Atezolizumab Plus Chemotherapy Feasible Before NSCLC Resection

Author: By Lynda Williams, Senior medwireNews Reporter 

medwireNews: Over half of the participants in a phase II trial given atezolizumab and chemotherapy before surgery for early-stage non-small-cell lung cancer (NSCLC) achieved a major pathological response. 

“Our findings suggest that neoadjuvant atezolizumab and chemotherapy could be a potential therapeutic option for patients with resectable non-small-cell lung cancer”, say Naiyer Rizvi, from Columbia University Irving Medical Center in New York, USA, and co-investigators.

The study was open to former or current smokers with a good ECOG performance status and the majority (77%) of the patients had high-risk stage IIIA disease, the researchers explain.

The patients were given atezolizumab 1200 mg and carboplatin to an AUC of 5 on day 1 of a 21-day cycle, alongside nab-paclitaxel 100 mg/m2 on days 1, 8 and 15. Patients who remained free from disease progression after two cycles received a further two cycles before surgery.

“Even though the main concern with neoadjuvant treatment remains the preclusion of surgery due to disease progression, almost all patients in our cohort were able to proceed to surgery, and around 50% of patients had nodal downstaging of disease from N2 stage, thus eliminating the need for postoperative radiotherapy”, the researchers say.

An R0 resection was achieved in 87% of the patients; one patient developed brain metastases and was no longer eligible for surgery, and three patients were found to have inoperable disease during surgery.

After a median of 12.9 months, 57% of patients achieved a major pathological response at time of surgery and 33% a pathological complete response, including six patients with stage IIIA disease. In addition, 63% achieved a RECIST partial response following surgery and 30% stable disease.

Median disease-free survival (DFS) was 17.9 months and median overall survival was not reached, the investigators add.

Post-hoc analysis indicated that PD-L1 expression did not predict pathological response but did identify a trend towards longer DFS with a pathological response, although the investigators emphasize that “any interpretation should […] be made with caution.”

“The treatments were safe and well tolerated with toxic effects consistent with published data”, Naiyer Rizvi et al say.

The most common grade 3–4 treatment-related adverse events were neutropenia (50%), elevated alanine aminotransferase and aspartate aminotransferase (7% each) and thrombocytopenia (7%), and there were no treatment-related deaths.

“Our trial, together with ongoing randomised trials, provides more evidence on the risks and benefits of immunotherapy as a neoadjuvant treatment, and could help to answer questions regarding the optimal duration, best surrogate endpoint, and best predictive biomarkers for treatment”, the team summarises in The Lancet Oncology.

They add: “Pathological response as an early surrogate endpoint for survival is encouraging, and if validated as a biomarker, could shorten the time between trials and approval of therapy by pharmaceutical regulatory authorities, thereby allowing more patients faster access to therapies.” 

Reference  

Shu CA, Gainor JF, Awad MM, et al. Neoadjuvant atezolizumab and chemotherapy in patients with resectable non-small-cell lung cancer: an open-label, multicentre, single-arm, phase 2 trial. Lancet Oncol; Advance online publication 7 May 2020. https://doi.org/10.1016/S1470-2045(20)30140-6.