Brief Report on Global Clinician Practices in the First-Line Management of Metastatic Non-Small Cell Lung Cancer.

INTRODUCTION: In the dynamic landscape of metastatic NSCLC (mNSCLC) management, marked by several frontline options and the integration of next generation sequencing (NGS) for informed decision-making, barriers persist despite advancements. This includes challenges in clinical trial recruitment. To gain global insights into clinicians' practices, we conducted a survey on their testing and management approaches for patients with mNSCLC. METHODS: The survey, conducted from July 12 to August 20, 2023, utilized multiple-choice questions and qualitative research questions, employing the Likert Scale for comprehensive insights. RESULTS: A total of 127 individuals responded, with 72% affiliated with academic health systems, and 55% practicing in the USA. Regarding testing practices, 93% consistently ordered NGS for non-squamous histology, while 54% did so for squamous cell histology. Concurrent tissue and liquid biopsies were routinely ordered by 28%, while 39% reported ordering both testing platforms concurrently for select cases only. Respondents cited logistical barriers, such as insufficient tissue and lack of infrastructure, as the most common hindrance to molecular testing (76%), followed by reimbursement challenges (56%) and concerns about delayed turnaround time (50%). While most respondents were confident in interpreting NGS results, 22% lacked confidence. Concerning treatment decisions, 72% preferred awaiting molecular testing results before initiating systemic therapy. Less than 50% routinely referred patients for clinical trials in the frontline setting for mNSCLC. For patients with disease expressing high PD-L1 levels, most oncologists preferred pembrolizumab monotherapy. For disease with low PD-L1 expression, a platinum doublet chemotherapy regimen combined with pembrolizumab was favored. In disease cases with negative PD-L1 expression, a platinum doublet chemotherapy regimen with pembrolizumab was preferred. Key factors influencing oncologists' preferred immune checkpoint inhibitor (ICI) included experience with one ICI over another, preferred status per national guidelines, availability of trial data with a significant follow-up period, and consideration of drug cost. CONCLUSION: Although this study demonstrates an improved awareness and adoption of ordering NGS for the management of mNSCLC, it underscores the persistence of various barriers that must be addressed to improve upon the quality of care for patients diagnosed with mNSCLC.

Cancer Care in the Era of Artificial Intelligence.

This JAMA Oncology Patient Page explains artifical intelligence and what patients should know about how it can be used in oncology.

Frontline pembrolizumab monotherapy for metastatic non-small cell lung cancer with PD-L1 expression ≥50%: real-world outcomes in a US community oncology setting.

Background: This study investigated real-world time on treatment (rwToT) and overall survival (OS) for patients with metastatic non-small cell lung cancer (mNSCLC) who initiated first-line (1L) pembrolizumab monotherapy. We also explored discontinuation reasons and subsequent treatments, stratified by number of cycles among those who completed ≥17 cycles of 1L pembrolizumab. Methods: Patients with mNSCLC without actionable genetic aberrations, Eastern Cooperative Oncology Group performance status (ECOG PS) 0-2 and unknown, and PD-L1 TPS ≥ 50% starting 1L pembrolizumab monotherapy between 24-Oct-2016 and 31-Dec-2018 within The US Oncology Network were identified retrospectively and evaluated using structured data, with a data cutoff of 30-Sep-2021. Patient characteristics and disposition were summarized using descriptive statistics. OS and rwToT were evaluated using Kaplan-Meier method for all ECOG PS and PS 0-1. A subgroup of patients who completed ≥17 cycles were evaluated using supplemental chart review data to discern reasons for discontinuation. Results: Of the 505 patients with mNSCLC with PD-L1 TPS ≥50%, 61% had ECOG PS 0-1, 23% had ECOG PS 2, and 65% had nonsquamous histology. Median rwToT and OS of pembrolizumab were 7.0 (95% CI, 6.0-8.4) months and 24.5 (95% CI, 20.1-29.3) months, respectively. In the subgroup with ECOG PS 0-1, they were 7.6 months (95% CI, 6.2-9.2) and 28.8 months (95% CI, 22.4-37.5), respectively. Of the 103 patients who completed ≥17 cycles, 57 (55.3%) patients received 17 - 34 cycles and 46 (44.7%) patients received ≥35 cycles. Approximately 7.7% of the study population received pembrolizumab beyond 35 cycles. Most common reasons for discontinuation were disease progression (38.6%) and toxicity (19.3%) among patients who received 17-34 cycles of pembrolizumab, and disease progression (13.0%) and completion of therapy (10.9%) among patients who received ≥35 cycles. Conclusion: Consistent with findings from KEYNOTE-024 and other real-world studies, this study demonstrates the long-term effectiveness of pembrolizumab monotherapy as 1L treatment for mNSCLC with PD-L1 TPS ≥50%. Among patients who completed ≥17 cycles, nearly half completed ≥35 cycles. Disease progression and toxicity were the most common reasons for discontinuation among patients who received 17-34 cycles of pembrolizumab. Reasons for discontinuation beyond 35 cycles need further exploration.

Examining crossover and postprotocol therapies in first-line immunotherapy trials in non-small cell lung cancer (NSCLC).

BACKGROUND: Immune checkpoint inhibitor (ICI) therapy has led to significant improvement in outcomes for patients with nononcogene-driven advanced non-small cell lung cancer (NSCLC). The rate of crossover and receipt of postprotocol ICI in frontline trials for advanced NSCLC has not been systematically evaluated. METHODS: ClinicalTrials.gov was used to identify phase 3 studies evaluating the use of immunotherapy or combination chemoimmunotherapy against chemotherapy alone in the frontline management of advanced NSCLC. Data on outcomes, rate of crossover and/or subsequent post-protocol receipt of immunotherapy, and the start dates of these clinical trials were then extracted. RESULTS: Twenty-three frontline trials in nononcogene-driven advanced NSCLC were identified. Six trials with ICI monotherapy/dual ICI therapy and 17 trials evaluating chemotherapy/ICI in first-line advanced NSCLC were included in the analysis. The crossover rate ranged 0% to 54% in ICI monotherapy/dual ICI trials and 0% to 52% in chemotherapy/ICI trials. Nineteen of 23 trials provided information on subsequent postprotocol therapies. Among the trials not allowing crossover, postprotocol ICI was administered to 17% to 45.8% of patients. Information regarding the eventual receipt of ICI therapy was available for 22 of 23 trials. Of 6631 patients, 2507 (37.8%) randomized to the control arm eventually received ICI therapy. CONCLUSION: The rate of crossover and postprotocol ICI use was low in frontline trials for first-line NSCLC incorporating ICI. Given the proven survival overall survival of ICI in a broad population, there is a need to ensure availability of this life-prolonging therapy in future trials, either by crossover treatment or postprotocol administration.

Malignant Pericardial Effusion, or Fluid Around the Heart Due to Cancer.

This JAMA Oncology Patient Page describes the accumulation of excess fluid around the heart caused by cancer, known as malignant pericardial effusion.

Rapid Advances in Resectable Non-Small Cell Lung Cancer: A Narrative Review.

Importance: A series of high-profile clinical trials for patients with resectable early-stage non-small cell lung cancer (NSCLC) have recently changed the standard of care in this setting. Specifically, studies have demonstrated statistically and clinically significant improvements in efficacy with the targeted therapy for adjuvant osimertinib in patients with resected NSCLC harboring an epidermal growth factor receptor (EGFR) genomic abnormality (GA), whereas trials with chemotherapy combined with nivolumab in the neoadjuvant setting and others testing atezolizumab or pembrolizumab as adjuvant therapy have all demonstrated improvements in event-free survival (EFS) (for neoadjuvant therapy) or disease-free survival (DFS) (for adjuvant therapy). These trials introduce many open questions about how to apply these findings in clinical practice. Observations: Treatment with adjuvant osimertinib for 3 years was associated with significant improvement in both DFS and overall survival (OS), but the erosion of the DFS benefit after the duration of treatment ends suggests a potential value for more longitudinal treatment. The potential value of highly effective targeted therapies as adjuvant therapy for other GAs has a compelling rationale but no data at this time. Adjuvant atezolizumab or pembrolizumab, generally administered for 1 year after postoperative chemotherapy, are appropriate considerations, but only atezolizumab for patients with tumor programmed death-ligand 1 (PD-L1) levels of 50% has demonstrated a benefit in OS. Neoadjuvant chemotherapy with nivolumab offers a strong EFS benefit, a shorter interval of treatment, and radiographic and pathologic feedback for patients with resectable stage IB to IIIA NSCLC, although very recent randomized clinical trials of perioperative immunotherapy both combined with chemotherapy preoperatively and administered postoperatively highlight the debatable value of adjuvant immunotherapy after prior chemoimmunotherapy. Improved tumor shrinkage rates with neoadjuvant chemoimmunotherapy suggest the possibility that criteria for resectability may potentially be redefined in anticipation of a good response to neoadjuvant chemoimmunotherapy. Conclusions and Relevance: Developments in resectable NSCLC have arrived so rapidly that they have also created practical challenges of identifying optimal patients and prioritizing options among these new competing standards. In some cases, practical management requires clinical judgment and discussion with the patient to cover the gaps in prospective data. Caution should be exerted when extrapolating beyond the available data.

Targeted Therapies in Early-Stage Resectable Non-Small-Cell Lung Cancer: New Kids on the Block.

PURPOSE: With increased adoption of next-generation sequencing, tailored therapy on the basis of molecular status is being delivered for patients with early-stage resectable non-small-cell lung cancer (NSCLC). The purpose of this narrative review was to focus on recent developments of targeted therapies in the adjuvant and neoadjuvant/adjuvant setting for early-stage disease. METHODS: A systematic search of the MEDLINE/PubMed database was performed, focusing on studies published within the past 10 years. Our search queried "early-stage NSCLC (AND) tyrosine kinase inhibitor (TKI; OR) epidermal growth factor receptor (EGFR; OR) anaplastic lymphoma kinase (ALK)" and was limited only to prospective and ongoing studies. RESULTS: Most studies examining the benefit of targeted therapies in early-stage resectable NSCLC have been for EGFR-TKIs in the adjuvant setting. Currently, only one study, the ADAURA trial of adjuvant osimertinib, has demonstrated an overall survival benefit with the use of an EGFR-TKI in the adjuvant setting. Future work to build on the success of the ADAURA trial is focused on determining the optimal duration of targeted therapies and using biomarkers, such as circulating tumor DNA, to risk-stratify patients and guide maintenance targeted therapy duration. CONCLUSION: The results of several ongoing studies are eagerly awaited regarding the use of targeted therapies in the neoadjuvant/adjuvant setting and for more uncommon or rare mutations such as ALK, ROS proto-oncogene 1, rearranged during transfection, mesenchymal-epithelial transition factor, and B-Raf proto-oncogene V600E. The treatment landscape for early-stage NSCLC harboring actionable mutations is likely to shift dramatically in the upcoming decade.

Maintenance of Certification (MOC)-Benefit vs Burden.

This Viewpoint examines the demands of maintenance of certification (MOC) requirements from the ABIM on balance with the projected benefits to quality of patient care.

Pancreatic Adenocarcinoma: Real World Evidence of Care Delivery in AccessHope Data.

BACKGROUND: Pancreatic adenocarcinoma is an aggressive disease and the delivery of comprehensive care to individuals with this cancer is critical to achieve appropriate outcomes. The identification of gaps in care delivery facilitates the design of interventions to optimize care delivery and improve outcomes in this population. METHODS: AccessHope™ is a growing organization that connects oncology subspecialists with treating providers through contracts with self-insured employers. Data from 94 pancreatic adenocarcinoma cases (August 2019-December 2022) in the AccessHope dataset were used to describe gaps in care delivery. RESULTS: In all but 6% of cases, the subspecialist provided guideline-concordant recommendations anticipated to improve outcomes. Gaps in care were more pronounced in patients with non-metastatic pancreatic cancer. There was a significant deficiency in germline testing regardless of the stage, with only 59% of cases having completed testing. Only 20% of cases were receiving palliative care or other allied support services. There was no difference in observed care gaps between patients receiving care in the community setting vs. those receiving care in the academic setting. CONCLUSIONS: There are significant gaps in the care delivered to patients with pancreatic adenocarcinoma. A concurrent subspecialist review has the opportunity to identify and address these gaps in a timely manner.

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.

Challenges in synergizing radiotherapy with immunotherapy to unlock the abscopal effect in metastatic NSCLC: A systematic review.

BACKGROUND: With the recent success of immunotherapy, there is a growing interest in combining radiation with immunotherapy to boost abscopal response rates. Several challenges exist in determining how to synergize these two modalities in the treatment of metastatic NSCLC. METHODS: References for this review were identified through searches of MEDLINE/PubMed and Clinicaltrials.gov databases with the search terms "abscopal", "radiation OR radiotherapy," "NSCLC", and "lung" on the index date of July 2022 from 2000-2022. This systematic review focuses primarily on clinical papers. DISCUSSION: Early work combining radiotherapy with immunotherapy show promise in unlocking the abscopal effect. Preliminary evidence suggests that radiotherapy regimens with <5 fractions and smaller fields may be superior to regimens with 15 fractions and larger fields. There does not appear to be enough evidence to draw conclusions about the optimal timing of radiotherapy in relation to immunotherapy or the optimal anatomical location of radiation to induce the abscopal effect. Several studies suggest selecting patients with a higher absolute lymphocyte count (ALC) and lower neutrophil-to-lymphocyte ratio (NLR) may help to further boost abscopal response rates. Furthermore, selecting tumors with programmed death ligand-1 (PD-L1) expression, mismatch repair deficiency, and higher tumor mutational burden may similarly achieve this goal. Lastly, additional work is needed to minimize and predict for severe toxicity associated with combination therapy.

The Emerging Role of Radiotherapy in Oligoprogressive Non-Small Cell Lung Cancer.

Oligoprogressive disease (OPD) is an emerging concept that describes patients who have progression of disease in a limited number of metastatic sites while on systemic therapy. Growing evidence has suggested the integration of local ablative therapy with systemic agents in patients with OPD further improves survival. In oligoprogressive non-small cell lung cancer, stereotactic body radiotherapy may have an important role in the effective local control of selective progressing metastases, which may translate to better patient outcomes. This review explores the treatment paradigm of this subset of patients and provides an update on the current existing literature on this topic.

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.

ChatGPT-A promising generative AI tool and its implications for cancer care.

PLAIN LANGUAGE SUMMARY: Since its launch, ChatGPT has taken the internet by storm and has the potential to be used broadly in the health care system, particularly in a setting such as medical oncology. ChatGPT is well suited to review and extract key content from records of patients with cancer, interpret next-generation sequencing reports, and offer a list of potential clinical trial options.