A retrospective analysis of treatment patterns, overall survival, and real-world disease-free survival in early-stage non-small cell lung cancer following complete resection.

BACKGROUND: Real-world data regarding patient characteristics, adjuvant treatment patterns, and long-term survival outcomes are needed to better understand unmet needs among patients with completely resected early-stage non-small cell lung cancer (NSCLC). METHODS: Electronic medical records from the U.S.-based ConcertAI Patient360™ database were analyzed in patients with stage IB-IIIA NSCLC who underwent complete resection prior to March 1, 2016. Patients were followed until death or July 1, 2021. This study evaluated adjuvant chemotherapy use, and overall survival (OS) and real-world disease-free survival (rwDFS) outcomes using the Kaplan-Meier method. The correlation between OS and rwDFS was assessed using the Kendall rank test. Among patients who did not recur 5 years following surgery, landmark analyses of OS and rwDFS were conducted to understand the subsequent survival impact of remaining disease-free for at least 5 years. RESULTS: Data from 441 patients with completely resected stage IB-IIIA NSCLC were included. About 35% of patients received adjuvant chemotherapy post-resection. Median OS and rwDFS from resection were 83.1 months and 42.4 months, respectively. The 5-year OS and rwDFS rates were 65.7% and 42.1%, respectively. OS and rwDFS were positively correlated (Kendall rank correlation coefficient = 0.67; p < 0.0001). Among patients without recurrence within 5 years after resection, the subsequent 5-year OS and rwDFS survival rates were 52.9% and 36.6%, respectively. CONCLUSIONS: Use of adjuvant chemotherapy was low, and the overall 5-year OS rate remained low despite all patients having undergone complete resection. Patients who remained non-recurrent over time had favorable subsequent long-term survival.

Clinical and economic impact of recurrence in early-stage non-small-cell lung cancer following complete resection.

Aim: Real-world data on outcomes for early-stage non-small-cell lung cancer (NSCLC) are needed to better understand the benefits of new therapies. Methods: In this retrospective study using the ConcertAI Patient360™ database, overall survival and healthcare resource utilization were compared among patients with recurrent and non-recurrent completely resected stage IB-IIIA NSCLC. Results: Recurrence was associated with a shorter median overall survival compared with non-recurrence (31.5 months vs 75.6 months, respectively), lower survival probability 5-years post-resection, and higher healthcare resource utilization. Patients with late recurrence had a longer restricted mean survival time versus patients with early recurrence. Conclusion: Results from this real-world study highlight the potential value of preventing or delaying recurrence in patients with early-stage NSCLC.

This study looked at how people with early-stage non-small-cell lung cancer did after surgery to completely remove the disease. It compared two groups of patients: those whose disease came back after surgery and those whose disease did not come back after surgery. The group of people whose disease came back after surgery did not live as long as those whose disease did not come back after surgery (31.5 months vs 75.6 months). Patients whose disease came back had a lower chance of living at least 5 years after surgery and they had more hospital visits and doctor's office visits. In addition, those whose disease came back within 1 year did not live as long as those whose disease came back between 1 and 5 years after surgery. Preventing or delaying the return of disease after surgery is important for improving the lives of patients with early-stage non-small-cell lung cancer.

Real-world outcomes of systemic therapy in locally advanced, recurrent or metastatic cutaneous squamous cell carcinoma.

Aim: Real-world treatment patterns and clinical outcomes in advanced cutaneous squamous cell carcinoma were evaluated. Methods: Adults receiving their first systemic therapy for unresectable, locally advanced or recurrent/metastatic cutaneous squamous cell carcinoma from 4 September 2014 to 30 June 2017, were evaluated. The primary end point was real-world overall response rate per Response Evaluation Criteria in Solid Tumors or physician assessment. Time-to-event outcomes were assessed using the Kaplan-Meier method. Results: Of 51 eligible patients, the median age was 76 years, 80% were male and 65% had an Eastern Cooperative Oncology Group score of 0-1. The most common regimens were cetuximab (51%) and carboplatin + paclitaxel (22%). Median real-world overall response rate ranged from 9.8% per Response Evaluation Criteria in Solid Tumors to 43.1% when supplemented by physician assessment. Median overall survival was 10.7 months, and median time to next treatment was 7.5 months. Conclusion: Survival in advanced cutaneous squamous cell carcinoma was short. Real-world overall response rate was lower with Response Evaluation Criteria in Solid Tumors than physician assessment.

This study looked at chemotherapy treatments and responses in patients receiving treatment for advanced cutaneous squamous cell carcinoma, a type of skin cancer. Patients had advanced and metastatic cancer that could not be cured by radiation or surgery. Most of the patients were white males, and their median age was 76 years. About two-thirds of the patients in the study had their original cancer in the head and neck, and in most patients (approximately 80%), the cancer had spread, mostly to the lungs or lymph nodes. Half of the patients in the study were treated with cetuximab, and about a quarter received platinum chemotherapy or other cetuximab-based treatment. The study examined how response to treatment may be measured in clinical care and clinical trials. Response to treatment and length of survival were short: patients responded to treatment for a median of 9 months and survived for a median of 10.7 months.

Real-world time on treatment with immuno-oncology therapy in recurrent/metastatic head and neck squamous cell carcinoma.

Aim: We report real-world time on treatment (rwToT) with immuno-oncology (I-O) and other systemic therapies in second-line recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC) previously treated with platinum therapies. Materials & methods: Adult patients receiving first-line platinum therapy for R/M HNSCC between January 2017 and December 2018 and a second-line therapy were selected from a US electronic medical record database. Results: In our study sample of 619 R/M HNSCC patients, second-line treatments primarily included I-O therapies (71%) and resulted in median rwToT of 2.8 months and 12-month on-treatment rate of 19.3%. For other second-line therapies, median rwToT and 12-month on-treatment rate was 1.9 months and 1.3%, respectively. Conclusion: Use of second-line I-O therapies was common and resulted in rwToT consistent with R/M HNSCC clinical trials.

Lay abstract Head and neck cancer include tumors that develops in the mouth, throat, nose, salivary glands, oral cancers or other areas of the head and neck. When this cancer returns or spreads to another part of the body, systemic chemotherapies are often used with the goal of prolonging survival. Immunotherapy has emerged as a new approach to treat head and neck cancer by using the body's own immune system to kill cancer cells. The purpose of this study was to better understand the use of immunotherapies in patients with head and neck cancer after the cancer has returned or spread to another part of the body. The study showed that immunotherapies were commonly used and resulted in fewer treatment discontinuations in comparison to other systemic chemotherapies. These results support the use of immunotherapies in this patient population.

Global longitudinal assessment of treatment outcomes in recurrent/metastatic nasopharyngeal carcinoma: GLANCE-NPC study.

Aim: Given a lack of standard of care treatment for recurrent/metastatic nasopharyngeal carcinoma (R/M NPC), we assessed treatment patterns and overall survival in the real-world setting. Materials & methods: A retrospective chart review was conducted in patients who initiated first-line systemic therapy in Taiwan and South Korea between January 2012 and June 2013 with follow-up through December 2015. Results: Among 154 R/M NPC patients, all patients in Taiwan (n = 104) had distant metastases, whereas in South Korea (n = 50) 42% had distant metastases. Patients with distant metastases generally received systemic therapy only (71%) for whom median overall survival was 23 months (95% CI: 18-32). Conclusion: Prognosis in R/M NPC with distant metastases remains poor, underscoring the need for more efficacious treatments.

Lay abstract Nasopharyngeal carcinoma is an invasive cancer affecting the area behind the nose and above the back of throat. When this cancer returns or spreads to another part of the body, patients receive chemotherapy options with the goal of prolonging survival. To understand chemotherapy approaches used in everyday practice and their effectiveness, we conducted a review of medical records in Taiwan and South Korea. We studied 154 patients who started a first chemotherapy between January 2012 and June 2013 and followed patients through December 2015. Patients whose cancer spread in another part of their body generally received chemotherapy without radiation and lived 23 months on average. Our findings show that more effective treatments must be developed to help prolong survival.

Treatment patterns and outcomes among patients with recurrent/metastatic squamous cell carcinoma of the head and neck.

AIM: Cetuximab was approved in 2008 for treating recurrent/metastatic (R/M) head-and-neck squamous-cell carcinoma (HNSCC), and this study assessed the utilization of cetuximab for R/M-HNSCC in a real-world setting. MATERIALS & METHODS: Adult patients with R/M-HNSCC, who initiated systemic therapy between 1 September 2011 and 31 December 2014 and followed through 31 December 2015, were identified from iKnowMed electronic-health-records database (McKesson Specialty Health) supplemented with manual chart-abstraction. RESULTS: For 325 R/M-HNSCC patients; median age 62 years; 82% males, 67% had oropharyngeal cancer, most common first-line (1L) regimen was platinum-based combinations (76%), of whom only 8% received platinum + cetuximab +/- 5-fluorouracil. CONCLUSION: Despite US FDA approval and National Comprehensive Cancer Network guidelines recommending use of cetuximab for palliative treatment of R/M-HNSCC, our study demonstrates low utilization in 1L and 2L settings, underscoring the need to understand reasons for low utilization.

5-Year Real-World Outcomes With Frontline Pembrolizumab Monotherapy in PD-L1 Expression ≥ 50% Advanced NSCLC.

BACKGROUND: In clinical trials, frontline pembrolizumab for advanced NSCLC has demonstrated durable, clinically meaningful, long-term survival benefits over chemotherapy. Our objective was to evaluate 5-year survival rates outside the idealized setting of clinical trials for advanced/metastatic NSCLC treated with frontline pembrolizumab monotherapy. METHODS: Using a nationwide, electronic health record-derived, deidentified database in the United States, we studied adult patients with advanced/metastatic NSCLC (unresectable stage IIIB/IIIC, or stage IV), with PD-L1 expression ≥ 50%, no documented EGFR, ALK, or ROS1 genomic alteration, and ECOG performance status of 0-1 initiating frontline pembrolizumab monotherapy from November 1, 2016, through March 31, 2020, excluding those in clinical trials. Kaplan-Meier was used to determine overall survival (OS). Data cutoff was May 31, 2023. RESULTS: A total of 804 patients were eligible for the study, including 404 women (50%); median age was 72 years (range, 38-85 years), with 310 patients (39%) ≥ 75 years old. Median follow-up time from pembrolizumab initiation to data cutoff was 60.5 months (range, 38.0-78.7). At data cutoff, 549 patients (68%) had died. Median OS was 19.2 months (95% CI, 16.6-21.4), and survival rate at 5 years was 25.1% (95% CI, 21.7-28.7). Overall, 266 patients (33%) received 1 or more subsequent regimens, most commonly an anti-PD-(L)1 agent (as monotherapy or combination therapy) or platinum-based chemotherapy. CONCLUSIONS: With 5-year follow-up in a real-world population, frontline pembrolizumab monotherapy continues to demonstrate long-term effectiveness, with survival outcomes consistent with those of pivotal clinical trials, for treating patients with advanced NSCLC with PD-L1 expression of ≥ 50% and no EGFR, ALK, or ROS1 genomic alteration.

Real-world outcomes on platinum-containing chemotherapy for EGFR-mutated advanced nonsquamous NSCLC with prior exposure to EGFR tyrosine kinase inhibitors.

Background: Front-line therapy with an EGFR tyrosine kinase inhibitor (TKI) is the standard of care for treating patients with advanced nonsquamous NSCLC with the common sensitizing EGFR exon 19 deletion and exon 21 L858R point mutations. However, EGFR TKI resistance inevitably develops. The optimal subsequent therapy remains to be identified, although platinum-containing chemotherapy regimens are often administered. Our objectives were to describe baseline characteristics, survival, and subsequent treatment patterns for patients with advanced nonsquamous NSCLC with EGFR exon 19 deletion or L858R mutation who received a platinum-based combination regimen after front-line EGFR TKI therapy. Methods: This retrospective study used a nationwide electronic health record-derived deidentified database to select adult patients with advanced nonsquamous NSCLC, evidence of EGFR exon 19 deletion or L858R mutation, and ECOG performance status of 0-2 who initiated platinum-containing chemotherapy, with or without concomitant immunotherapy, from 1-January-2011 to 30-June-2020 following receipt of any EGFR TKI as first-line therapy or, alternatively, a first- or second-generation EGFR TKI (erlotinib, afatinib, gefitinib, dacomitinib) as first-line therapy followed by the third-generation EGFR TKI osimertinib as second-line therapy. Data cut-off was 30-June-2022. The Kaplan-Meier method was used to estimate overall survival (OS) after initiation of pemetrexed-platinum (n=119) or any platinum-based combination regimen (platinum cohort; n=311). Results: The two cohorts included two-thirds women (65%-66%) and 57%-58% nonsmokers; median ages were 66 and 65 years in pemetrexed-platinum and platinum cohorts, respectively. Median OS was 10.3 months (95% CI, 8.1-13.9) from pemetrexed-platinum initiation and 12.4 months (95% CI, 10.2-15.2) from platinum initiation; 12-month survival rates were 48% and 51%, respectively; 260 patients (84%) had died by the end of the study. Conclusion: The suboptimal survival outcomes recorded in this study demonstrate the unmet need to identify more effective subsequent treatment regimens for patients with EGFR-mutated advanced nonsquamous NSCLC after EGFR TKI resistance develops.

Real-World Neoadjuvant Treatment Patterns and Outcomes in Resected Non-Small-Cell Lung Cancer.

BACKGROUND: Novel neoadjuvant chemoimmunotherapy treatments are being investigated for locally advanced non-small-cell lung cancer (NSCLC), but real-world outcomes for neoadjuvant treatments are poorly understood. This study examined neoadjuvant treatment patterns, real-world event-free survival (rwEFS) and overall survival (OS) in patients with resected, stage II-III NSCLC in the United States (US). METHODS: This retrospective study identified patients in the SEER-Medicare database (2007-2019) with newly diagnosed stage II, IIIA, and IIIB (N2) NSCLC (AJCC 8th edition) treated with neoadjuvant chemo/chemoradiotherapy and resection (index date: neoadjuvant therapy initiation). Neoadjuvant treatment regimens were described. rwEFS (time from index to first recurrence or death, whichever occurred first) and OS (time from index to death) were summarized by Kaplan-Meier analysis for overall population, by disease stage at diagnosis, and by neoadjuvant treatment modality. RESULTS: 221 patients (stage II, N=70; stage III, N=151) met eligibility criteria. The median follow-up from index was 32.7 months. All patients received neoadjuvant chemotherapy (51%) or chemoradiotherapy (49%) prior to surgery; 97% of patients received platinum-based regimens, among which carboplatin+paclitaxel was the most frequent (45%). In all patients, median rwEFS was 17.6 months and 5-year rwEFS was 20.9%; median OS was 48.5 months and 5-year OS was 44.9%. 71% of patients had disease recurrence during follow-up; among them, 28% developed locoregional recurrence as the first recurrence event. CONCLUSIONS: Patients with resected, stage II-III NSCLC who received neoadjuvant chemo/chemoradiotherapy have high rates of disease recurrence and poor survival outcomes, highlighting need for more effective treatments to improve survival rates.

Chronic myeloid leukemia (CML): association of treatment satisfaction, negative medication experience and treatment restrictions with health outcomes, from the patient's perspective.

BACKGROUND: The availability of the tyrosine-kinase inhibitor (TKI), imatinib, and later introduction of second generation TKIs, dasatinib and nilotinib, have not only improved clinical outcomes of patients with chronic myeloid leukemia (CML), but also provide multiple therapeutic options for CML patients. Despite the widespread use of these oral therapies, little is known about the impact of different treatment regimens on patient-reported outcomes (PROs) among CML patients. The objective of this study was to assess the impact of patient-reported treatment restrictions and negative medication experiences (NMEs) on satisfaction and other health outcomes among patients with CML treated with oral TKIs. METHODS: Participants recruited from survey panels and patient networks in the United States (US) and Europe completed an online questionnaire. Respondents included adults (≥ 18 years) with chronic-phase CML currently on TKI treatment. Study variables included treatment difficulty (i.e., difficulty in following treatment regimens), CML dietary/dosing requirements, NMEs, and validated PROs assessing treatment satisfaction, health-related quality of life (HRQoL), activity impairment, and non-adherence. Structural equation models assessed associations among variables, controlling for covariates. RESULTS: 303 patients with CML (US n=152; Europe n=151; mean age 51.5 years; 46.2% male) completed the questionnaire. Approximately 30% of patients reported treatment difficulties; treatment difficulty was higher among nilotinib (63.3%) than among dasatinib (2.6%) or imatinib (19.2%) treated patients (p<0.0001). Non-adherence was generally low; however, patients on nilotinib vs. imatinib reported missing doses more often (p<0.05). Treatment satisfaction was associated with significantly increased HRQoL (p<0.05) and lower activity impairment (p<0.01). NMEs were associated with decreased treatment satisfaction (p<0.01) and HRQoL (p<0.05), and greater activity impairment (p<0.01). Higher overall treatment restrictions were associated with greater treatment difficulty (p<0.001), which correlated with non-adherence (p<0.01). CONCLUSIONS: Treatment satisfaction and NMEs are important factors associated with HRQoL among patients with CML. Increased treatment restrictions and associated difficulty may affect adherence with TKIs. Choosing a CML treatment regimen that is simple and conveniently adaptable in patients' normal routine can be an important determinant of HRQoL and adherence.

Prevalence of mixed dyslipidemia among Australian patients undergoing lipid-modifying therapy.

BACKGROUND: Few studies have assessed the prevalence of mixed dyslipidemia (MD) and the effectiveness of lipid-modifying therapy (LMT) for the treatment of abnormal levels of low-density lipoprotein cholesterol (LDL-C), triglycerides (TG) and high-density lipoprotein cholesterol (HDL-C) in Australian clinical practice. OBJECTIVE: To estimate the prevalence of MD in Australian patients undergoing LMT. METHODS: Patients 35 years of age and older undergoing LMT for ≥1 year were enrolled from nine general practice and cardiologist/endocrinologist outpatient clinics in Australia between April 2007 and May 2008. Lipid levels, including LDL-C, HDL-C and TG levels, were prospectively collected at the enrollment date and from patient records one year before LMT was initiated. Normal lipid levels were assessed according to Australian guidelines. Multivariate logistic regression was used to evaluate predictors of normal lipid level attainment. RESULTS: Of 297 patients (mean age 60.1 years; 43% male), the prevalence of MD before LMT was 61%; 93% of patients had elevated LDL-C levels, 17% had low HDL-C levels and 62% had elevated TG levels. Following LMT (98.3% statins), 31% of patients had MD. The prevalence of elevated LDL-C levels, low HDL-C levels and elevated TG levels were 44%, 21% and 42%, respectively. Baseline lipid levels were significant predictors of attainment of normal LDL-C levels (OR 0.42 [95% CI 0.27 to 0.63]) and TG levels (OR 0.26 [95% CI 0.16 to 0.45]). CONCLUSION: Among Australian patients primarily treated with statins, nearly one-third had MD despite LMT. LMT considerably improved LDL-C goal attainment; however, a large proportion of patients did not achieve normal HDL-C and TG levels. Patients may benefit from a more comprehensive approach to lipid management that treats all three lipid risk factors, as suggested in clinical guidelines.

Treatment Patterns and Outcomes in Resected Early-stage Non-small Cell Lung Cancer: An Analysis of the SEER-Medicare Data.

BACKGROUND: As the non-small cell lung cancer (NSCLC) adjuvant treatment landscape evolves, an evaluation of treatment patterns and outcomes of patients with early-stage, resected NSCLC eligible for adjuvant treatment in routine clinical practice is needed to better understand the unmet needs in this patient population. MATERIALS AND METHODS: Data from the Surveillance, Epidemiology, and End Results (SEER)-Medicare database (2007-2019) were used to identify patients with newly diagnosed stage IB (tumor size ≥4cm)-IIIA (AJCC 7th edition) NSCLC who received primary surgery (index date). We assessed adjuvant treatment patterns, real-world disease-free survival (rwDFS; time from index date to first recurrence or death) and overall survival (OS; time from index date to death), and loco-regional recurrence pattern and treatment distribution. RESULTS: Among 1761 patients with primary surgery, mean age was 73.8 years; 47.9% were male; and 83.9% were white. Approximately 41% of patients received adjuvant chemotherapy; median time from surgery to adjuvant chemotherapy initiation was 48 days, and the most frequently observed adjuvant chemotherapy regimen was carboplatin+paclitaxel (24.5%). In the overall population, median rwDFS was 24.8 months and OS was 76.7 months; 5-year rwDFS and OS rates were 29.3% and 57.5%, respectively. Among 392 patients with loco-regional recurrence, the most frequently observed treatment was curative radiation monotherapy (28.2%). CONCLUSION: Despite clinical guideline recommendations, rate of adjuvant chemotherapy among patients with resected early-stage NSCLC was low in clinical practice. Overall, among patients with early-stage NSCLC treated with conventional primary surgery, poor survival outcomes were observed, highlighting the need for and importance of more effective adjuvant treatments.

Event-free survival as a predictor of overall survival and recurrence burden of patients with non-small cell lung cancer receiving neoadjuvant therapy.

OBJECTIVES: Event-free survival has replaced overall survival as a primary end point in many recent and ongoing clinical trials. This study aims to examine the correlation between real-world event-free survival and overall survival and to assess the clinical and economic burden associated with disease recurrence among patients with resected stage II to III non-small cell lung cancer who received neoadjuvant therapy in the United States. METHODS: This retrospective study used the Surveillance, Epidemiology, and End Results Medicare database (2007-2019) to identify patients with newly diagnosed, resected, stage II to IIIB (N2) non-small cell lung cancer who received neoadjuvant therapy. The correlation between real-world event-free survival and overall survival was assessed using the normal scores rank correlation and landmark analysis. Overall survival, all-cause health care resource use and costs, and non-small cell lung cancer-related health care resource use and costs were compared between patients with and without recurrence. RESULTS: A total of 221 patients met the eligibility criteria (median follow-up time from neoadjuvant treatment initiation: 32.7 months). The mean age was 72.1 years, and 57.0% of patients were male. Real-world, event-free survival and overall survival are positively and significantly correlated (0.68; 95% CI, 0.52-0.79). Patients with recurrence had significantly shorter median overall survival (19.3 vs 116.9 months), 4.59 times increased risk of death (95% CI, 2.56-8.26), and significantly higher all-cause and non-small cell lung cancer-related health care resource use and costs (adjusted mean monthly costs per patient difference: $5758 and $3187, respectively [all P < .001]). CONCLUSIONS: These findings help validate event-free survival as a clinically meaningful end point and strong predictor for overall survival and highlight the need for additional novel therapies that may delay or prevent recurrence in resectable stage II and III non-small cell lung cancer.

Evaluation of disease-free survival as a predictor of overall survival and assessment of real-world burden of disease recurrence in resected early-stage non-small cell lung cancer.

BACKGROUND: Intermediate endpoints, such as disease-free survival (DFS), have shown good correlation with overall survival (OS) in early-stage non-small cell lung cancer (NSCLC) clinical trials. However, real-world data are limited, and no previous real-world study has quantified the clinical and economic burden of disease recurrence. OBJECTIVE: To examine the association between real-world DFS (rwDFS) and OS and quantify the association between NSCLC recurrence and health care resource utilization (HCRU), health care costs, and OS in patients with resected early-stage NSCLC in the United States. METHODS: Data from the Surveillance, Epidemiology, and End Results-Medicare database (2007-2019) for patients with newly diagnosed stage IB (tumor size ≥ 4 cm) to IIIA (American Joint Committee on Cancer 7th edition) NSCLC who underwent surgery for primary NSCLC were analyzed in this retrospective observational study. Baseline patient demographic and clinical characteristics were described. rwDFS and OS were compared between patients with vs without recurrence using Kaplan-Meier curves and the log-rank test; their correlation was assessed using normal scores rank correlation. All-cause and NSCLC-related HCRU and health care costs were summarized, and mean monthly allcause and NSCLC-related health care costs were compared between cohorts using generalized linear models. RESULTS: Of the 1,761 patients who underwent surgery, 1,182 (67.1%) had disease recurrence; these patients had shorter OS from the index date and shorter subsequent OS at each postsurgery landmark (ie, 1, 3, and 5 years) than those without recurrence (all P < 0.001). OS and rwDFS were significantly correlated (0.57; P < 0.001). Patients with recurrence also had significantly higher all-cause and NSCLC-related HCRU and mean monthly all-cause and NSCLC-related health care costs during the study period. CONCLUSIONS: Postsurgery rwDFS was significantly correlated with OS in patients with early-stage NSCLC. Patients with postsurgery recurrence had a higher risk of death and incurred higher HCRU and health care costs than those without recurrence. These findings highlight the importance of preventing or delaying recurrence in patients with resected NSCLC. DISCLOSURES: Dr West is Senior Medical Director at AccessHope and an Associate Professor at City of Hope. He also serves on the advisory board for Amgen, AstraZeneca, Genentech/Roche, Gilead, Merck, Mirati Therapeutics, Regeneron, Summit Therapeutics, and Takeda and as a speaker for AstraZeneca and Merck. Drs Hu, Chirovsky, and Samkari are employees of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA and own stock/stock options in Merck & Co., Inc., Rahway, NJ, USA. Drs Zhang, Song, Gao, and Signorovitch, Mr Lerner, and Ms Jiang are employees of Analysis Group, Inc., a consulting company that has provided paid consulting services to Merck Sharp & Dohme LLC., a subsidiary of Merck & Co., Inc., Rahway, NJ, USA, which funded the development and conduct of this study and article. This study used the linked SEER-Medicare database. The interpretation and reporting of these data are the sole responsibility of the authors. The collection of cancer incidence data used in this study was supported by the California Department of Public Health pursuant to California Health and Safety Code Section 103885; Centers for Disease Control and Prevention's National Program of Cancer Registries, under cooperative agreement 5NU58DP006344; the National Cancer Institute's SEER Program under contract HHSN261201800032I awarded to the University of California, San Francisco, contract HHSN261201800015I awarded to the University of Southern California, and contract HHSN261201800009I awarded to the Public Health Institute. The ideas and opinions expressed herein are those of the authors and do not necessarily reflect the opinions of the State of California, Department of Public Health, the National Cancer Institute, and the Centers for Disease Control and Prevention or their contractors and subcontractors.

Cost-effectiveness of pembrolizumab for the first-line treatment of recurrent or metastatic head and neck squamous cell carcinoma in the United States.

AIMS: Pembrolizumab, as monotherapy in first-line recurrent or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) with a combined positive score (CPS) ≥1 and in combination with platinum and 5-fluorouracil (5-FU) in the overall R/M HNSCC population, received US FDA approval based on the KEYNOTE-048 trial. Using public drug prices, from a US payer perspective, we evaluated the cost-effectiveness of each pembrolizumab regimen vs. cetuximab + platinum+5-FU (EXTREME regimen, trial comparator), cisplatin + docetaxel + cetuximab (TPEx regimen), cisplatin + paclitaxel, and platinum+5-FU. METHODS: A three-state partitioned-survival model was used to project costs and outcomes over 20 years with 3% annual discounting. Progression-free and overall survival were modeled using long-term extrapolation of KEYNOTE-048 data and, for alternative comparators, data from a network meta-analysis was used. Time-on-treatment was derived from KEYNOTE-048 or approximated using network meta-analysis progression-free survival estimates. Costs included first-line and subsequent treatments, disease management, adverse events, and terminal care costs. Utilities were derived from the KEYNOTE-048 Euro-QoL five-dimension data and using a US algorithm. RESULTS: In the CPS ≥1 R/M HNSCC population, pembrolizumab monotherapy was dominant vs. EXTREME and TPEx regimens, and cost-effective (at $100,000/QALY threshold) vs. platinum+5-FU ($86,827/QALY) and cisplatin + paclitaxel ($81,473/QALY). Pembrolizumab combination therapy in the overall R/M HNSCC population was dominant vs. TPEx regimen, and cost-effective vs. EXTREME regimen ($1769/QALY), platinum+5-FU ($81,989/QALY), and cisplatin + paclitaxel ($89,505/QALY). Sensitivity analyses showed a high cost-effectiveness probability for pembrolizumab at the $100,000/QALY threshold. CONCLUSIONS: First-line pembrolizumab monotherapy in patients with CPS ≥1, and pembrolizumab combination therapy in the overall R/M HNSCC population is cost-effective from the perspective of the US payers.

Correlation Between Early Time-to-Event Outcomes and Overall Survival in Patients With Locally Advanced Head and Neck Squamous Cell Carcinoma Receiving Definitive Chemoradiation Therapy: Systematic Review and Meta-Analysis.

Background: Overall survival (OS) is the most patient-relevant outcome in oncology; however, in early cancers, large sample sizes and extended follow-up durations are needed to detect statistically significant differences in OS between interventions. Use of early time-to-event outcomes as surrogates for OS can help facilitate faster approval of cancer therapies. In locally advanced head and neck squamous cell carcinoma (LA-HNSCC), event-free survival (EFS) was previously evaluated as a surrogate outcome (Michiels 2009) and demonstrated a strong correlation with OS. The current study aimed to further assess the correlation between EFS and OS in LA-HNSCC using an updated systematic literature review (SLR) focusing on patients receiving definitive chemoradiation therapy (CRT). Methods: An SLR was conducted on May 27, 2021 to identify randomized controlled trials assessing radiotherapy alone or CRT in the target population. Studies assessing CRT and reporting hazard ratios (HRs) or Kaplan-Meier data for OS and EFS were eligible for the analysis. CRT included any systemic treatments administered concurrently or sequentially with radiation therapy. Trial-level EFS/OS correlations were assessed using regression models, and the relationship strength was measured with Pearson correlation coefficient (R). Correlations were assessed across all CRT trials and in trial subsets assessing concurrent CRT, sequential CRT, RT+cisplatin, targeted therapies and intensity-modulated RT. Subgroup analysis was conducted among trials with similar EFS definitions (i.e. EFS including disease progression and/or death as events) and longer length of follow-up (i.e.≥ 5 years). Results: The SLR identified 149 trials of which 31 were included in the analysis. A strong correlation between EFS and OS was observed in the overall analysis of all CRT trials (R=0.85, 95% confidence interval: 0.72-0.93). Similar results were obtained in the sensitivity analyses of trials assessing concurrent CRT (R=0.88), sequential CRT (R=0.83), RT+cisplatin (R=0.82), targeted therapies (R=0.83) and intensity-modulated RT (R=0.86), as well as in trials with similar EFS definitions (R=0.87), with longer follow-up (R=0.81). Conclusion: EFS was strongly correlated with OS in this trial-level analysis. Future research using individual patient-level data can further investigate if EFS could be considered a suitable early clinical endpoint for evaluation of CRT regimens in LA-HNSCC patients receiving definitive CRT.

Pembrolizumab alone or with chemotherapy for recurrent or metastatic head and neck squamous cell carcinoma: Health-related quality-of-life results from KEYNOTE-048.

OBJECTIVES: To assess health-related quality of life (HRQoL) with first-line pembrolizumab, pembrolizumab-chemotherapy, or cetuximab-chemotherapy in recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC) in the phase 3 KEYNOTE-048 trial (NCT02358031). MATERIALS AND METHODS: HRQoL was measured using the European Organisation for Research and Treatment of Cancer 30-question quality-of-life (EORTC QLQ-C30), the EORTC 35-question quality-of-life head and neck cancer-specific module (EORTC QLQ-H&N35), and the EuroQol 5-dimension 3-level instruments (EQ-5D-3L). Secondary endpoints included mean change from baseline in EORTC QLQ-C30 global health status/quality of life (GHS/QoL) at week 15 and time to deterioration (TTD) in EORTC QLQ-C30 GHS/QoL and EORTC QLQ-H&N35 pain and swallowing. RESULTS: Of 882 enrolled participants, 844 received ≥ 1 dose of study treatment and completed ≥ 1 HRQoL assessment; adherence was ≥ 79% at week 15 across treatment groups. At week 15, EORTC QLQ-C30 GHS/QoL scores remained stable; no clinically meaningful between-group differences were observed (least squares mean difference, pembrolizumab vs cetuximab-chemotherapy, 0.24; 95% CI, -3.34 to 3.82; pembrolizumab-chemotherapy vs cetuximab-chemotherapy, 0.40; 95% CI, -3.46 to 4.26). Median TTD in EORTC QLQ-C30 GHS/QoL and EORTC QLQ-H&N35 pain and swallowing scores was not reached over 51 weeks across groups, showing stable HRQoL. TTD was similar between groups for EORTC QLQ-C30 GHS/QoL (pembrolizumab vs cetuximab-chemotherapy: HR, 1.38; 95% CI, 0.95-2.00; pembrolizumab-chemotherapy vs cetuximab-chemotherapy: HR, 1.37; 95% CI, 0.94-2.00), as was TTD in EORTC QLQ-H&N35 pain and swallowing scores. CONCLUSIONS: Pembrolizumab monotherapy and pembrolizumab-chemotherapy extended OS while maintaining HRQoL, further supporting first-line use for R/M HNSCC.

Cost-Effectiveness of Pembrolizumab Regimens for the First-Line Treatment of Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma in Argentina.

INTRODUCTION: The phase III KEYNOTE-048 trial showed that the programmed death receptor 1 (PD-1) inhibitor pembrolizumab, in the combined positive score (CPS) ≥ 1 population and combined with platinum + 5-fluorouracil in the total population, improves survival over cetuximab + platinum + 5-fluorouracil in recurrent or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC). We evaluated the cost-effectiveness of pembrolizumab as monotherapy in the CPS ≥ 1 population or combined with platinum + 5-fluorouracil in the total population versus cetuximab + platinum + 5-fluorouracil from the social security perspective in Argentina. METHODS: A partitioned survival model projected costs and outcomes over 20 years with 3% annual discounting. Health state occupancy was modeled using KEYNOTE-048 Kaplan-Meier curves until the final analysis data cutoff, followed by parametric extrapolations guided by statistical criteria. Costs for initial and subsequent treatments, disease and adverse events management, and terminal care were included (AR $74.00 = 1 USD). Time-on-treatment and EuroQol five-dimension scores were taken from KEYNOTE-048. Utilities were derived using an Argentina-specific algorithm. RESULTS: With pembrolizumab monotherapy, patients accrued 1.1040 additional life-years and 0.8768 additional quality-adjusted life-years (QALYs), for incremental cost-effectiveness ratios (ICERs) of AR $135,801/life-year and AR $170,985/QALY gained over cetuximab + platinum + 5-fluorouracil. Additional life-years and QALYs gained with pembrolizumab combination therapy versus cetuximab + platinum + 5-fluorouracil were 1.3296 and 1.0536, respectively (ICERs of AR $680,143/life-year and AR $858,306/QALY). Considering a threshold of AR $1,676,122/QALY gained, pembrolizumab monotherapy and combination therapy had an 88.0% and a 77.1% probability of being cost-effective, respectively. CONCLUSION: Pembrolizumab either as monotherapy or in combination with chemotherapy offers substantial survival gains for patients with R/M HNSCC at small additional costs, making it a cost-effective treatment versus cetuximab + platinum + 5-FU in Argentina.

Corrigendum: Economic Value of Lost Productivity Attributable to Human Papillomavirus Cancer Mortality in the United States.

[This corrects the article DOI: 10.3389/fpubh.2020.624092.].