Adjuvant atezolizumab improves DFS in early-stage NSCLC

In patients with completely resected stage II–IIIA non-small-cell lung cancer (NSCLC) who had previously received adjuvant cisplatin chemotherapy, adjuvant atezolizumab extended disease-free survival (DFS), particularly in those with PD-L1 expression ≥1 percent on tumour cells, interim results of the phase III IMpower010 trial showed.

“Compared with best supportive care, the risk of recurrence, new primary NSCLC, or death was reduced with atezolizumab by 34 percent in patients in the stage II–IIIA population whose tumours expressed PD-L1 on [≥1 percent] of tumour cells, and by 21 percent in all patients in the stage II–IIIA population,” the researchers said.

This multinational, open-label trial included 1,269 adults with completely resected stage IB (tumours ≥4 cm) to IIIA NSCLC*, ECOG performance status 0–1, and with previous exposure to one to four 21-day cycles of adjuvant cisplatin-based chemotherapy** (last dose 3–8 weeks prior). Of these, 1,005 patients (median age 62 years, 67 percent male, 65.6 percent with non-squamous histology, 54.6 percent with PD-L1 expression ≥1 percent of tumour cells) were randomized 1:1 to receive adjuvant intravenous atezolizumab (1,200 mg every 21 days for 16 cycles or 1 year) or best supportive care (observation and regular scans for disease recurrence).

The most common surgery types were lobectomy (78.1 percent), pneumonectomy (15.9 percent), and bilobectomy (5.0 percent), and the most common chemotherapy regimens were cisplatin-pemetrexed (38.3 percent) and cisplatin-vinorelbine (30.1 percent). Eighty-one percent underwent mediastinal lymph node dissection. The median time between surgery and the first randomized treatment was 5.2 months.

 

Improved DFS

After a median 32.8 months of follow-up, there was a 34 percent improvement in investigator-assessed DFS with atezolizumab compared with best supportive care in the subpopulation of patients with stage II–IIIA disease with PD-L1 expression ≥1 percent (median not estimable vs 35.3 months; hazard ratio [HR], 0.66, 95 percent confidence interval [CI], 0.50–0.88; p=0.0039), with 35 and 46 percent of patients, respectively, having DFS events. [WCLC 2021, abstract PL02.05; Lancet 2021;doi:10.1016/S0140-6736(21)02098-5]

There was a 21 percent improvement in DFS with atezolizumab vs best supportive care among all patients with stage II–IIIA disease after a median follow-up of 32.2 months (median 42.3 vs 35.3 months; HR, 0.79, 95 percent CI, 0.64–0.96; p=0.020), with 39 and 45 percent of patients, respectively, experiencing DFS events.

In the overall intention-to-treat (ITT) population (stage IB–IIIA disease), 37 and 43 percent of patients in the atezolizumab and best supportive care groups, respectively, experienced DFS events, though after a median 32.2 months of follow-up, the statistical significance boundary was not crossed (median not estimable vs 37.2 months; HR, 0.81, 95 percent CI, 0.67–0.99; p=0.040).

Exploratory analyses suggested that the DFS benefits with atezolizumab were generally consistent across most subgroups among patients with stage II–IIIA disease with PD-L1 expression ≥1 percent as well as the total stage II–IIIA population. Overall survival data were immature at time of analysis, with 19 and 18 percent of deaths having occurred in the atezolizumab and best supportive care groups, respectively, in the ITT population.

Eleven and 16 percent of patients in the atezolizumab and best supportive care groups, respectively, received subsequent radiotherapy for recurrent or new disease, 5 and 7 percent subsequent surgery, and 20 and 26 percent post-recurrence systemic non-protocol anticancer therapies.

Patients in the atezolizumab group received a median 16 cycles of treatment, with 65 percent of patients completing 16 cycles.

 

Safety profile

Of the 990 patients who were assessed for safety (495 patients in each group), adverse events (AEs) occurred in 93 and 71 percent of atezolizumab and best supportive care recipients, respectively, grade 3–4 AEs in 22 and 12 percent, respectively, and grade 5 AEs in 2 and 1 percent, respectively. Serious AEs occurred in 18 and 8 percent, respectively. Among atezolizumab recipients, 29 and 18 percent experienced AEs that led to dose interruption and treatment discontinuation, respectively.

The most common grade 3–4 AEs with atezolizumab were alanine aminotransferase and aspartate aminotransferase elevations (2 and 1 percent, respectively) and pneumonia (1 percent).

Among atezolizumab recipients, 68 percent experienced treatment-related AEs (TRAEs), with 11 percent experiencing grade 3–4 TRAEs, and 7 percent serious TRAEs. The most common TRAEs in atezolizumab recipients were hypothyroidism, pruritus, and rash (11, 9, and 8 percent, respectively). Four patients experienced grade 5 TRAEs. Immune-mediated AEs occurred in 52 and 9 percent of atezolizumab and best supportive care recipients, respectively, with 8 and 1 percent, respectively, being grade 3–4. The most common immune-mediated AEs were hepatic laboratory abnormalities, rash, and hypothyroidism. Twelve percent of atezolizumab recipients who had immune-mediated AEs required corticosteroid treatment.

 

Another potential treatment for early-stage NSCLC?

“[T]he positive primary endpoint results, along with a safety profile consistent with previous reports and no new safety signals, suggest that atezolizumab after adjuvant chemotherapy might offer a promising treatment option that extends DFS in patients with stage II–IIIA resected early-stage NSCLC, specifically in patients whose tumours express PD-L1 on ≥1 percent of their tumour cells and especially in patients whose tumours express PD-L1 on ≥50 percent of tumour cells [unstratified HR, 0.43],” the researchers pointed out.”

“The results from … IMpower010 now provide another positive outcome with adjuvant treatment in patients with resected stage II–IIIA NSCLC,” they added.

“[T]he improvement in DFS appears to be largely driven by patients with PD-L1 expression on ≥50 percent of tumour cells,” said Assistant Professor Justin Gainor from the Massachusetts General Hospital, Boston, Massachusetts, US, in a commentary. [Lancet 2021;doi:10.1016/S0140-6736(21)02100-0]

As such, the patient population most likely to benefit from adjuvant atezolizumab needs to be ascertained, he said.