The following article features coverage from the American Society of Clinical Oncology 2019 meeting. Click here to read more of Cancer Therapy Advisor‘s conference coverage.

Interim efficacy results of a large, multicenter study of patients with resectable non-small cell lung cancer (NSCLC) treated with the anti-programmed cell death-ligand 1 (PD-L1) antibody, atezolizumab, in the neoadjuvant setting showed that nearly 30% of those with PD-L1–positive disease achieved a major pathologic response. The findings from this study were presented at the 2019 American Society of Clinical Oncology (ASCO) Annual Meeting.1

Although results from pilot studies involving relatively small numbers of patients have provided support for the safety and feasibility of preoperative immune checkpoint inhibitor therapy for patients with resectable NSCLC,larger studies are needed to more fully address the clinical outcomes and biomarkers of response for patients receiving these treatments.2

In this ongoing, single-arm, phase 2 study (ClinicalTrials.gov Identifier: NCT02927301), patients with stage IB, stage II, stage IIIA, or selected stage IIIB disease were treated with atezolizumab at a dose of 1200 mg on days 1 and 22 prior to undergoing resection on day 40 plus or minus 10. Specimens of tumor (with or without nodal biopsy) and peripheral blood were obtained prior to treatment with immune checkpoint inhibitor therapy, and also at the time of surgery.

The primary end point of the study is the percentage of patients achieving a major pathological response (MPR), defined as 10% or fewer viable tumor cells in the resection specimen. Secondary study end points include safety, overall response rate per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 at approximately 10 weeks following surgery, and MPR in biomarker-defined subsets, such as patients with PD-L1–positive and PD-L1–negative tumors.

Clinicopathologic characteristics of the 101 patients included in this analysis were as follows:  median age of 65 years; nonsquamous disease in 65%; 90% were current/former smokers; and clinical stage IIIA/B disease in 46% of patients. In addition, 54% of the tumors were negative for PD-L1 by immunohistochemistry.

Eighty-four patients (83%) underwent a full resection following treatment with atezolizumab. However, all patients with stage I or stage II disease at study entry underwent surgical resection.

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When the 7 patients with EGFR or ALK driver mutations were excluded, the MPR rate in the remaining  patients in the surgery group was 19%, including 4 pathological complete responses (5%). By RECIST v1.1, the rates of partial response, stable disease, and progressive disease were 7%, 89%, and 4%, respectively, in this group.

When MPR rates were evaluated in specific biomarker-related subsets depending on the presence or absence of PD-L1 expression, responses occurred in both tumor PD-L1–positive and PD-L1–negative patient groups, although there was some correlated between higher MPR rates and higher expression of PD-L1 (P =.040). However, MPR was not correlated with tumor mutational burden or associated with the presence of specific gene mutations.

No new safety signals for patients receiving immune checkpoint inhibitor therapy were observed in this study. Regarding grade 3 or higher treatment-related adverse events, pneumonitis, nasal congestion, lymphoctopenia, and anemia occurred in 3, 1, 1, and 1 patient(s), respectively.

In his closing remarks, the presenter of the study commented that a phase 3, placebo-controlled trial of neoadjvuant atezolizumab in combination with chemotherapy in resectable NSCLC is ongoing (ClinicalTrials.gov Identifier: NCT03456063).

Read more of Cancer Therapy Advisor‘s coverage of ASCO’s annual meeting by visiting the conference page.

References

  1. Kwiatkowski DJ, Rusch VW, Chaft JE, et al. Neoadjuvant atezolizumab in resectable non-small cell lung cancer (NSCLC): Interim analysis and biomarker data from a multicenter study (LCMC3). Presented at: 2019 American Association of Clinical Oncology (ASCO) Annual Meeting; May 31-June 3, 2019; Chicago, IL. Abstract 8503.
  2. Forde PMChaft JESmith KN, et al. Neoadjuvant PD-1 blockade in resectable lung cancer. N Engl J Med. 2018;378(21):1976-1986.