Mary Kate Shanahan’s research while affiliated with AstraZeneca and other places

Treatment options for non-small cell lung cancer (NSCLC) are evolving, given recent and expected approvals of immune checkpoint inhibitors (ICIs) targeting programmed cell death-(ligand) 1 (PD-1/PD-L1). We retrospectively evaluated outcomes among patients with resected stage IB-IIIA NSCLC tumors expressing PD-L1 using PALEOS (Pan-cAnadian Lung cancEr Observational Study) data (2016–2019). Key outcomes included PD-L1 expression rate and treatment patterns, recurrence, and median overall (mOS) and disease-free survival (mDFS) among PD-L1+ patients. Among 539 PD-L1–tested patients, 317 (58.8%) were PD-L1+ (≥1%). At diagnosis, 35.3%, 39.8%, and 24.9% of PD-L1+ patients had stage IB, II, or IIIA disease. Forty-one percent had received adjuvant therapy. At 22.6 months (median follow-up), first disease recurrence had occurred in 31.9% of patients, primarily at metastatic sites. After first metastatic recurrence, ICI regimens were the most common first systemic therapy (29.8%). mOS was not reached; mDFS was 40.0 months. At four years, DFS probability was 44%. Four-year OS and DFS rates were generally similar when stratified by PD-L1 expression (1–49% vs. ≥50%). These findings underscore the generally poor outcomes experienced by patients with early-stage, resected, PD-L1+ NSCLC after treatment with available adjuvant therapies, and provide context to recent and emerging trials of new treatment options.

Background Although therapy for limited-stage small-cell lung cancer (LS-SCLC) is administered with curative intent, most patients relapse and eventually die of recurrent disease. Chemotherapy (CT) with concurrent radiotherapy (RT) remains the standard of care for LS-SCLC; however, this could evolve in the near future. Therefore, understanding the current prognostic factors associated with survival is essential. Objective This real-world analysis examines factors associated with long-term survival in patients with LS-SCLC treated with CT in Manitoba, Canada. Methods A retrospective cohort study was conducted using Manitoba Cancer Registry and CancerCare Manitoba records. Eligible patients were aged >18 years and had cytologically confirmed LS-SCLC diagnosed between January 1, 2004, and December 31, 2018, for which they received CT ± RT. Baseline patient, disease, and treatment characteristics and survival duration, characterized as short (<6 months), medium (6−24 months), and long term (>24 months), were extracted. Overall survival (OS) was estimated at one, two, and five years and assessed using Kaplan-Meier methods and Cox proportional hazards models. Results Over the 15-year study period, 304 patients met the eligibility criteria. Long-term survivors comprised 39.1% of the cohort; at diagnosis, this subgroup was younger, more likely to have Eastern Cooperative Oncology Group Performance Status (ECOG PS) 0, and have normal lactate dehydrogenase, sodium, and hemoglobin levels. OS estimates for the entire cohort at one, two, and five years were 66%, 38%, and 18%, respectively. In the ECOG PS 0 subgroup, OS estimates at one, two, and five years were 85%, 52%, and 24%, respectively; OS estimates were 60%, 35%, and 17%, respectively, for ECOG PS 1−2 and were 47%, 23%, and 10%, respectively, for ECOG PS 3−4. OS was significantly higher among patients with normal serum sodium and hemoglobin levels than those with abnormal levels. Univariable hazard regression models found that ECOG PS, age at diagnosis, receipt of prophylactic cranial irradiation (PCI), and thoracic RT were associated with survival. On multivariable hazard regression, ECOG PS and receipt of PCI were associated with survival. Conclusion Survival for greater than two years in patients with LS-SCLC treated with CT ± RT was associated with ECOG PS and receipt of PCI.

Background Extensive-stage small-cell lung cancer (ES-SCLC) is an incurable cancer with poor prognosis in which characteristics predictive of long-term survival are debated. The utility of agents such as immune checkpoint inhibitors highlights the importance of identifying key characteristics and treatment strategies that contribute to long-term survival and could help guide therapeutic decisions. Objective This real-world analysis examines the characteristics, treatment patterns, and clinical outcomes of patients receiving chemotherapy without immunotherapy for ES-SCLC in Manitoba, Canada. Methods A retrospective cohort study assessed patient characteristics, treatment, and survival duration (short: <6 months; medium: 6–24 months; long: >24 months) using the Manitoba Cancer Registry and CancerCare Manitoba records. Eligible patients were aged >18 years with cytologically confirmed ES-SCLC diagnosed between January 1, 2004, and December 31, 2018, and received cytotoxic chemotherapy (CT). The one-, two-, and five-year probabilities of overall survival (OS) were assessed relative to patient, disease, and treatment characteristics using Kaplan-Meier methods and Cox proportional hazards models. Results This analysis included 537 patients. Cisplatin was used in 56.1% of patients, 45.6% received thoracic radiotherapy (RT), and few received prophylactic cranial irradiation (PCI). In the overall cohort, one-, two- and five-year OS rates were 26%, 8%, and 3%, respectively. For patients with Eastern Cooperative Oncology Group Performance Status (ECOG PS) 0, OS rates at one, two, and five years were 43%, 17%, and 10%, respectively, vs. 27%, 8%, and 2% for those with ECOG PS 1–2, and 16%, 3%, and 3% for those with ECOG PS 3–4. In long-term survivors, ECOG PS scores were lower and abnormal laboratory test results were less frequent. Overall, 74.4% of long-term survivors received thoracic RT and 53.5% received PCI. Known poor prognostic factors – including brain/liver metastases, high lactate dehydrogenase (LDH), abnormal sodium, and low hemoglobin levels – were less common but still seen in long-term survivors. Conclusion Although rare, patients with ES-SCLC may experience long-term survival with CT ± thoracic RT ± PCI. Factors predicting long-term survival include traditional prognostic factors such as ECOG PS, LDH level, and receipt of thoracic RT or PCI. These findings support current treatment algorithms for ES-SCLC and provide baseline survival estimates to assess the real-world impact of adding immune checkpoint inhibitors in the future.

Objectives The ADAURA trial demonstrated the benefit of adjuvant osimertinib among patients with resected, early-stage, epidermal growth factor receptor-mutated (EGFRm) non-small cell lung cancer (NSCLC). To understand the potential population impact, it is critical to deduce the prevalence, management, and outcomes of this patient population in the real-world setting before use of adjuvant osimertinib. Materials and Methods Using PALEOS (Pan-cAnadian Lung cancEr Observational Study) data (2012–2019), a retrospective, multi-center, observational cohort study was conducted among patients with early-stage (IB–IIIA) resected NSCLC who had not received neoadjuvant therapy. Study outcomes included EGFRm prevalence, treatment patterns, recurrence outcomes, and overall and disease-free survival (OS/DFS). Results Among all patients undergoing reflexive EGFRm testing by a pathologist at time of diagnosis irrespective of disease stage (N = 535), 23% were EGFRm-positive, of whom 19.2% had uncommon mutations; one result was indeterminate. Within the EGFRm-positive cohort (N = 156), mean age at diagnosis was 68 years, 65% of patients were female, and 35% were of Asian descent. At diagnosis, 48%, 31%, and 21% had stage IB, II, or IIIA disease, respectively; 46% received adjuvant therapy after resection. Half of patients experienced disease recurrence, typically involving distant sites; central nervous system metastasis varied from 12%–15.0% across disease stages. EGFR tyrosine kinase inhibitors were the most commonly received therapy after first metastatic recurrence. Median OS (DFS) was not reached, 71.2 (22.8) months, and 50.1 (18.0) months among stage IB, II, and IIIA patients. Patients with uncommon EGFRm had a lower probability of survival than those with common EGFRm (2 years: 87% vs. 91%–94%; 4 years: 56% vs. 73%–82%). Conclusion Approximately one-quarter of patients with resected, early-stage NSCLC were EGFRm-positive in this study. These patients had high recurrence rates and suboptimal long-term survival after treatment with current therapies. New adjuvant treatments are warranted.

The prognosis for extensive-stage small cell lung cancer (ES-SCLC) is poor. Real-world evidence can highlight the unmet clinical need within this population. We conducted a population-based cohort study of ES-SCLC patients diagnosed in a large Canadian province (2010–2018) using electronic medical records and administrative claims data. In all, 1941 ES-SCLC patients were included, of which 476 (25%) were recurrent cases. Median age at diagnosis was 70 years (range: 39–94) and 50.2% were men. Of the 1941 ES-SCLC patients, 29.5% received chemotherapy and radiotherapy, 17.0% chemotherapy alone, 8.7% radiotherapy alone, and 44.8% received best supportive care. Chemotherapy was initiated by 46.5%, 8.5%, and 1.4% of first-, second-, and third-line patients, with lower uptake for recurrent cases. Median survival from first-, second-, and third-line chemotherapy was 7.82 months (95% CI: 7.50–8.22), 5.72 months (95% CI: 4.90–6.87), and 3.83 months (95% CI: 2.99–4.60). Among patients who received first-line therapy, the 2-year and 5-year survival was 7.3% (95% CI: 5.7–9.2) and 2.9% (95% CI: 1.8–4.5). In conclusion, initiation of first-line treatment in ES-SCLC was low with significant attrition in subsequent lines. These results underscore the need for effective front-line treatments and highlight the potential for novel therapies to improve patient outcomes.

e20575 Background: Extensive stage small cell lung cancer (ES-SCLC) patients face a high risk of recurrence and a uniformly poor prognosis. Real-world evidence related to treatment patterns, clinical outcomes, and healthcare resource utilization is needed to highlight the unmet clinical need and demand for novel therapies within this patient population. Methods: A population-based, retrospective, longitudinal study of adult ES-SCLC patients diagnosed in the province of Alberta, Canada between January 2010 and December 2018 was conducted using provincial electronic medical records and administrative claims data. Results: A total of 1,941 ES-SCLC patients were included of which 1,465 (75%) initially presented with ES-SCLC and 476 (25%) had recurrent disease. Among newly diagnosed ES-SCLC patients, front-line therapy was as follows: 523 (35.7%) chemotherapy and radiotherapy, 280 (19.1%) chemotherapy alone, 133 (9.1%) radiotherapy alone, and 529 (36.1%) best supportive care. The primary sites of radiation were the chest (67.1%) and the brain (45.7%). Median age at diagnosis was 70 years (range: 39-94) and 50.2% were men. In contrast to the de novo patients, the majority of recurrent cases (71.6%) received no front-line therapy. In the full cohort (de novo and recurrent cases), 46.5% of patients initiated first-line, 8.7% second-line, and 1.4% third-line chemotherapy. The majority of patients received either carboplatin plus etoposide (49.5%) or cisplatin plus etoposide (43.0%) in first-line. Median overall survival was higher for patients who were treated with chemotherapy and radiotherapy (10.59 months; 95% CI: 10.03-11.61) compared to patients who received chemotherapy alone (5.65 months; 95% CI: 5.06-6.12), radiotherapy alone (3.02 months; 95% CI: 2.47-4.01), or best supportive care (0.82 months; 95% CI: 0.72-0.92; log-rank p-value < 0.001). Among patients who received first-line systemic therapy, the 1-year, 2-year and 5-year survival was 29.1% (95% CI: 26.3-32.3), 7.3% (95% CI: 5.7-9.2) and 2.9% (95% CI: 1.8-4.5), respectively and the average time spent in hospital was 17, 11, and 10 days per patient within years 1, 2, and 3, respectively. Conclusions: In a Canadian real-world setting, the initiation of first-line treatment in ES-SCLC was low with significant attrition in subsequent lines. It was evident that patients who received treatment had greater survival compared to those who do not. Collectively, these results underscore the need for effective front-line therapeutic options and highlight the potential for novel therapies to improve patient outcomes.