Immune Therapy overtakes Chemo in NSCLC- Nivolumab increases survival in Squamous cell cancer

By Dr Deepu

Patients with previously treated advanced or metastatic squamous non-small cell lung cancer (NSCLC) had improved survival with an immunotherapeutic drug than with chemotherapy, according to updated results from a randomized trial.

Twice as many patients treated with nivolumab (Opdivo) remained alive at 18 months as compared with those treated with docetaxel, and six times as many patients were alive without progression at 18 months with nivolumab as compared with the chemotherapy standard for NSCLC.

Median overall survival was 9.2 months with nivolumab and 6.0 months with docetaxel,  reported here at the World Conference on Lung Cancer.

A second trial involving patients with treatment-refractory squamous NSCLC similar improvement in outcomes with nivolumab versus docetaxel.

Accounting for about 20% of NSCLC cases, patients with squamous-cell NSCLC represent a poor-prognosis minority who have few options after progression or failure of first-line platinum-based chemotherapy. Second-line docetaxel is associated with modest clinical activity (median overall survival of 5 to 8 months, objective response rate of 3% to 9%) and significant toxicity.

Nivolumab, a fully human PD-1 immune checkpoint inhibitor antibody, has demonstrated activity in both squamous and nonsquamous NSCLC and received FDA approval earlier this year for patients with squamous NSCLC that had progressed during or after platinum-based chemotherapy.

At the American Society of Clinical Oncology meeting in June, investigators reported preliminary results from a randomized comparison of nivolumab and docetaxel in patients with previously treated advanced/metastatic squamous NSCLC. At that point the data showed a 1-year survival of 42% with nivolumab versus 24% with docetaxel, and a median PFS of 9.2 vs 6.0 months, also in favor of nivolumab.

The anti-PD-1 antibody maintained superiority across all prespecified subgroups, including age, geographic location, performance status, and prior therapy. Moreover, the survival benefit persisted across all categories of PD-L1 expression: positive, negative, and not quantifiable.

Patients treated with nivolumab had substantially fewer treatment-related adverse events, including any adverse events (59% vs 87%), grade 3-5 adverse events (8% vs 58%) and adverse events leading to discontinuation (5% vs 10%). No treatment-related deaths occurred in the nivolumab arm as compared with a 2% rate in the docetaxel group.

Similar superiority for nivolumab emerged from the phase II, single-arm CheckMate 063trial, which involved 117 patients with advanced/metastatic squamous NSCLC that had progressed during or after platinum-based chemotherapy plus at least one other systemic regimen.

The trial had a primary endpoint of independently reviewed and confirmed objective response. The data showed an overall response rate of 15% (17 of 117), three fourths of which are ongoing said Horn. The median time to response was 3.3 months, and the median duration of response has yet to be reached (range of 1.9 to 11.5 months). The cohort had a median PFS of 1.9 months and a 1-year PFS of 20%.

Responses were observed across all predefined subgroups, including age, number of prior therapies, performance status, and level of PD-L1 expression.

After a median follow-up of 8 months, the cohort had a median overall survival of 8.1 months, a 1-year overall survival of 39%, and 18-month survival of 27%. The updated data remained consistent with the primary analysis in July 2014, which showed a median overall survival of 8.2 months and 1-year overall survival of 41%.

Overall, 17% of the patients had grade 3/4 adverse events, the most common being gastrointestinal and pulmonary in nature (3% each). Horn noted that no new grade 3/4 adverse events occurred from the initial assessment through the updated analysis in June 2015.