scholarly journals Update of Immune Therapies in Recurrent/Metastatic Head and Neck Cancer

2021 ◽  
pp. 297-306
Author(s):  
Danny Rischin
Keyword(s):  
Overall Survival ◽  
Head And Neck ◽  
Standard Of Care ◽  
First Line ◽  
Immune Therapies ◽  
Positive Score ◽  
Previously Treated ◽  
Combined Positive Score ◽  
Overall Survival Benefit

AbstractSince the initial reports of activity of pembrolizumab in recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC), investigation of the role of immune therapies has been the major focus of clinical trials in R/M HNSCC. Randomised trials initially with nivolumab and later with pembrolizumab established overall survival benefit in patients with R/M HNSCC previously treated with platinum compared to physicians choice of 2nd line therapy, and have led to regulatory approval around the world. More recently the Keynote-048 trial has compared both pembrolizumab monotherapy and pembrolizumab + platinum/5FU to the Extreme regimen of platinum/5FU/cetuximab in the first-line R/M setting. The key findings from this trial are that pembrolizumab monotherapy compared to Extreme improved overall survival in patients with PD-L1 combined positive score (CPS) ≥ 20 and ≥ 1, and that pembro/chemotherapy improved OS in CPS ≥ 20, CPS ≥ 1 and the total population. Relative to Extreme there was less toxicity in the monotherapy arm and comparable toxicity in the pembro/chemo arm. Based on this trial use of pembrolizumab as part of first-line treatment for R/M HNSCC is appropriate for the majority of patients, and represents a new standard of care. The focus has now moved to identifying combinations that may be superior to pembrolizumab monotherapy or to chemotherapy + pembrolizumab. Some of the more promising approaches under investigation in HNSCC are discussed in this chapter. In summary, immune therapies are now the cornerstone of management of R/M HNSCC with the approval of pembrolizumab in the first-line R/M setting.

scholarly journals Optimizing Treatment for Head and Neck Cancers: Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma

2020 ◽  
Vol 18 (7.5) ◽  
pp. 982-984
Author(s):  
Robert I. Haddad
Keyword(s):  
Head And Neck ◽  
Single Agent ◽  
Standard Of Care ◽  
Phase Iii ◽  
Routine Practice ◽  
Second Line ◽  
First Line ◽  
Positive Score ◽  
Combined Positive Score ◽  
Line Setting

Immunotherapy has changed the game in the treatment of head and neck cancer (HNC). Practice-changing results from the phase III KEYNOTE-048 trial led to the approval of pembrolizumab immunotherapy alone or in combination with chemotherapy for the treatment of recurrent/metastatic HNC in the first-line setting. Testing for combined positive score (CPS) is now part of routine practice, because patients with CPS ≥1 can be started on single-agent immunotherapy in the first-line. Pembrolizumab replaces the “old” standard of care established by the EXTREME study, as trials looking at targets besides immunotherapy have proved “disappointing.” Additionally, nivolumab and pembrolizumab are both approved for use in the second-line.

scholarly journals Evolving Role of Immunotherapy in Recurrent Metastatic Head and Neck Cancer

2020 ◽  
Vol 18 (7) ◽  
pp. 899-906 ◽  
Author(s):  
Xiuning Le ◽  
Renata Ferrarotto ◽  
Trisha Wise-Draper ◽  
Maura Gillison
Keyword(s):  
Overall Survival ◽  
Head And Neck ◽  
Systemic Treatment ◽  
Immune Checkpoint Blockade ◽  
Subsequent Treatment ◽  
First Line ◽  
Improve Response Rate ◽  
The Past ◽  
Important Benefit

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.

scholarly journals Association of programmed death ligand 1 expression with prognosis among patients with ten uncommon advanced cancers

2020 ◽  
Vol 6 (8) ◽  
pp. FSO616
Author(s):  
Torben Steiniche ◽  
Morten Ladekarl ◽  
Jeanette Bæhr Georgsen ◽  
Simon Andreasen ◽  
Michael Busch-Sørensen ◽  
...  
Keyword(s):  
Overall Survival ◽  
Prognostic Value ◽  
Median Overall Survival ◽  
Checkpoint Inhibitors ◽  
First Line ◽  
Programmed Death Ligand 1 ◽  
Programmed Death ◽  
Positive Score ◽  
Combined Positive Score ◽  
First Line Treatment

Aim: PD-L1 expression and high levels of microsatellite instability (MSI-H) may predict response to checkpoint inhibitors, but their prevalence and prognostic value are unknown in many cancers. Methods: We retrospectively evaluated PD-L1 combined positive score (CPS) and MSI-H and their association with clinical outcomes among patients with ten advanced uncommon cancers. Results: 398 of 426 patients (93%) had a valid PD-L1 result; most (242; 61%) had CPS ≥1. Prevalence of MSI-H tumors was 8/360. Median overall survival was shorter among patients with PD-L1 CPS ≥1 tumors after first-line treatment (23.0 vs 39.7 months, p = 0.014). Conclusion: PD-L1 was commonly expressed in solid tumors, and CPS ≥1 was associated with shorter overall survival. Prevalence of MSI-H was low.

282 Pan-tumor analysis of the association between PD-L1 combined positive score and response to pembrolizumab monotherapy

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A308-A308
Author(s):  
Lingkang Huang ◽  
Jared Lunceford ◽  
Junshui Ma ◽  
Kenneth Emancipator
Keyword(s):  
Tumor Cells ◽  
Immune Cells ◽  
Roc Analysis ◽  
Standard Of Care ◽  
Tumor Type ◽  
Operating Characteristics ◽  
Positive Score ◽  
Combined Positive Score ◽  
Line Of Therapy ◽  
Tumor Types

BackgroundPD-L1 is expressed on both tumor and immune cells; however, the mechanism by which PD-L1 modulates the adaptive immune response on tumor versus immune cells may differ. Additionally, the prevalence of PD-L1 expression and the partitioning between tumor and immune compartments varies by tumor type. While PD-L1 expression on tumor or immune cells can be scored separately, the PD-L1 combined positive score (CPS) captures both tumor and immune cell expression in one aggregate score. We performed a retrospective, exploratory analysis of the effectiveness of CPS as an enrichment biomarker across several studies of pembrolizumab monotherapy in patients with multiple tumor types.MethodsPD-L1 expression was assessed using PD-L1 IHC 22C3 pharmDx. Expression was measured using CPS (defined as the number of PD-L1–staining cells [tumor cells, lymphocytes, macrophages] divided by the total number of tumor cells, multiplied by 100) in tumor samples from single-arm (KEYNOTE-052 [UC], KEYNOTE-059 cohort 1 [G/GEJ], KEYNOTE-086 [TNBC], KEYNOTE-158 [cervical; SCLC], KEYNOTE-180 [EC], KEYNOTE-224 [HCC], KEYNOTE-427 [RCC]) and randomized (KEYNOTE-040 [HNSCC], KEYNOTE-045 [UC], KEYNOTE-061 [G/GEJ], KEYNOTE-119 [TNBC], KEYNOTE-240 [HCC]) pembrolizumab studies. Data were pooled across tumor types for pembrolizumab and for standard-of-care (in controlled studies), and then estimates of response rate, prevalence, and receiver operating characteristics (ROC) analysis were performed over various CPS cutpoints. CPS distribution by response, tumor type, and line of therapy were also assessed.ResultsThere were 3769 treated patients with available PD-L1 CPS (pembrolizumab, n=2678; standard-of-care, n=1091). The area under the ROC curve for ORR was 0.63 (95% CI, 0.61–0.66) for pembrolizumab and 0.48 (95% CI, 0.43–0.53) for standard-of-care when a positive association was evaluated between CPS and ORR (figure 1); individual cutpoints of 1, 10, 20, and 50 were examined (table 1). Figure 2 shows a boxplot of CPS distribution for response in pembrolizumab-treated patients.Abstract 282 Table 1Response Rates and Sensitivity at Individual CPS Cutpoints for Pembrolizumab-Treated PatientsAbstract 282 Figure 1ROC analysis of PD-L1 CPS for pembrolizumab versus standard-of-care therapyAbstract 282 Figure 2Boxplot of PD-L1 CPS distribution for responders versus nonresponders in pembrolizumab-treated patients by tumor type and line of therapy in order of descending median CPSConclusionsThis retrospective, exploratory pan-tumor analysis demonstrates that CPS is an effective scoring method for measuring PD-L1 expression and can be used as a predictive biomarker to identify patients likely to respond to pembrolizumab monotherapy. CPS demonstrated enrichment of response to pembrolizumab monotherapy across most, but not all, tumor types, including some tumor types for which efficacy favors pembrolizumab regardless of PD-L1 expression, and for which a companion diagnostic is therefore not needed. In the randomized studies, CPS did not show a consistent association with ORR for standard-of-care therapy.

scholarly journals Circulating MicroRNAs as Prognostic Molecular Biomarkers in Human Head and Neck Cancer: A Systematic Review and Meta-Analysis

2019 ◽  
Vol 2019 ◽  
pp. 1-12 ◽  
Author(s):  
Shree Ram Lamichhane ◽  
Thanuja Thachil ◽  
Harriet Gee ◽  
Natalie Milic
Keyword(s):  
Systematic Review ◽  
Overall Survival ◽  
Head And Neck Cancer ◽  
Head And Neck ◽  
Cancer Patients ◽  
Neck Cancer ◽  
Meta Analysis ◽  
Prognostic Role ◽  
Circulating Micrornas

Background. Circulating microRNAs (miRNAs) are potential molecular biomarkers for cancer detection; however, little is known about their prognostic role in head and neck cancer. This current study is aimed at evaluating the role of novel miRNAs in the survival of head and neck cancer patients. Materials and Methods. We performed a systematic literature search using online databases for articles published between December 2006 and February 2019. A meta-analysis was conducted to assess the correlation between miRNA expressions and overall survival (OS) among the selected head and neck cancer studies. After multilevel screening by reviewers, meta-analysis was performed using hazard ratios (HR) and associated 95% confidence interval (CI) of survival to calculate a pooled effect size. Result. A total of 1577 patients across 13 studies were included in the literature review, with 18 miRNAs upregulated and 4 miRNAs downregulated predicting a poor overall survival. The forest plot generated using cumulated survival data resulted in a pooled HR value of 2.943 (95% CI: 2.394-3.618) indicating a strong association of dysregulated miRNA expression with a poor outcome. Only 2 miRNAs—low levels of miR-9 and high levels of miR-483-5p—were observed in two studies, both showing a significant association with overall cancer survival. Conclusion. To our knowledge, this is the first comprehensive systematic review and meta-analysis that examines the prognostic role of circulating miRNAs from blood in head and neck cancer patients. The combined effect estimates a HR across multiple studies and also supports the previous individual findings that an alteration in miRNA expression is highly associated with poor prognosis. This has the potential to use serum and/or plasma miRNAs as biomarkers and become novel tools for predicting the prognosis of head and neck cancer patients in the near future.

ENGOT-en9/LEAP-001: A phase III study of first-line pembrolizumab plus lenvatinib versus chemotherapy in advanced or recurrent endometrial cancer.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. TPS6106-TPS6106
Author(s):  
Christian Marth ◽  
Christof Vulsteke ◽  
Maria Jesus Rubio Pérez ◽  
Vicky Makker ◽  
Elena Ioana Braicu ◽  
...  
Keyword(s):  
Overall Survival ◽  
Endometrial Cancer ◽  
Objective Response ◽  
Phase Iii ◽  
Primary Study ◽  
Antiangiogenic Agents ◽  
Newly Diagnosed ◽  
First Line ◽  
Phase Iii Study ◽  
Previously Treated

TPS6106 Background: The prognosis for endometrial cancer (EC) can be favorable when diagnosed in early stages, but prognosis and overall survival are poor in patients with advanced or recurrent EC. First-line standard of care for patients with advanced or recurrent EC is paclitaxel and carboplatin chemotherapy; however, there is a need for more effective and tolerable therapies. In the phase Ib/II trial KEYNOTE-146, which assessed the PD-1 inhibitor pembrolizumab (pembro) in combination with the multikinase inhibitor lenvatinib, an objective response rate (ORR) of 38% was observed (N=108) in patients with previously treated advanced EC. ENGOT-en9/LEAP-001 (NCT03884101) is a randomized, open-label, active-controlled, phase III study investigating pembro + lenvatinib vs chemotherapy in patients with newly diagnosed advanced or recurrent EC. Methods: Patients with newly diagnosed advanced (stage III-IV) or recurrent EC not previously treated with antiangiogenic agents; systemic chemotherapy (unless within a chemoradiation regimen); PD-1, PD-L1, or PD-L2 inhibitors; or other T-cell receptor–targeted therapies will be eligible. Patients will be randomized 1:1 to receive pembro 200 mg every 3 wk (Q3W) + lenvatinib 20 mg daily or paclitaxel 175 mg/m2 Q3W + carboplatin AUC 6 Q3W. Randomization will be stratified on the basis of proficient vs deficient mismatch repair (pMMR vs dMMR) status. The pMMR population will be further stratified by prior chemoradiation (yes vs no), measurable disease (yes vs no), and ECOG performance status (0 vs. 1). Patients will continue on treatment for up to 35 cycles of pembro vs 7 cycles of chemotherapy or until initiation of a new anticancer treatment, unacceptable adverse events, or withdrawal of consent. Primary study endpoints are progression-free survival (per RECIST v1.1 by blinded independent central review) and overall survival. Secondary study endpoints are ORR, health-related quality of life, safety and tolerability, and lenvatinib pharmacokinetics. Exploratory endpoints will include disease control rate, clinical benefit rate, and duration of response. Enrollment is ongoing. Clinical trial information: NCT03884101.

scholarly journals Update on Systemic Therapy for Advanced Soft-Tissue Sarcoma

2020 ◽  
Vol 27 (11) ◽  
pp. 25-33 ◽  
Author(s):  
A. Smrke ◽  
Y. Wang ◽  
C. Simmons
Keyword(s):  
Overall Survival ◽  
Clinical Trials ◽  
Soft Tissue ◽  
Soft Tissue Sarcoma ◽  
Systemic Therapy ◽  
English Language ◽  
Standard Of Care ◽  
Current Evidence ◽  
First Line ◽  
First Line Therapy

Background: Soft-tissue sarcoma (sts) represents a rare group of mesenchymal neoplasms comprising more than 50 heterogeneous subtypes. Great efforts have been made to increase the understanding of the treatment of advanced sts (unresectable or metastatic disease). We set out to determine whether outcomes for patients with advanced sts have improved over time and to assess the current evidence for systemic therapy. Methods: In a scoping review, we evaluated the contemporary evidence for systemic treatment of advanced sts in adults (>18 years of age). Phase i, ii, and iii studies of systemic therapy for advanced sts published in the English language were included. After abstract and full-text review of seventy-seven studies, sixty-two trials met the inclusion criteria. Results: The number of clinical trials conducted and published in advanced sts has increased over the last 30 years. Although median overall survival has increased, attempts at improving first-line therapy through dose intensification, doublet chemotherapy, or alternative backbones have not been successful. The optimal therapy beyond anthracyclines remains a challenge, especially given the heterogeneity that grouping multiple sts subtypes within clinical trials creates. However, increasing numbers of agents are being studied, and several studies had shown isolated benefit in progression-free or overall survival. Summary: First-line systemic therapy with an anthracycline remains the standard of care for advanced sts. However, choice of subsequent therapy beyond anthracyclines remains challenging. Novel systemic therapies, use of molecular diagnostics to direct therapy, subtype-specific trials, and learnings from real-world retrospective data are all important for improving outcomes in patients with advanced sts.

scholarly journals Single Centre Experience of Managing Patients with Double Hit Lymphoma

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 5868-5868
Author(s):  
Shankaranarayana Paneesha ◽  
Iman Qureshi ◽  
Malahat Saeed ◽  
Richard Lovell ◽  
Emmanouil Nikolousis ◽  
...  
Keyword(s):  
Overall Survival ◽  
Complete Remission ◽  
Progressive Disease ◽  
Salvage Chemotherapy ◽  
Line Treatment ◽  
First Line ◽  
Single Centre ◽  
Single Centre Experience ◽  
First Line Treatment

Abstract Double or triple hit Lymphomas (DHL) are characterized by translocation rearrangements of C-MYC with the addition of BCL2 and/or BCL 6, which are associated with a poor outcome due to their genetic complexity . Clinical controversies remain regarding the optimum treatment for patients with DHL due to lack of consensus regarding the optimal management and also age and frailty being a significant obstacle, limiting the role of dose-escalated or intensified therapy. Literature review suggests overall median survival for DHL patients is from 0.2-1.5years2. We report our single centre experience of treating this patient group. Materials & Methods: This single centre retrospective study evaluated the outcome of DHL patients who underwent various lines of treatment including standard R-CHOP chemotherapy, more intensive chemotherapy regimens and allogeneic stem cell transplantation (AlloSCT). Diagnosis of DHL was as per the 2008 WHO classification. Statistical analysis was performed by using SPSS 23®. Results: Our study included fourteen patients (9M; 5F) with a median age 60.5 years (range 33-65). 4 patients had stage 2B disease, 3 had stage 3B and 7 had 4B disease. R-CHOP chemotherapy only was commenced as first line treatment in 4 patients, R-CHOP plus intrathecal chemotherapy was given to 2 patients and 1 patient received R-CEOP. 5 patients received intensive chemotherapy with R-CODOX-M/R-IVAC where as one patient received EPOCH in a different centre prior to transfer. 1 patient received radiotherapy only. 10 patients were in complete remission following first line chemotherapy. One patient progressed following first line treatment and was managed palliatively. One patient relapsed whilst awaiting AlloSCT and was given mini-DEX BEAM salvage chemotherapy prior to transplant. One patient had a partial response to first line treatment and was given further rituximab but had progressive disease and was also managed palliatively. One patient had progressive disease and received GDP chemotherapy. 8 patients underwent AlloSCT with BEAM Alemtuzumab conditioning with cyclosporine as GvHD prophylaxis (6 unrelated and 2 sibling donors). The mean overall survival from starting treatment for DHL for the non-transplant cohort was 18.5 months (Range: 0.5 to 36.5) and the median OS was 8.3 months (Range: 4 to 12.6) as compared to mean overall survival of 44.2 months (Range: 22.2 to 66.35) in the transplant cohort with median overall survival not reached (p value: 0.46, Log Rank). In our patients, there was no progression after 3 months from Allo SCT. One patient progressed 6 weeks and died 8 weeks post AlloSCT, whereas two patients progressed 12 weeks and died 14 weeks post AlloSCT. In the cohort who did not undergo AlloSCT, 3 patients have died and two remain in complete remission and 1 patient is undergoing salvage chemotherapy for refractory disease. Conclusion: Our single centre experience of limited number of patients with DHL suggests AlloSCT as a consolidative treatment in first complete remission, may offer survival benefit as compared to no consolidation. Our data also shows no progression of DHL 3 months post AlloSCT highlighting the potential graft versus lymphoma effect. This requires further evaluation in a larger cohort to confirm our preliminary findings and identify potential biomarkers of best response. Confirmation of this result in larger cohort will identify the role of AlloSCT in DHL and enable to reach consensus in the DHL management. Disclosures Kishore: celgene: Other: travel grant.

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