Impact of Workforce Challenges and Funds Flow on Cancer Clinical Trial Development and Conduct.

The conduct of clinical cancer research has faced considerable challenges in recent years, and the situation has only been exacerbated by the global pandemic. The growing complexity of clinical trials and rising administrative burdens had been causing greater expense and difficulty in recruiting and retaining an appropriately trained workforce even before the well-publicized increase in turnover caused by the pandemic. Longstanding issues such as restrictive inclusion criteria and complicated trial designs have negatively affected already low clinical trial accrual rates, limited sites capable of opening studies and enrolling patients, and worsened disparities in trial participation. Opposing these elements are efforts by ASCO and other organizations to increase affordability, access, and equity in clinical trial enrollment. To provide diverse perspectives on how these challenges are affecting cancer research as we emerge from the pandemic, we asked a panel of experienced clinical research leaders from both academic and community cancer centers to answer questions they felt most pressing about the business of conducting clinical research today and where they felt the field was moving in the near future.

Access to Cancer Specialist Care and Treatment in Patients With Advanced Stage Lung Cancer.

BACKGROUND: Access to specialty care is critical for patients with advanced stage lung cancer. This study assessed access to cancer specialists and cancer treatment in a broad population of patients with advanced stage lung cancer. MATERIALS AND METHODS: Two study samples were extracted from 2 claims databases and analyzed independently: patients aged ≥ 18 years with de novo diagnosis of metastatic lung cancer in the MarketScan database between 2008 and 2014 (commercially insured adult patients; n = 22,268); and patients aged ≥ 65 years in the Surveillance, Epidemiology, and End Results-Medicare database with a diagnosis of advanced non-small-cell lung cancer between 2007 and 2011 (Medicare-insured elderly patients; n = 9651). The study period spanned from 6 weeks before the first lung biopsy tied to the initial lung cancer diagnosis until the end of continuous health insurance enrollment, or data availability, or death. RESULTS: Among the commercially insured adults (MarketScan), most patients were seen by a cancer specialist within a month of first lung biopsy (80%), 12% were never seen by a cancer specialist, and 6% did not receive cancer-directed therapy. Among the Medicare-insured elderly patients (SEER-Medicare), the proportions were 79%, 4%, and 10%, respectively. Patients seen by a cancer specialist were more likely to receive cancer-directed therapy (95% vs. 92%, P < .001 and 92% vs. 38%, P < .001, respectively). CONCLUSION: Between 4% and 12% of patients with advanced stage lung cancer do not have appropriate access to cancer specialist, which appears to negatively affect access to optimal and timely treatment.

National Cancer Database Analysis of Proton Versus Photon Radiation Therapy in Non-Small Cell Lung Cancer.

PURPOSE: To analyze outcomes and predictors associated with proton radiation therapy for non-small cell lung cancer (NSCLC) in the National Cancer Database. METHODS AND MATERIALS: The National Cancer Database was queried to capture patients with stage I-IV NSCLC treated with thoracic radiation from 2004 to 2012. A logistic regression model was used to determine the predictors for utilization of proton radiation therapy. The univariate and multivariable association with overall survival were assessed by Cox proportional hazards models along with log-rank tests. A propensity score matching method was implemented to balance baseline covariates and eliminate selection bias. RESULTS: A total of 243,822 patients (photon radiation therapy: 243,474; proton radiation therapy: 348) were included in the analysis. Patients in a ZIP code with a median income of <$46,000 per year were less likely to receive proton treatment, with the income cohort of $30,000 to $35,999 least likely to receive proton therapy (odds ratio 0.63 [95% confidence interval (CI) 0.44-0.90]; P=.011). On multivariate analysis of all patients, non-proton therapy was associated with significantly worse survival compared with proton therapy (hazard ratio 1.21 [95% CI 1.06-1.39]; P<.01). On propensity matched analysis, proton radiation therapy (n=309) was associated with better 5-year overall survival compared with non-proton radiation therapy (n=1549), 22% versus 16% (P=.025). For stage II and III patients, non-proton radiation therapy was associated with worse survival compared with proton radiation therapy (hazard ratio 1.35 [95% CI 1.10-1.64], P<.01). CONCLUSIONS: Thoracic radiation with protons is associated with better survival in this retrospective analysis; further validation in the randomized setting is needed to account for any imbalances in patient characteristics, including positron emission tomography-computed tomography staging.

Trends, predictors, and impact of systemic chemotherapy in small cell lung cancer patients between 1985 and 2005.

BACKGROUND: The last 3 decades have witnessed limited therapeutic advances in small cell lung cancer (SCLC) management. This study evaluated real-world trends in the use of systemic therapies and the impact on patient outcomes in the United States. METHODS: The Surveillance, Epidemiology, and End Results-Medicare database was used to find patients diagnosed with SCLC between 1985 and 2005. The 1985-1990 period served as the baseline for a temporal analysis conducted at 5-year intervals (1985-1990, 1991-1995, 1996-2000, and 2001-2005). Cox proportional models were used to estimate the effect of chemotherapy on survival. Results were validated with a propensity-matched analysis. RESULTS: There were 47,351 eligible patients: 52% were male; the median age was 71 years; and 87% were white, 7% were black, and 1.4% were Asian. The proportion of patients treated with chemotherapy was low but increased over time (38%, 55%, 50%, and 53%; P < .001). Race, diagnosis period, age, stage, and location of residence significantly predicted chemotherapy use. Females (51%), Asians (53%), and rural residents (60%) were more likely to receive chemotherapy. The median overall survival with and without chemotherapy was 9.6 and 3.6 months, respectively. Linear trend analyses showed a modest reduction in the impact of chemotherapy on survival for patients treated with chemotherapy versus untreated patients (hazard ratios [HRs], 0.59, 0.61, 0.64, and 0.62; P < .001) but an overall trend of improved survival for treated (HRs, 1.0, 1.03, 1.00, and 0.96; P = .005) and untreated patients (HRs, 1.0, 0.99, 0.94, and 0.92; P < .001). There was no survival difference between patients treated with carboplatin and patients treated with cisplatin (HR, 0.99; confidence interval [CI], 0.81-1.19; P = .875). Additional therapy beyond platinum-based chemotherapy was associated with a survival benefit (HR, 0.78; CI, 0.75-0.81; P < .001). CONCLUSIONS: Chemotherapy use was associated with a survival benefit in Medicare patients with SCLC treated in a real-world setting.

Necitumumab in Metastatic Squamous Cell Lung Cancer: Establishing a Value-Based Cost.

IMPORTANCE: The SQUIRE trial demonstrated that adding necitumumab to chemotherapy for patients with metastatic squamous cell lung cancer (mSqCLC) increased median overall survival by 1.6 months (hazard ratio, 0.84). However, the costs and value associated with this intervention remains unclear. Value-based pricing links the price of a drug to the benefit that it provides and is a novel method to establish prices for new treatments. OBJECTIVE: To evaluate the range of drug costs for which adding necitumumab to chemotherapy could be considered cost-effective. DESIGN, SETTING, AND PARTICIPANTS: We developed a Markov model using data from multiple sources, including the SQUIRE trial, which compared standard chemotherapy with and without necitumumab as first-line treatment of mSqCLC, to evaluate the costs and patient life expectancies associated with each regimen. In the analysis, patients were modeled to receive gemcitabine and cisplatin for 6 cycles or gemcitabine, cisplatin, and necitumumab for 6 cycles followed by maintenance necitumumab. Our model's clinical inputs were the survival estimates and frequency of adverse events (AEs) described in the SQUIRE trial. Log-logistic models were fitted to the survival distributions in the SQUIRE trial. The cost inputs included drug costs, based on the Medicare average sale prices, and costs for drug administration and management of AEs, based on Medicare reimbursement rates (all in 2014 US dollars). MAIN OUTCOMES AND MEASURES: We evaluated incremental cost-effectiveness ratios (ICERs) for the use of necitumumab across a range of values for its cost. Model robustness was assessed by probabilistic sensitivity analyses, based on 10 000 Monte Carlo simulations, sampling values from the distributions of all model parameters. RESULTS: In the base case analysis, the addition of necitumumab to the treatment regimen produced an incremental survival benefit of 0.15 life-years and 0.11 quality-adjusted life-years (QALYs). The probabilistic sensitivity analyses established that when necitumumab cost less than $563 and less than $1309 per cycle, there was 90% confidence that the ICER for adding necitumumab would be less than $100 000 per QALY and less than $200 000 per QALY, respectively. CONCLUSIONS AND RELEVANCE: These findings provide a value-based range for the cost of necitumumab from $563 to $1309 per cycle. This study provides a framework for establishing value-based pricing for new oncology drugs entering the US marketplace.

Real-world effectiveness of systemic agents approved for advanced non-small cell lung cancer: a SEER-Medicare analysis.

OBJECTIVES: Disparity exists between patients with lung cancer enrolled in clinical trials and patients treated in the community setting. This study assessed the real-world effectiveness of cytotoxic agents that became available for the treatment of non-small cell lung cancer (NSCLC) in the last 2 decades. METHODS: We employed the linked Surveillance, Epidemiology, and End Results (SEER)-Medicare database for patients diagnosed with stage IIIB/IV NSCLC between 1988 and 2005 to assess the effectiveness of newly approved agents. Effectiveness of specific agents was assessed at time periods immediately following the approval of the agent for NSCLC: baseline, 1988-1994; platinum, 1995-1999; docetaxel, 1999-2003; pemetrexed and bevacizumab, 2004-2005. Significant associations between specific drug treatment and survival improvement were determined using the Kaplan-Meier method, Cox proportional hazard model, and propensity score analyses. Significant differences were established by log-rank test. RESULTS: This analysis employed data from 143,548 patients by sex (58% male, 42% female), cancer stage (35% stage IIIB, 65% stage IV), and age (12% 20-64 years, 22% 65-69 years, 45% 70-79 years, 22% 80 years and older). There was temporal improvement in survival for patients treated with newly approved chemotherapy (1-year survival rates: 32.41% in 1988-1994, 32.95% in 1995-1998, 37.40% in 1999-2003, and 39.55% in 2004-2005). Patients treated with a newly approved drug during the relevant treatment era had a significant reduction in the risk of death when compared with patients treated with chemotherapy other than the newly approved agent (hazard ratios [95% confidence interval] were 0.76 [0.71-0.81] for platinum, 0.73 [0.70-0.75] for docetaxel, 0.40 [0.37-0.44] for pemetrexed, and 0.33 [0.27-0.40] for bevacizumab; p < .001). Propensity score adjustment did not significantly alter these results. CONCLUSIONS: Currently approved drugs for the treatment of advanced NSCLC are associated with improved survival in the U.S. Medicare patient population. Our findings support the effectiveness of these agents in the real-world oncology practice.

Lung cancer in elderly patients: an analysis of the surveillance, epidemiology, and end results database.

PURPOSE: To study the burden and outcome of lung cancer in the elderly, particularly for patients aged 80 years and older. PATIENTS AND METHODS: The national Surveillance, Epidemiology, and End Results database was analyzed for lung cancer outcomes during the period 1988 to 2003. A comparison was carried out between patients with lung cancer 80 years and older, 70 to 79 years, and younger than 70 years for demographics; stage distribution; 5-year relative survival; and survival based on histology, sex, race, stage, and treatment. The temporal trends in survival during the years 1988 to 1997 and 1998 to 2003 were also analyzed. RESULTS: Of 316,682 patients eligible for the analysis, 45,912 (14%) were 80 years or older (ie, very elderly); 103,963 (33%) were 70 to 79 years; and 166,807 (53%) were younger than 70 years. The distribution by stage and histology was comparable for all the three groups. Overall survival rate at 5 years was lower in the very elderly (7.4% v 12.3% v 15.5%; P < .0001) across sex, histologic subtypes, stages, and racial categories. Patients aged 80 years or older were less likely to receive local therapy (no surgery or radiation) than younger patients (47% v 28% and 19% for the age subgroups >/= 80 years, 70 to 79 years, and < 70 years, respectively). Overall outcomes for patients who underwent surgical therapy or radiation were comparable across the three age groups. In general, survival outcomes for the subgroup aged 70 to 79 years were similar to those of the subgroup aged 80 years and older who received single modality local therapy. CONCLUSION: Patients 80 years or older account for 14% (70 years or older accounted for 47%) of all lung cancers, are less likely to be subjected to surgery or radiation, and have inferior outcomes when compared with younger patients.