For decades, there has been precious little good news in the arena of lung cancer. But the tide is turning as new screening guidelines encourage low-dose CT screening scans for those most at risk for lung cancer and new therapies for those whom receive the dreaded positive diagnosis break on the shores of hope.
Lou Fehrenbacher, MD, medical director of Kaiser Permanente Oncology Clinical Trials and oncologist with the Kaiser Permanente Vallejo (Calif.) Medical Center, said a new category of lung cancer drugs, immune stimulating medications called “immune checkpoint inhibitors,” represent significant progress in treatment capabilities.
“These medications unleash a patient’s already present anti-cancer immune response that has been suppressed by the cancer,” Fehrenbacher told ADVANCE. “Two of these drugs are currently approved, and a number of other drugs working by the same mechanism of checkpoint inhibition are in late stage clinical trials.”
Pembrolizumab was approved by the FDA in October 2015 for the treatment of metastatic non-small cell lung cancer in patients whose tumors express PD-L1 (a trans-membrane protein that has been speculated to play a major role in suppressing the immune system) and who have failed treatment with other chemotherapeutic agents. Nivolumab was approved by the FDA for treatment of patients with squamous non-small cell lung cancer. Among the drugs in clinical trials is atezolizumab, under investigation by Genentech and Roche for treatment of melanoma, breast cancer, non-small-cell lung carcinoma, bladder cancer and renal cell carcinoma.
These immune checkpoint inhibitors are nothing short of a game changer in the lung cancer space, Fehrenbacher enthused. “Hopefully they will become even more effective as we learn when and how best to use them. They appear to be more effective and less toxic than standard chemotherapies in a number of settings, particularly in relapsed lung cancer patients.”
Fehrenbacher pointed to a second category of drugs-oral “targeted drugs” that block mutated growth stimulating proteins produced by cancer cells that have a very specific and defined DNA mutation-as another wave of hope in the fight against ling cancer.
“Very specific mutations occur in genes that normally make EGFR, ALK, ROS and other proteins,” he explained.
“These mutation-derived proteins drive cancer growth but can be stopped by specific treatment molecules that stop the mutated proteins from functioning. Examples of these protein-halting medications are erlotinib and afatinib for EGFR mutated cancers and crizotinib and alectinib for ALK driven cancers,” Fehrenbacher said. “These targeted drugs, when used in patients with specific mutations, are also more effective and have less side effects than chemotherapy. And some drugs, alectinib for example, also can get into the brain and treat lung cancer brain metastases that chemotherapy cannot reach.”
Fehrenbacher reminded that lung cancer is the cause of more deaths than any other cancer by far and traditionally has been extremely hard to treat, “with the majority of patients eventually dying of the disease. The new drugs are an advance in the metastatic setting and it is hoped they will be successful in the adjuvant post-surgery setting in the future. Those trials in the adjuvant setting are yet to be done.”
The good news of the new therapies are emerging with a lot of fanfare, publicity and even direct-to-patient advertising. Their use in lung cancer and melanoma is rising monthly, as the information is more available and widespread, said Fehrenbacher. “There are rapid advancements being made the use these checkpoint inhibitors, discovery of new checkpoint inhibitors, determining which patients will respond, and managing toxicity. The number of cancers responding to these immune therapies is increasing every few months as trial results are reported. History has told us that it takes a number of years to maximize the benefits of a new class of treatments, so hopes are high. And patients are understandably asking about them with high expectations.”
But Fehrenbacher would remind others in healthcare that these newer drugs require the input of clinical trials to become reality. “Participation in clinical trials of these agents is our pathway to more successes in the future.”