ASCO Annual Meeting

ASCO Annual Meeting

June 04, 2019
2 min read

Neoadjuvant atezolizumab shows promise in non-small cell lung cancer

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David J. Kwiatkowski, MD, PhD
David J. Kwiatkowski

CHICAGO — Neoadjuvant atezolizumab induced sustained responses in patients with operable non-small cell lung cancer, according to results from an interim analysis of the LCMC3 trial presented at ASCO Annual Meeting.

The regimen also appeared safe and did not delay surgery.

“Immune checkpoint therapy is included as a standard of care for patients with advanced lung cancer, and this study suggests that there may also be a benefit in early-stage operable disease,” David J. Kwiatkowski, MD, PhD, senior physician at Brigham and Women’s Cancer Center and Dana-Farber Cancer Institute, said during the presentation.

Results from an interim safety analysis of the ongoing LCMC3 trial, presented during last year’s ASCO Annual Meeting, demonstrated preliminary safety and efficacy of atezolizumab (Tecentriq, Genentech), a PD-L1 inhibitor, before resection among 37 patients with potentially operable NSCLC.

For the current interim analysis, 101 patients (median age, 65 years; 47% men) with surgically resectable stage Ib to stage IIIb NSCLC received two cycles of 1,200 mg atezolizumab; 89% underwent surgical exploration for resection.

Major pathologic response, defined as no more than 10% viable tumor cells, served as the primary endpoint. Secondary endpoints included DFS and OS.

Among 90 patients in the intended surgery population, six (7%) achieved partial response and 80 (89%) had stable disease. In the primary efficacy population of 77 patients, 15 (19% (95% CI, 11-30) achieved major pathologic response, four (5%) achieved pathologic complete response and 38 (49%) had pathologic regression.

Researchers observed a significant association between pathologic regression and change in tumor lesion size (P < .001).

Major pathologic response occurred regardless of PD-L1 expression, with major pathologic response observed among patients with high levels of PD-L1 expression (greater than 80%) by PD-L1 IHC 22C3 pharmDx (Dako), and among some patients without PD-L1 expression, according to Kwiatkowski.

Eleven percent of patients with a tumor proportion score of less than 50, and 35% of patients with a tumor proportion score greater than 50, achieved major pathologic response (P = .04).

Results of exome sequencing among 47 patients showed a median tumor mutational burden of 10.3 (range, 1.5-46.5) , with no differences among those with major pathologic response compared with those without major pathologic response.

Researchers also did not observe any significant associations between gene alterations and major pathologic response.

Investigators observed one cardiac death after resection, and one death due to disease progression. There were 29 grade 3 or higher adverse events, of which 6% were treatment-related.


“The efficacy interim analysis passed its futility boundary and study enrollment continues, with 151 of the 180 planned patients enrolled as of May 6,” Kwiatkowski said. “The placebo-controlled phase 3 [IMpower030] study of atezolizumab combined with platinum-based chemotherapy is currently ongoing.” – by Jennifer Southall


Kwiatkowski DJ, et al. Abstract 8503. Presented at: ASCO Annual Meeting; May 31-June 4, 2019; Chicago.

Disclosures: Kwiatkowski reports consultant/advisory roles with Genentech/Roche and Novartis; and research funding from AADi, Genentech/Roche and Revolution Medicines. Please see the abstract for all other authors’ relevant financial disclosures.