Key research presented Sunday, August 7, at the WCLC 2022 ranged from recent clinical trials demonstrating the importance of lung cancer screening to new data on sotorasib.
Chi-Fu Jeffrey Yang, MD, presented two significant studies. In the first study (abstract 2518), researchers from Massachusetts General Hospital, Boston, concluded that younger patients with lung cancer are significantly more likely than older patients to be diagnosed with later stages of disease, illustrating the need to develop strategies to increase the early detection of lung cancer among younger patients who are currently ineligible for lung cancer screening.
The research team examined data from patients between 20 and 80 years of age in the US Cancer Statistics database and National Cancer Database diagnosed with non-small-cell lung cancer (NSCLC). The research team found that more than 75% of patients aged 20-29 were diagnosed with stage IV disease compared to only 40% of patients aged 70-79. The percentage of lung cancers diagnosed at stage IV among younger patients under age 50 years did not change between 2010 and 2018, while the percentage of lung cancers diagnosed at stage IV among patients >50 years significantly decreased during this period. The researchers observed a shift toward earlier stages of disease among patients aged 50-59, 60-69, and 70-79, while no stage shift was observed among patients aged 20-29, 30-39, or 40-49.
“In this national analysis of patients diagnosed with lung cancer from 2010 to 2018, we found that over 64% of younger adults diagnosed with lung cancer continue to be identified late in their disease course,” said Dr. Yang, a thoracic surgeon at Massachusetts General Hospital and assistant professor of surgery at Harvard Medical School. “Different tumor biology, delays in diagnosis, and the absence of methods to facilitate early detection among young adults likely contribute to the high rate of stage IV disease diagnosed in this population.”
Dr. Yang noted that median survival of young adults diagnosed with lung cancer increased by 14 months from 2010 to 2018, largely due to improvements in survival for patients with advanced disease. However, five-year survival of younger patients with stage IV disease was still only 10% to 15%, he said. Strategies to increase the early detection of lung cancer among younger patients who are currently ineligible for lung cancer screening are urgently needed, he concluded.
In the second study (abstract 2534), researchers from Massachusetts General Hospital analyzed data from the National Lung Screening Trial (NLST) and found that the incidence of second primary lung cancer was approximately 4% among the entire cohort of lung cancer patients and was as high as 8% among patients undergoing surgery for stage IA disease.
Among patients diagnosed with stage I-III lung cancer in the NLST, 6% of patients developed a second primary lung cancer and the rate of second primary lung cancer was 1% to 2% per patient-year, Dr. Yang reported. The median time to diagnosis of metachronous primary lung cancers was 2.7 years, and 27% of second primaries were diagnosed more than four years after the date of first primary lung cancer diagnosis, illustrating the importance of lifelong follow-up, he added.
NELSON Trial Protocol More Sensitive than NLST and May Increase the Benefits of Lung Cancer Screening While Reducing Unnecessary Follow-up Procedures
The protocol used to screen and detect lung cancer in the NELSON Trial is more sensitive than the protocol used in the NLST, particularly for early-stage cancers, according to research (abstract 1687) reported by Koen de Nijs, a PhD candidate at the Public Health department of the Erasmus University Medical Center, Rotterdam, the Netherlands.
The Dutch-Belgian Lung Cancer Screening trial (Nederlands-Leuvens Longkanker Screenings Onderzoek [NELSON]) demonstrated a reduction in lung cancer mortality of 24% for screening with low-dose computed tomography (CT), compared to the 20% found in the NLST, Dr. de Nijs said. NELSON and NLST differed in study population and trial design. Specifically, in contrast to the NLST, the NELSON trial employed a nodule management protocol that incorporated nodule volume and quantified volume growth as opposed to nodule diameter.
Dr. de Nijs found that the sensitivity in NELSON was estimated to be higher across all stages compared with the NLST. In particular, CT sensitivity was considerably higher for early-stage adenocarcinoma (for stage 1A, 73% in NELSON vs. 57% in the NLST; for stage 1B, 90% in NELSON vs. 64% in the NLST), and stage 2 squamous cell carcinoma (75% in NELSON vs. 39% in the NLST).
“Model-based comparison of the NELSON and NLST suggests that the differences in screening effectiveness may be explained by differences in the nodule management protocols,” Dr. de Nijs said. “The protocol used in NELSON was more sensitive than the protocol used in the NLST, particularly for early-stage cancers. Furthermore, the protocol used in NELSON also had improved specificity.”
CodeBreaK 100/101: First Report of Safety/Efficacy of Sotorasib in Combination with Pembrolizumab or Atezolizumab in Advanced KRAS p.G12C NSCLC
Using sotorasib as a lead-in therapy with pembrolizumab or atezolizumab for patients with advanced KRAS p.G12C NSCLC demonstrated durable clinical activity with lower rates of grade 3/4 treatment-related adverse events compared to patients who received these therapies concurrently, according to research (abstract 676) presented by Bob T. Li, MD, PhD, MPH, a medical oncologist at Memorial Sloan Kettering Cancer Center, New York, NY.
Sotorasib monotherapy has demonstrated a durable objective response rate of 41%, and 33% two-year overall survival in advanced, pretreated KRAS p.G12C-mutated NSCLC. In preclinical studies, sotorasib combined with anti-PD-1 therapy increased CD8+ T-cell infiltration and enhanced anti-tumor efficacy. Dr. Li and colleagues from multiple clinical trial sites initiated CodeBreak 100/101 phase 1b dose exploration to provide the first assessment of the safety and efficacy of sotorasib with either pembrolizumab or atezolizumab anti-PD-1/PD-L1 immunotherapy.
“Combining sotorasib with pembrolizumab or atezolizumab in advanced KRAS p.G12C NSCLC led to a higher incidence of grade 3/4 treatment-related adverse events than previously observed with monotherapy, primarily liver enzyme elevations,” Dr. Li said. “However, these effects may be mitigated by dose reduction and lead-in administration of sotorasib. Dose expansion is ongoing in treatment-naïve patients using sotorasib lead-in followed by combination with pembrolizumab as a potential first-line treatment.”
IASLC Early Detection and Screening Committee to Report on Global Obstacles to Lung Cancer Screening
Also on Sunday, a representative from the Diagnostics Working Group of the IASLC Early Detection and Screening Committee announced an effort (abstract 695) to outline the current obstacles and perspectives of lung cancer screening in low- and middle-income countries, and to propose guidance, recommendations, and future research strategies.
“Specific risks for lung cancer in specific regions have to be taken into account,” said Milena Cavic, PhD, co-chair of the Diagnostics Working Group of the Screening and Early Detection Committee, from the Institute for Oncology and Radiology of Serbia.
“Broader discussion on this matter is globally important, both for low-to-middle-income and high-income countries,” she said. “Many countries are planning to introduce lung cancer screening, taking into account all the governmental, healthcare, and population-specific parameters important for this delicate process; thus evidence-based guidelines are of utmost importance.”
Dr. Cavic asked attendees to help the working group in its efforts by following the QR code above to a questionnaire on the status and challenges of lung cancer screening worldwide.