Brian Mitzman, MD, FACS, FCCP, assistant professor, Division of Cardiothoracic Surgery, the University of Utah and Huntsman Cancer Institute, discusses the use of adjuvant atezolizumab (Tecentriq) following platinum-based chemotherapy in patients with resectable non–small cell lung cancer (NSCLC).

In October 2021, the FDA approved atezolizumab for use as an adjuvant treatment following resection and platinum-based chemotherapy in patients with stage II to IIIA NSCLC whose tumors have PD-L1 expression on 1% or more of tumor cells. The regulatory decision was based on data from the phase 3 IMPOWER 010 trial (NCT02486718). Patients were required to undergo resection and receive adjuvant chemotherapy before being randomly assigned to atezolizumab or best supportive care. Atezolizumab was given once every 3 weeks for 16 cycles.

Findings that supported the approval showed that the median disease-free survival (DFS) was not yet reached (95% CI, 36.1 months–not evaluable [NE]) for patients receiving atezolizumab, compared with 35.3 months (95% CI, 29.0-NE) for patients receiving best supportive care (HR, 0.66; 95% CI, 0.50-0.88; 

In an interim analysis for overall survival (OS)

, patients who had a PD-L1 expression of at least 1% experienced a 5-year OS rate of 76.8% in the atezolizumab arm, compared with 67.5% in the best supportive care arm.

Additionally, a post-hoc subgroup analysis showed that in the all-randomized stage II to IIIA population with PD-L1 expression on at least 50% of tumor cells, atezolizumab elicited a DFS benefit in patients with 

aberrations (HR, 0.43; 95% CI, 0.27-0.68) and those without those aberrations (HR, 0.43; 95% CI, 0.26-0.71).

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Brian Mitzman, MD, FACS, FCCP, discusses the use of adjuvant atezolizumab following platinum-based chemotherapy in patients with resectable non–small cell lung cancer.

Dr Mitzman on the Use of Adjuvant Atezolizumab After Chemotherapy in Resectable NSCLC

Brian Mitzman, MD, FACS, FCCP, assistant professor, Division of Cardiothoracic Surgery, the University of Utah Huntsman Cancer Institute, discusses the emergence of immunotherapy as a treatment option for patients with early-stage non–small cell lung cancer (NSCLC).

Until recently, the standard of care for patients with stage II or early stage III NSCLC involved resection followed by chemotherapy. However, data from recent clinical trials evaluating immunotherapy in this patient population have paved the way for novel treatment options for patients with early-stage NSCLC, Mitzman says.

the FDA approved nivolumab (Opdivo) plus platinum-doublet chemotherapy in the neoadjuvant setting

 for adult patients with resectable NSCLC, based on data from the phase 3 CheckMate 816 trial (NCT02998528) trial. Findings showed that nivolumab plus chemotherapy elicited a median event-free survival of 31.6 months (95% CI, 30.2–not reached [NR]) vs 20.8 months (95% CI, 14.0-26.7) with chemotherapy alone (HR, 0.63; 95% CI, 0.45-0.87; 

Data from the phase 3 IMpower010 study (NCT02486718) supported 

the FDA approval in October 2021 of atezolizumab (Tecentriq) for use as an adjuvant treatment following resection and platinum-based chemotherapy

in patients with stage II to IIIA NSCLC whose tumors have PD-L1 expression on 1% or more of tumor cells. Results from this study demonstrated that the median disease-free survival (DFS) was NR (95% CI, 36.1–not evaluable [NE]) in patients with stage IB through stage IIIA NSCLC in the atezolizumab arm vs 35.3 months (95% CI: 29.0–NE) for those in best supportive care arm (HR, 0.66; 95% CI, 0.50-0.88; 

Finally, in January 2023, the FDA approved pembrolizumab (Keytruda) as an adjuvant treatment following resection and platinum-based chemotherapy for patients with stage IB (T2a ≥4 cm), II, or IIIA NSCLC, based on data from the phase 3 KEYNOTE-091 trial (NCT02504372). Findings from this study showed that patients in the pembrolizumab arm experienced a median DFS of 58.7 months (95% CI, 39.2-NR) compared with 34.9 months (95% CI, 28.6-NR) for those in the placebo arm (HR, 0.73; 95% CI, 0.60-0.89).

Within his clinical practice, the approval of neoadjuvant nivolumab plus chemotherapy has had the most impact, Mitzman concludes.

Brian Mitzman, MD, FACS, FCCP, discusses the emergence of immunotherapy as a treatment option for patients with early-stage non–small cell lung cancer.

Dr Mitzman on the Emergence of Immunotherapy in Early-Stage NSCLC 

Brian Mitzman, MD, FACS, FCCP, assistant professor, Division of Cardiothoracic Surgery, the University of Utah and Huntsman Cancer Institute, discusses findings from the phase 3 CheckMate 816 trial (NCT02998528) in patients with resectable non–small cell lung cancer (NSCLC).

CheckMate 816 enrolled patients with stage IB to IIIA NSCLC and randomized them to receive either nivolumab (Opdivo) plus platinum-based chemotherapy or platinum-based chemotherapy alone every 3 weeks for 3 cycles, followed by surgery, Mitzman says. After surgery, patients could receive adjuvant chemotherapy at their treating physician’s discretion, Mitzman notes.

This trial’s coprimary end points were event-free survival (EFS) and pathologic complete response (pCR), Mitzman explains. Patients in the nivolumab arm achieved a median EFS of 31.6 months vs 20.8 months in the chemotherapy alone arm, with a hazard ratio of 0.63, Mitzman says. The 2-year EFS rates were 63.8% in the nivolumab arm compared with 45.3% in the chemotherapy alone arm, Mitzman notes. These findings were consistent across most patient subgroups, although the patients who benefitted the most were those with stage IIIA disease, PD-L1 expression of at least 1%, and nonsquamous disease, Mitzman explains. In patients with stage IIIA disease, the median EFS was 31.6 months in the nivolumab arm vs 15.7 months in the chemotherapy alone arm. In patients with positive PD-L1 expression, the median EFS was not reached (NR) in patients who received nivolumab vs 21.1 months in patients who received chemotherapy alone. In patients with nonsquamous disease, the median EFS was NR in the nivolumab arm vs 19.6 months in the chemotherapy alone arm.

Regarding pCR, treatment with nivolumab plus chemotherapy led to a pCR rate of 24.0% vs 2.2% with chemotherapy alone, with an odds ratio of 13.94, Mitzman emphasizes. This benefit was demonstrated across all patient subgroups, regardless of PD-L1 expression, disease stage, and histology, Mitzman says. These findings support the hypothesis that pCR estimates long-term response, Mitzman concludes.

Brian Mitzman, MD, FACS, FCCP, discusses findings from the phase 3 CheckMate 816 trial in patients with resectable non–small cell lung cancer. 

Brian Mitzman, MD, FACS, FCCP

Articles

Dr Mitzman on the Use of Adjuvant Atezolizumab After Chemotherapy in Resectable NSCLC

Dr Mitzman on the Emergence of Immunotherapy in Early-Stage NSCLC

Dr. Mitzman on Neoadjuvant Nivolumab Plus Chemotherapy in NSCLC