The 8 Most Notable Cancer Clinical Trials of 2019

Victoria Stern, MA


December 13, 2019

The laudable progress of expanded treatment options for patients with cancer continued in 2019, with more than a dozen approvals by the US Food and Drug Administration (FDA) for new oncology drugs or new indications for existing drugs. Here is a look at 8 major clinical trials publishing results this year on cancer treatments—including immunotherapy, poly(ADP)ribose polymerase (PARP) inhibitors, and cyclin-dependent kinase (CDK) 4/6 inhibitors—that advanced, and in some cases transformed, patient care.

Immunotherapy at 5 Years: KEYNOTE-001 and CheckMate 067

Not long ago, patients with metastatic non–small cell lung cancer (NSCLC) had bleak survival odds—the likelihood of living 5 years after diagnosis was 5% or less. The 2019 FDA approval of pembrolizumab as a first-line treatment for patients with stage III NSCLC signals just how far we have come.

Results from the phase 1b KEYNOTE-001 trial of pembrolizumab as first-line monotherapy for advanced or metastatic NSCLC highlight its game-changing impact on patient prognosis. Data presented at the 2019 American Society of Clinical Oncology annual meeting demonstrated that close to 25% of patients receiving pembrolizumab who were treatment naive were alive at 5 years.

"[The outcomes] speak to the durability of the treatment benefit and are clinically very important," said Suresh Ramalingam, MD, professor and deputy director of the Winship Cancer Institute of Emory University in Atlanta.

KEYNOTE-001 included 550 patients with no EGFR or ALK gene mutations, 100 of whom were treatment-naive. For patients with tumors with a high expression of programmed cell death ligand 1 (PD-L1 ≥ 50%), survival odds improved: Almost 30% of patients who were treatment naive and 25% of previously treated patients with this PD-L1 status were alive at the 5-year mark. The drug was also generally well tolerated, with immune-related adverse events affecting 17% of patients and pneumonitis—the most serious side effect—occurring in less than 5% of patients.

"This study raises the potential that a treatment might lead to a cure of metastatic lung cancers, which is a paradigm shift for a traditionally 'incurable' illness," said Mark G. Kris, MD, a medical oncologist specializing in lung cancer at Memorial Sloan Kettering Cancer Center in New York City.

Immunotherapies are also transforming survival in melanoma. A recent analysis published in The New England Journal of Medicine reported that more than half of patients (52%) receiving nivolumab plus ipilimumab were alive at 5 years, compared with 44% receiving nivolumab and 26% receiving ipilimumab.

This study expands on initial 2017 results from the CheckMate 067 study, which randomized 945 patients to one of these three immunotherapy regimens. Investigators reported almost 60% of patients in the combination therapy group were alive at 3 years compared with 52% and 34% in the nivolumab and ipilimumab arms, respectively. In fact, in 2018, the National Comprehensive Cancer Network guidelines added nivolumab/ipilimumab as a first-line option for patients with advanced melanoma.

"The original CheckMate 067 study was practice changing, and the 5-year follow-up data are reassuring," said melanoma expert and study investigator Michael Postow, MD, of Memorial Sloan Kettering Cancer Center. "More than half of patients are alive 5 years from the start of treatment with nivolumab plus ipilimumab, which means that with immunotherapy, metastatic melanoma is no longer life limiting in about half of patients."

The next step, Postow said, will be to understand whether combining immunotherapy with BRAF-directed targeted therapies would further improve overall survival. Recent trials have explored triplet therapy combining targeted inhibitors and immunotherapy, but Postow noted that oncologists still require larger studies before they change their treatment practices.

"Combining targeted therapy and immunotherapy is a hot area in melanoma, but we're not at a point yet where patients should receive these triplets based on the available data," Postow said.


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