Checkpoint Inhibitors Changing Landscape for Advanced Solid Tumors

Published: Tuesday, Nov 29, 2016
Dean F. Bajorin, MD

Dean F. Bajorin, MD

Immunotherapy continues to be one of the fastest-evolving fields in oncology. In recent years, numerous immunotherapies have shown good efficacy, safety, and durability across many tumor types, including some advanced solid tumors that have not seen meaningful treatment developments in decades.

During an OncLive Peer Exchange panel titled “Immunotherapy Use in Advanced Solid Tumors,” recent developments in this field were described as “historic,” heralding a dramatic shift in the cancer treatment paradigm. “Everything we’ve done up until a few years ago has really been to fight the cancer, usually with chemotherapy, but now we have tools that help an individual fight his or her own tumor,” said Dean F. Bajorin, MD.

During the Peer Exchange program, the panelists provided an overview on how immunotherapies are changing the treatment landscape for melanoma, lung, kidney, bladder, and head and neck cancers. Much of the discussion focused on immune checkpoint inhibitors, including PD-1, PD-L1, and CTLA-4 inhibitors, which have generated some of the greatest developments in this field to date.

As these new therapies are integrated into treatment paradigms, clinicians are raising many questions about managing associated toxicities that patients experience, said Mark A. Socinski, MD, who served as moderator for the program. The new agents have “a different spectrum of toxicity,” he said.

“I field many phone calls on a weekly basis from our regional referring community oncologists about how to handle toxicities,” Socinski said. “There’s a huge learning curve in terms of recognition and treatment.”


Melanoma set the stage for immunotherapies, and several agents have been approved by the FDA for these patients, including the PD-1 inhibitors nivolumab (Opdivo) and pembrolizumab (Keytruda), the CTLA-4 inhibitor ipilimumab (Yervoy), and a combination of ipilimumab and nivolumab. “These agents are increasingly be- coming the standard of care for melanoma,” said Howard L. Kaufman, MD. Because these agents got their start in melanoma, the follow-up data are the longest for these patients and the results have been unprecedented.

In a recently presented long-term follow-up study of patients with metastatic melanoma treated with nivolumab for up to 2 years, 34% were alive 5 years after starting treatment, which is slightly more than double the historical 5-year survival rate of 16.6%.1 “If you get a good response with these drugs, it translates to real durability and response,” said Kaufman.

Lung Cancer

In 2015, nivolumab and pembrolizumab were both approved for squamous and nonsquamous non–small cell lung cancer (NSCLC). For squamous histology, where advances have been slow to come, patients had an improvement in median overall survival (OS) from 6 months with docetaxel to 9.2 months for nivolumab.2 Additionally, 18-month survival was improved from 13% with docetaxel to 28% with nivolumab.2 “What patients want is a chance at being alive many months or years down the road...this was a very meaningful improvement,” said Jared M. Weiss, MD.

In patients with nonsquamous histology, the median OS improved from 9.4 months with docetaxel to 12.2 months with nivolumab, and 1-year survival increased from 39% to 51%.3 Pembrolizumab showed similar results, but patients were selected based on their PD-L1 status and not on their histology, as in the nivolumab trials; however, when PD-L1 staining of nivolumab-treated patients was retrospectively examined, “there was no class of PD-L1 status that did not bene t,” said Weiss.

Initially, both drugs were approved for patients with progressive disease after the failure of other therapies but that picture changed dramatically in late October when the FDA granted pembrolizumab a frontline indication for patients with metastatic NSCLC whose tumors show ≥50% PD- L1 expression based on an FDA-approved test and who do not harbor EGFR or ALK aberrations.

The agency’s ruling came just weeks after research presented at the 2016 ESMO Congress demonstrated that single-agent pembrolizumab reduced the risk of death by 40% compared with doublet chemotherapy for previously untreated patients with NSCLC with PD-L1 expression on ≥50% of cells, called a tumor proportion score.4

In the progressive-disease setting, pembrolizumab has a companion diagnostic that requires at least 1% staining with the 22C3 antibody for the drug to be administered, whereas nivolumab has a complementary diagnostic but can be given without knowing PD-L1 status, noted Weiss.

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