Nivolumab Still Has Edge on Chemo After 4 Years in Advanced NSCLC

By Reuters Staff

September 03, 2019

NEW YORK (Reuters Health) - Patients with advanced non-small-cell lung cancer (NSCLC) who are treated with the anti-PD-1 antibody nivolumab continue to have better survival than those given docetaxel after four years, according to pooled data from four CheckMate trials.

In the two randomized trials, CheckMate 017 and 057, four-year overall survival was 14% in patients on nivolumab versus 5% in those on docetaxel, researchers report in The Lancet Oncology, online August 14.

Prior to the advent of immunotherapy as a second-line treatment for advanced NSCLC, five-year survival of patients with metastatic lung cancer was about 5%.

Across the four studies, the 664 patients treated with nivolumab had a median overall survival of 10.3 months. In CheckMate 003, the study with the longest follow-up, six-year overall survival was 15%, report Dr. Scott J. Antonia from Duke Cancer Institute, in Durham, North Carolina.

The estimated four-year overall survival was higher in patients with at least 1% PD-L1 expression (19%) than in patients with less than 1% PD-L1 expression (11%), but overall survival did not differ significantly between patients with squamous and non-squamous tumor histology.

The estimated four-year progression-free survival was 8% overall and was also higher in patients with at least 1% PD-L1 expression.

Among the 122 patients with a complete or partial response to nivolumab, the median duration of response was 19.1 months. The median overall survival from time of response was 63.2 months, and the estimated four-year overall survival was 53%.

Long-term safety data pooled from all four studies revealed no new safety signals. About 10% of patients experienced serious treatment-related adverse events, and 9% of patients experienced treatment-related adverse events that led to discontinuation of nivolumab.

Pneumonitis was the most frequent serious treatment-related adverse event, occurring in 3% of patients. The most common treatment-related adverse events of potentially immune-related etiology were skin reactions, with an incidence of 38.6 per 100 person-years of nivolumab exposure.

"Our analyses provide evidence that response and disease control with nivolumab strongly benefit long-term survival, even after progression," the researchers conclude. "Additional analyses assessing the effects of various factors on long-term survival with immunotherapy versus chemotherapy are planned."

"A remaining question is the optimal duration of immune checkpoint inhibitor treatment for patients with objective response," write Dr. Pierre-Jean Souquet and Dr. Sebastien Couraud from Institut de Cancerologie des Hospices Civils de Lyon, France, in a related editorial. "Several trials, including IFCT-1701 DICIPLE (NCT03469960), are currently underway to offer answers to these questions."

"Now that a combination of chemotherapy and immunotherapy is becoming the standard first-line treatment for all histologies and for all PD-L1 statuses, it is reasonable to expect greatly improved outcomes with an increasing proportion of patients alive 5 years after diagnosis," they conclude. "The horizon might still be far, but it appears that the tide has turned."

Bristol-Myers Squibb funded the study, employed three of the authors and had various relationships with several others and with both authors of the related editorial.


Lancet Oncol 2019.