Durable Response with Immunotherapy Combos in NSCLC with Brain Metastases

Combination nivolumab (Opdivo) and ipilimumab (Yervoy) with chemotherapy offered a durable survival benefit versus chemotherapy alone in advanced non-small cell lung cancer (NSCLC) with brain metastases, according to an analysis of the CheckMate 9LA trial.

Dual immunotherapy plus chemotherapy extended progression-free survival (PFS) to a median of 10.4 months versus a PFS of 4.1 months in patients who received only chemotherapy, reported David Carbone, MD, PhD, of The Ohio State University Comprehensive Cancer Center in Columbus, at the virtual World Conference on Lung Cancer (WCLC).

“These data further support the use of nivolumab plus ipilimumab plus chemotherapy as an efficacious first-line treatment option in patients with advanced non-small-cell lung cancer, including those with brain metastases,” he stated.

In a separate WCLC study, Ernest Nadal, MD, PhD, of the Catalan Cancer Institute in Barcelona, and colleagues reported that atezolizumab (Tecentriq) plus carboplatin and pemetrexed proved safe and efficacious in 40 patients with advanced NSCLC with untreated brain metastases.

WCLC discussant Charu Aggarwal, MD, MPH, of the University of Pennsylvania in Philadelphia, noted that “Patients with brain metastases tend to do well will the addition of immunotherapy-based therapy. The outcomes are similar to patients without brain metastases.”

“Patients with asymptomatic brain metastases can be safely treated with immunotherapy,” she stated, although cautioned that “the selection of patients is key.”

Of the more than 600 patients in the CheckMate 9LA study, 101 had documented baseline brain metastases. Among those patients, 51 were assigned to receive immunotherapy-chemotherapy while 50 got chemotherapy alone. At 12 months, 36% of the former group achieved an objective response versus 8% of the latter group, Carbone reported. Overall, 33% of the immunotherapy-chemotherapy patients responded to treatment versus 21% of those on chemotherapy alone.

Carbone also reported that the median duration of response among the patients on immunotherapy-chemotherapy was 22.3 months versus 18.9 months for patients on chemotherapy only.

As for adverse events (AE), any-grade neurological treatment-related AEs occurred in 22% of the immunotherapy-chemotherapy group and 10% of the chemotherapy group; most were grade 1/2. No new safety signals were seen, the authors added.

In the phase II ATEZO-BRAIN study, conducted at 11 cancer centers in Spain, eligible patients had untreated stage IV non-squamous NSCLC with brain metastases and were EGFR/ALK negative. Patients had to have an ECOG 0-1 performance status, and have measurable lesions systemically and in the brain.

At a median follow-up of 17.3 months, the combination led to a median systemic PFS of 8.9 months (95% CI 6.7-13.8), while the median intracranial PFS was 6.9 months (95% CI 4.7-12.1). The 18-month PFS rate was 24.9% systemically and 10.4% intracranially, Nadal’s group reported. They also found that the 12-week PFS rate was 60%, which exceeded the expected rate of 50%.

The intracranial ORR was 40%, and 10% of the patients achieved a complete response, while 47.5% experienced stable disease.

The grade 3/4 toxicity rate was 27.5%, while most treatment-related AEs were grade 1/2 (most commonly fatigue), and no fatal treatment-related AEs occurred.

Finally, median overall survival (OS) was 13.6 months (95% CI 9.7-not reached) and the 2-year OS rate was 32%, according to Nadal and colleagues.

‘This combination can result in clinical benefit in terms of overall survival in this population, with 32% of patients alive at 2 years,” Nadal emphasized.