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ELCC 2019: Does Maintenance Immunotherapy Improve Survival in Patients With Advanced SCLC?

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Key Points

  • Overall survival was not significantly prolonged with nivolumab plus ipilimumab vs placebo.
  • Overall survival was also not prolonged for nivolumab alone vs placebo, although not formally tested due to statistical hierarchy.
  • Adverse event rates were 86% with nivolumab plus ipilimumab, 61% with nivolumab, and 50% with placebo.

Maintenance immunotherapy did not improve survival in patients with extensive-stage small cell lung cancer (SCLC), according to late-breaking results from the CheckMate 451 study presented today by Owonikoko et al at the European Lung Cancer Congress 2019 (Abstract LBA1_PR).

Around 60% to 70% of patients with SCLC have extensive disease at the time of diagnosis, meaning it has spread beyond a single lung and nearby lymph nodes and cannot be treated with radiotherapy. Most patients respond to chemotherapy, but the duration of the response is usually short. The standard approach after chemotherapy is to wait until the tumor grows before intervening. This study examined whether acting earlier by giving maintenance immunotherapy after successful chemotherapy would improve overall survival.

Methods

The study enrolled 834 patients with extensive-stage SCLC whose cancer did not progress after 4 cycles of chemotherapy. Patients were randomly assigned in a 1:1:1 ratio to combination immunotherapy with nivolumab and ipilimumab, nivolumab alone, or placebo. Baseline characterisitics were balanced between all three treatment arms.

Patients were treated for 2 years or until cancer progression, death, or unacceptable toxicity. The primary endpoint was overall survival for the combination of nivolumab plus ipilimumab vs placebo.

Results

The minimum study follow-up was 9 months. Compared to placebo, overall survival was not significantly prolonged with combination immunotherapy (hazard ratio [HR] = 0.92; 95% confidence interval [CI] = 0.75–1.12; P = .3693). Overall survival was also not prolonged for nivolumab alone vs placebo (HR = 0.84; 95% CI = 0.69–1.02), although that comparison was not formally tested due to statistical hierarchy. Progression-free survival hazard ratios vs placebo were 0.72 (0.60–0.87) for nivolumab plus ipilimumab and 0.67 (0.56–0.81) for nivolumab alone. 

Adverse event rates were 86% with nivolumab plus ipilimumab, 61% with nivolumab, and 50% with placebo. Rates of discontinuation due to toxicity were 31% with combination immunotherapy, 9% with nivolumab, and less than 1% with placebo.

Treatment-related deaths occurred in 7 (2.5%) patients on nivolumab plus ipilimumab, 1 patient on nivolumab, and 1 patient on placebo. Study author Taofeek Owonikoko, MD, PhD, MSCR, Co-Chair of the Clinical and Translational Review Committee, Winship Cancer Institute of Emory University, Atlanta, said the finding was “a big disappointment.”

He added, “There was some indication that compared to placebo, it took longer for the cancer to progress in patients who received either combination immunotherapy or nivolumab alone. This was not the primary endpoint of the study, so we cannot make definitive conclusions, but it shows that this strategy could be promising, especially in patients who are responsive to immunotherapy. The challenge will be how to select and identify those patients since patients who began maintenance therapy sooner after completion of chemotherapy did appear to derive greater benefit.”

Disclosure: The study authors’ full disclosures can be found on ELCC’s Conference Calendar.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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