Immuno-Oncology

It is becoming increasingly clear that PD-1/ PD-L1 and CTLA-4 represent just the tip of the iceberg when it comes to manipulating the immune system to fight cancer, and the number of known checkpoints—and with it the list of potential drug targets—has expanded in recent years.

As clinical experience grows with new agents, combinations, and sequences of therapy, the use of molecular profiling in metastatic melanoma is likely to become an essential means of choosing among treatment options.

Treatment with pembrolizumab reduced the risk of death by 29% compared with docetaxel for patients with PD-L1-positive non–small cell lung cancer.

The European Commission has approved talimogene laherparepvec as a treatment for adult patients with unresectable stage IIIb, IIIc, and IVM1a melanoma that has not spread to the bone, brain, lung, or other viscera.

The FDA has expanded the approval for single-agent pembrolizumab to include the frontline treatment of patients with advanced melanoma regardless of BRAF status.

Raoul S. Concepcion, MD, FACS, discussed novel therapies for treating mCRPC and deciding which patients are appropriate candidates.

Daniel P. Petrylak, MD, professor of medicine at Yale University Cancer Center, discusses the anti–PD-L1 antibody atezolizumab in bladder cancer.

Omid Hamid, MD, Chief, Translational Research and Immunotherapy, Director, Melanoma Therapeutics, The Angeles Clinic, discusses a recent trial investigating the combination of vemurafenib and atezolizumab in melanoma in patients with previously untreated BRAF-positive unresectable or metastatic melanoma.

James Allison, chair of Immunology at the University of Texas MD Anderson Cancer Center, discusses promising data regarding the use of immunotherapies in melanoma. Allison is particularly excited about a trial, presented at the Society of Melanoma Research Congress, which looked at the combination of PD-L1 inhibitors with a BRAF-targeted agent.

The PD-1 inhibitor pembrolizumab had an overall response rate of 12% in PD-L1–positive patients with ER-positive/HER2-negative advanced breast cancer.

Saeed Rafii, MD, PhD, medical director, Sarah Cannon Research Institute United Kingdom, discusses a study evaluating the safety and clinical activity of atezolizumab in combination with nab-paclitaxel in patients with metastatic triple-negative breast cancer (TNBC).

Frontline treatment with the PD-L1 inhibitor atezolizumab combined with nab-paclitaxel showed a confirmed objective response rate of 66.7% in patients with metastatic triple-negative breast cancer.

Treatment with the PD-L1 inhibitor avelumab demonstrated promising overall response rates for patients with PD-L1–positive metastatic breast cancer, particularly for those with triple-negative disease.

Jesus San Miguel, MD, PhD, professor of Hematology, medical director of the Clínica Universidad de Navarra, Universidad de Navarra, Pamplona, Spain, discusses the Keynote-023 study, which examined pembrolizumab in combination with lenalidomide and low-dose dexamethasone in patients with relapsed/refractory multiple myeloma.

The addition of pembrolizumab to an established multiple myeloma regimen elicited responses in 76% of 17 patients with relapsed/refractory disease.

Lawrence Fong, MD, Professor, Department of Medicine (Hematology/Oncology), University of California San Francisco, discusses the importance of educating oncologists on the side effects of immunotherapies.

Phase Ib/II research has shown promise for adoptive cellular therapy combined with ipilimumab in patients with advanced sarcomas.

Genetically engineered T cells eradicated multiple myeloma cells in a patient with advanced disease, suggesting the potential to cure the condition.

Tara C. Mitchell, MD, Assistant Professor of Medicine at the Hospital of the University of Pennsylvania, discuses preliminary results from a phase I/11 study of epacadostat in combination with pembrolizumab.

As the class of agents targeting the PD-1/PD-L1 pathway expands in non–small cell lung cancer, so does the potential population of patients who would be candidates for the groundbreaking immunotherapy.

Suresh Ramalingam, MD, discusses the evolving role of checkpoint inhibitors in lung cancer and what challenges still remain.