The Effect of Advances in Lung-Cancer Treatment on Population Mortality
Updated TNM Staging System For SCLC Offers Better Predictive Power
Photo Credit: Mohammed Haneefa Nizamudeen
Researchers recently validated the ninth edition of the TNM staging system for SCLC, finding improved accuracy and predictive power.
The tumor-node-metastasis (TNM) staging system plays a critical role in the prognostic assessment and treatment decisions for lung cancer. Guidelines recommend treatment modalities for patients with small-cell lung cancer (SCLC), which accounts for approximately 10% of the global incidence of lung cancer, based on the TNM classification.
The ninth edition of the TNM staging system (TNM-9) of lung cancer was presented at the 2023 World Conference on Lung Cancer, but there remained a need for proper external validation of the staging system. Previously, researchers validated the TNM-9 using data from the Surveillance, Epidemiology, and End Results (SEER) database from patients with non-small cell lung cancer who underwent lung resection. However, limited by flaws in the SEERS database, researchers could not further differentiate between N2a and N2b classifications.
To address this, and externally validate the TNM-9, researchers examined multicenter data from patients with limited-stage SCLC. The findings were reported in Lung Cancer.
The multicenter study included 408 patients diagnosed with limited-stage SCLC from 2004 to 2021 who underwent lung resection. The majority (86.8%) of patients were men. Most of the cohort (65.7%) were aged 65 or younger; 34.3% were older than 65 years. Surgical approaches included lobectomy (80.4%), sublobectomy (7.8%), and pneumonectomy (11.8%).
Researchers found that the TNM-9 staging system had improved distinguishing ability versus the eighth edition. These findings were observed across all stage groups that were compared (all P<0.05):
Additionally, the TNM-9 demonstrated better predictive power and accuracy for the overall survival (OS) of patients with SCLC compared with the eighth edition:
"Our external validation demonstrates that the ninth edition of pathological TNM staging for limited-stage SCLC is reasonable and valid based on a multicenter study," investigators wrote. "The ninth edition has better prognostic accuracy than the eighth edition."
ADRIATIC Study Shows Durvalumab Boosts Survival In Limited-Stage SCLC
David Spigel, MD, discusses the findings from and methodology behind the ADRIATIC study of durvalumab as consolidation therapy for patients with limited-stage small cell lung cancer.
David Spigel, MD, chief scientific officer at Sarah Cannon Research Institute in Nashville, Tennessee, discusses the findings from and methodology behind the ADRIATIC study (NCT03703297) of durvalumab (Imfinzi) as consolidation therapy for patients with limited-stage small cell lung cancer (SCLC) that had not worsened after standard chemoradiotherapy.
According to data from the first planned analysis of the trial presented at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting, durvalumab significantly improved overall survival and progression-free survival vs placebo when given as a treatment for patients with limited-stage SCLC. For safety, the adverse events observed in the study were similar between the durvalumab and placebo groups.
Transcription:
0:10This was a large trial. It was a randomized, phase 3, double-blind, placebo-controlled trial run around the world. The patients were randomized to get durvalumab after chemoradiation, durvalumab, and placebo, or a combination of durvalumab and a CTLA4 antibody, tremelimumab.
0:34The analysis we presented [at ASCO] was the first planned interim analysis of the primary end points for durvalumab vs placebo. That analysis had 2 primary end points: overall survival and progression-free survival by blinded independent central review. There are additional analyses planned for the tremelimumab arm, as well as things like quality-of-life and other safety end points. Those will come out, specifically the tremelimumab comparison, with a later interim analysis.
1:13The study met both of its primary end points. Durvalumab improved overall survival with a hazard ratio of 0.73 that corresponds to a 27% reduction in the risk of death compared with placebo. The median survival was improved by approximately 2 years. So, a 22.5-month improvement in median overall survival with durvalumab. [For] the second primary end point, progression-free survival, the hazard ratio for benefit with durvalumab was 0.76, a 24% reduction in the risk of death or progression. That corresponded to an advantage of 7.4 months in median progression-free survival. It was fantastic that both primary end points were met.
2 Immunotherapies Show Comparable Benefits In Extensive-Stage Small Cell Lung Cancer
When added to chemotherapy, researchers found no significant difference in overall or progression-free survival between PD-1 and PD-L1 inhibitors.
Patients with extensive-stage small cell lung cancer (ES-SCLC) saw significant survival benefits when treated with either PD-1 or PD-L1 inhibitors combined with chemotherapy, according to a new meta-analysis.1
Researchers found no significant difference in OS and PFS for patients with ES-SCLC.Image credit: utah51 – stock.Adobe.Com
The study was published in Frontiers in Oncology and included 3559 patients with ES-SCLC across 8 randomized clinical trials (RCTs). After comparing the 2 immunotherapy approaches, researchers found no significant difference in overall survival (OS) or progression-free survival (PFS) between them.
"The present study enriched the research data on PD-1 inhibitors in the first-line treatment of ES-SCLC after the inclusion of the results of tislelizumab and toripalimab, but PD-1 + Chemo versus PD-L1 + Chemo did not produce a significant improvement in OS and PFS," the authors said.
Patients who received PD-1 plus chemotherapy had a 29% reduced risk of death compared with those receiving chemotherapy alone, while those treated with PD-L1 plus chemotherapy saw a 28% reduction in mortality risk. Both treatment combinations significantly improved PFS, increasing by 41% with PD-1 inhibitors and 27% with PD-L1 inhibitors, compared with chemotherapy alone.
In indirect comparisons, researchers did not find a significant advantage of one inhibitor over the other in terms of efficacy (OS: HR, 0.99; 95% CI, 0.86-1.1; PFS: HR, 0.80; 95% CI, 0.61-1.0) or safety (HR, 1.0; 95% CI, 0.93-1.1) when added to chemotherapy. They noted that more research is needed to see how similar or different their efficacy and safety are in treating ES-SCLC.
Regarding safety, neither PD-1 nor PD-L1 inhibitors significantly increased the incidence of severe treatment-related adverse events (TRAEs) compared with chemotherapy alone, the authors found. The likelihood of experiencing grade 3 or higher TRAEs was nearly identical between the 2 treatments (HR, 1.0; 95% CI, 0.93-1.1), reinforcing the idea that both options provide added survival benefits without additional safety concerns. However, as PD-1 inhibitors block the interaction between PD-1 and its ligands, PD-L1 and PD-L2, the authors said the treatment option may lead to a higher incidence of AEs.2
Additionally, a subgroup analysis indicated that patients with ES-SCLC with higher PD-L1 expression levels (≥ 1%) may benefit slightly more from PD-1 inhibitors, while those with lower PD-L1 expression (< 1%) appeared to respond better to PD-L1 inhibitors.1 However, researchers cautioned against using PD-L1 expression as a definitive marker for treatment selection until further research confirms these findings.
A 2020 meta-analysis published in Thoracic Cancer included 4 of the 8 studies analyzed—KEYNOTE-604, IMpower133, EA5161, and CASPIAN—but came to a different conclusion about safety.3
While PD-1 and PD-L1 inhibitors combined with chemotherapy significantly improved survival in ES-SCLC, they were also linked to an increased risk of immune-related AEs (imAEs). Compared with chemotherapy alone, patients who received either combination therapy saw an almost quadrupled increase in all-grade imAEs (HR, 3.77; 95% CI, 1.99-7.15; P < .0001) and a sevenfold increase in severe imAEs, defined as grade 3 or higher (HR, 7.01; 95% CI, 2.48-19.81; P = .0002).
The current study did not assess how these treatments impact quality of life, an important factor for patients.1 According to the authors, additional research with larger, well-controlled clinical trials is needed to confirm these findings.
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