Lung cancer

Adjuvant immunotherapy the new standard of care in patients with resected, early-stage NSCLC?


Patients with resected, early-stage non-small cell lung cancer (NSCLC) may benefit from adjuvant immunotherapy following adjuvant chemotherapy, according to new findings from a trial of atezolizumab.

Presented at the European Society for Medical Oncology (ESMO) virtual Congress 2021, the results from the IMpower010 phase 3 RCT showed that  atezolizumab extended disease-free survival in patients with stage II–IIIA resected early-stage NSCLC.

The benefits were most evident for patients whose tumours expressed PD-L1 on 50% or more of tumour cells, the study investigators said.

The IMpower010 trial enrolled 1280 patients across 231 sites, who received up to four cycles of adjuvant chemotherapy. Of these, 1005 patients were then randomized in a 1:1 ratio to receive up to one year of immune-based therapy, atezolizumab, or best supportive care.

After a median follow up of 32 months, disease relapse was observed in 29% of resected NSCLC patients with stage II and IIIA and tumours positive for PD-L1 expression treated with atezolizumab compared with 44.7% in the control arm of the study.

The exploratory analysis also showed disease-free survival at two years in 74.6% of these patients who were treated with immunotherapy, versus 61% in patients receiving best supportive care.

Compared with best supportive care, the risk of recurrence, new primary NSCLC, or death was reduced by 21% in all patients with stage II–IIIA disease treated with atezolizumab regardless of PD-L1 expression (HR 0·79; 0·64–0·96; p=0·020), and by 34% in patients in the stage II–IIIA population whose tumours expressed PD-L1 on 1% or more of tumour cells (hazard ratio [HR] 0·66; 95% CI 0·50–0·88; p=0·0039).

Post-hoc analysis suggested the improvement in disease-free survival was largely driven by patients with PD-L1 expression on 50% or more of tumour cells (HR 0·43; 95% CI 0·27–0·68). In patients with PD-L1 expression on 1–49% of tumour cells, the disease-free survival HR was only 0·87 (0·60–1·26).

Immune-related adverse events occurred with atezolizumab at the same rate as reported in previous studies, with the most common being hepatic laboratory abnormalities, rash, and hypothyroidism.

Most immune-mediated adverse events were mild grade 1 or 2 events that were manageable with treatment interruption or appropriate treatment such as steroids, according to results published simultaneously in The Lancet.

The results were hailed as “an important landmark in thoracic oncology” in  an accompanying commentary, which said that as with osimertinib in the recent ADAURA trial, the primary endpoint of disease-free survival. Could be accepted as a clinically meaningful surrogate for overall survival.

Dr Justin Gainor of the Massachusetts General Hospital, Boston, said the key question was which subgroups of patients would benefit most from the adjuvant immunotherapy, with other studies suggesting those with higher levels of PD-L1.

“IMpower010 represents an important step forward. In my view, adjuvant atezolizumab should be a new standard of care for patients with surgically resected, PD-L1-positive stage II–IIIA NSCLC after completion of adjuvant chemotherapy, with particular emphasis on those patients with PD-L1 expression on 50% or more tumour cells,” he concluded.

Speaking at the ESMO meeting, the study investigators said patients with early-stage NSCLC were at high-risk of disease relapse despite adjuvant chemotherapy, and therefore improving disease-free survival was an unmet and critical clinical need.

“Considering our data, atezolizumab is certainly stepping up as more effective therapy for this patient population,” said Dr Enriqueta Felip, Principal Investigator of VHIO’s Thoracic Tumors & Head and Neck Group, and Head of the Thoracic Cancer Unit at the Vall d’Hebron University Hospital, Barcelona.

Also commenting at ESMO, Dr Antonio Passaro from the European Institute of Oncology, Milan, said it was reassuring that, although there was no clear difference in the pattern of relapse between the arms, the sites of relapse were consistent with what would be expected to in this setting.

“The updated results from IMpower010 support the practice-changing outcomes from the interim DFS analysis and confirm the role of atezolizumab after adjuvant chemotherapy in patients with radically resected, early-stage NSCLC,” he said.

The study was funded by Roche.

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