversely, in LNs that enlarged after nivolumab, significant proliferation of the viable tumor cells and almost no degeneration or necrosis was observed. Additionally, we performed immunohistological assessments on pathologic samples of multiple lesions with differing responses to treatment. Targeted surgical intervention appears to be a valuable adjunct to treatment with nivolumab.

Immunotherapy for Head and Neck Cancer in the Era of Exponentially Increasing Health Care Expenditure.

The FDA-approved immune checkpoint inhibitors, nivolumab and pembrolizumab, are the most recent biological therapies in the therapeutic armamentarium for recurrent metastatic head and neck squamous cell carcinomas. This article highlights the tools for analyzing the costeffectiveness of such therapies.

Cost-Effectiveness of Nivolumab in Recurrent Metastatic Head and Neck Squamous Cell Carcinoma

Treatment options for patients with platinum-refractory, recurrent, metastatic head and neck squamous cell carcinoma (r/m HNSCC) are limited and prognosis is poor. The recent CheckMate 141 clinical trial demonstrated that nivolumab, an anti-programmed cell death protein 1 monoclonal antibody, was efficacious in extending the median overall survival (OS) in this patient population compared with standard therapies. We conducted a cost-effectiveness analysis to determine whether nivolumab is a cost-effective treatment in this patient population and examined various subgroups to determine for which, if any, the treatment is more cost-effective. We implemented a state transition model for HNSCC with a patient cohort who had tumor progression 6 months after the last dose of platinum-containing chemotherapy and compared the cost-effectiveness of nivolumab with docetaxel. Treatment effect estimates and adverse event rates were obtained from CheckMate 141. Costs, utilities, and other model inputs were gathered from published sources. We used a Canadian perspective, a 5-year time horizon, and a 1.5% discount rate for the analysis. Nivolumab extended mean OS by 4 months compared with docetaxel and resulted in fewer treatment-related adverse events, producing an incremental effectiveness of 0.13 quality-adjusted life years (QALY). The incremental cost of treatment with nivolumab was $18,823. At a willingness-to-pay threshold of $100,000/QALY, nivolumab was not a cost-effective treatment option for r/m HNSCC, with an incremental cost-effectiveness ratio of $144,744/QALY. Nivolumab would be cost-effective if its price was reduced by 20%. Our subgroup analysis seemed to indicate that nivolumab might be cost-effective for tumors with expression of programmed death-ligand 1 >5%. We conclude that although nivolumab offers clinical benefit for the treatment of r/m HNSCC over current regimens, it is not cost-effective based on its list price. We have also established a value-based price estimate for nivolumab to be cost-effective in this patient population. Further study is required to draw a definitive conclusion on biomarkers for cost-effectiveness. In health care settings in which cost considerations are a constraint on choice of therapy, patient selection should be carefully considered to maintain efficiency in the system. Until a biomarker for response to therapy is identified for nivolumab, this medication is unlikely to be cost-effective for most patients with recurrent, metastatic head and neck squamous cell carcinoma.