David R. Spigel, MD is chief scientific officer at SCRI, wherhe oversees all scientific aspects of SCRI’s clinical trial program.

Spigel

"If you have a patient in front of you with nonsquamous, non–small cell lung cancer and early-stage disease, and you're already planning to give chemotherapy, [this molecular test is not necessary]. If you know—or the patient and their family know—that they do not want chemotherapy, [this test is also not appropriate]. However, in those patients where you're not sure [if it’s a] higher-risk cancer or whether chemotherapy should be used, this is absolutely a test that can now be ordered.”

David Spigel, MD, chief scientific officer at Sarah Cannon Research Institute, discussed findings from the international, multicenter, prospective randomized AIM-HIGH trial (NCT01817192) evaluating the utility of adjuvant chemotherapy in patients with stage IA to IIA non–small cell lung cancer (NSCLC) identified as higher risk by a 14-gene molecular assay.

Findings from the study presented at the 

 demonstrated a significant disease-free survival (DFS) benefit with adjuvant chemotherapy compared with observation in patients identified as high-risk who were randomly assigned between the study’s 2 arms.

At the 24-month landmark analysis, patients treated with adjuvant chemotherapy (n = 107) achieved a 24-month disease-free survival (DFS) rate of 96% (95% CI, 92%-100%) compared with 79% (95% CI, 70%-90%) in the observation arm (HR, 0.22; 95% CI, 0.06-0.76; 

 = .0087). Among patients with stage IA disease, a similar benefit was observed; the DFS rate was 98% (95% CI, 94%-100%) for chemotherapy (n = 58) vs 78% (95% CI, 65%-93%) for observation (n = 48; HR, 0.15; 95% CI, 0.02-0.16; 

The study included patients at least 18 years of age with completely resected, stage IA to IIA, primary nonsquamous NSCLC who had negative margins following resection. Risk stratification was completed using the 14-gene panel, and those with molecularly intermediate- or high-risk were randomly assigned 1:1 to chemotherapy or observation.

Spigel emphasized that this assay serves a practical role in clinical decision-making, particularly for patients with early-stage, nonsquamous NSCLC where the need for adjuvant therapy is uncertain. The assay identifies individuals at high risk for recurrence, allowing clinicians to tailor treatment plans more precisely. It is not intended for use in cases where adjuvant chemotherapy is already clearly indicated or definitively declined by the patient, he said.

Videos

David Spigel, MD, discusses evaluating the utility of adjuvant chemotherapy in patients with stage IA to IIA NSCLC identified as high risk by a 14-gene molecular assay.

Dr Spigel on Adjuvant Chemotherapy in Stage IA/IIA, Molecularly Higher-Risk NSCLC 

Dr Spigel on the Efficacy of Durvalumab Consolidation Therapy in LS-SCLC

David R. Spigel, MD, chief scientific officer, Sarah Cannon Research Institute, discusses findings from the first planned interim analysis of the phase 3 ADRIATIC trial (NCT03703297) in patients with limited-stage small cell lung cancer (LS-SCLC).

ADRIATIC evaluated durvalumab (Imfinzi; n = 264) vs placebo (n = 266) as consolidation therapy in patients with LS-SCLC who had received prior concurrent chemoradiotherapy. The coprimary end points of the trial were overall survival (OS) and progression-free survival (PFS) by blinded independent central review, Spigel states.

This trial met both primary end points, he reports. At a median follow-up of 37.2 months (range, 0.1-60.9) in censored patients, durvalumab elicited an OS benefit over placebo. The median OS was 55.9 months (95% CI, 37.3-not evaluable) with durvalumab vs 33.4 months (95% CI, 25.5-39.9) with placebo, resulting in a 27% reduction in the risk of death (HR, 0.73; 95% CI, 0.57-0.93; 

 = .0104). In the durvalumab arm (n = 264), the 24- and 36-month OS rates were 68.0% and 56.5%, respectively. These values were 58.5% and 47.6%, respectively, in the placebo arm (n = 266).

Furthermore, at a median follow-up of 27.6 months (range, 0.0-55.8) in censored patients, durvalumab generated a median PFS of 16.6 months (95% CI, 10.2-28.2) vs 9.2 months (95% CI, 7.4-12.9), respectively. This translated to a 24% reduction in the risk of death or disease progression (HR, 0.76; 95% CI, 0.61-0.95; 

 = .0161), Spigel adds. In the durvalumab arm, the 24- and 36-month OS rates were 48.8% and 46.2%, respectively. These values were 36.1% and 34.2%, respectively, in the placebo arm.

Notably, ADRIATIC also enrolled patients to a third arm, where they received dual checkpoint inhibition with durvalumab plus the CTLA-4 inhibitor tremelimumab-actl (Imjudo), Spigel says. Future data readouts from this trial will include findings from an analysis of the durvalumab/tremelimumab arm vs the placebo arm, although those data are currently blinded, Spigel concludes.

David R. Spigel, MD, discusses findings from the phase 3 ADRIATIC trial in patients with limited-stage small cell lung cancer.

David Spigel, MD, chief scientific officer, director, the Lung Cancer Research Program, principal investigator, Sarah Cannon Research Institute, discusses potential upcoming developments in targeted therapies for non–small cell lung cancer (NSCLC).

Targeted therapies against HER2 and TROP2 have produced recent intriguing data, which could lead to accelerated approval strategies in NSCLC, Spigel says. By the end of 2022, multiple antibody-drug conjugates could become FDA approved for the HER2 and TROP2 populations, depending on the results of ongoing phase 3 trials, Spigel explains.

Over the next few years, data will also mature and read out on several clinical trials involving immunotherapy agents in the neoadjuvant and adjuvant settings, which could also shift the treatment paradigm, Spigel concludes.

David Spigel, MD, discusses potential upcoming developments in targeted therapies for non–small cell lung cancer.


David R. Spigel, MD

Articles

Dr Spigel on Adjuvant Chemotherapy in Stage IA/IIA, Molecularly Higher-Risk NSCLC

Dr Spigel on the Efficacy of Durvalumab Consolidation Therapy in LS-SCLC

Dr. Spigel on Potential Advancements in Targeted Therapy in NSCLC