When Ravi Salgia, M.D., Ph.D ., looks out at the lung cancer landscape, he sees hope and promise where very little existed not that many years ago. He’s clear about his goal.
“The goal is to cure,” said Dr. Salgia, the Arthur & Rosalie Kaplan Chair in Medical Oncology & Therapeutics Research at City of Hope®. “In the most efficacious way, with the least toxicity. Even metastatic lung cancer has to be cured.”
Typical chemotherapy kills cancer cells, but also wreaks havoc on normal cells. When chemotherapy was the only drug option, doctors had to balance the potential good with the possible harm.
New classes of drugs have changed everything for the better, to the point where even Stage 4 lung cancer can be successfully treated. Targeted therapy drugs attach to genetic anomalies in lung tumors, leaving healthy cells alone. Immunotherapy trains the body’s immune system to seek out and destroy cancer cells, and only cancer cells.
Even chemotherapy has changed, with new ways of delivering its lethal punch without potentially harming nearby healthy tissue.
Here are some of the latest advances in lung cancer treatment.
The Latest Lung Cancer Immunotherapies
Originally approved for breast cancer, trastuzumab deruxtecan (brand name Enhertu) is a two-drug combination called an antibody-drug conjugate (ADC) that fights advanced non-small cell lung cancer in two ways. A monoclonal antibody — trastuzumab — seeks out and attaches itself to HER2 mutations found in some lung tumors (as well as in HER2-positive breast cancer). Once there, it delivers a powerful dose of chemotherapy — deruxtecan — which attacks and kills the cancer cells. For patients with HER2 mutations, this is a major new option. “It’s very exciting,” said Dr. Salgia.
Approved in May 2024, tarlatamab (brand name Imdelltra) is an immunotherapy drug for patients with the aggressive and relatively rare (14% of all cases) small cell lung cancer, which until now has had limited treatment options. It is a bispecific T cell engager that attaches to tumor cells as well as T cells, enabling those immune cells to recognize and shrink the tumor.
Lazertinib (brand name Leclaza) is a tyrosine kinase inhibitor that works on non-small cell lung cancer patients with the EGFR mutation. For those expressing the ALK mutation, there is excitement about lorlatinib (brand name Lobrena), especially for its ability to stop lung cancer from spreading to the brain. “We’re seeing huge survival rates,” said Dr. Salgia. Another tyrosine kinase inhibitor, selpercatinib (brand name Retevmo) has been shown to be effective in the small percentage of lung cancer patients with alterations in the RET gene.
Dr. Salgia wants more. “We have to go beyond precision medicine, using it as a tool to achieve personalized medicine, which takes into account a patient’s age, race, type of tumor and more.” He wants that personalization available to everybody. His vision includes “clinical trials taking place at every City of Hope site, patients being monitored in their own homes, and perhaps even doctors making home visits, making it as easy as possible to get treatment.”
Breakthroughs in Radiation Therapy
Radiation therapy has come a long way since the first patients were treated back in 1901, with advances arriving virtually every decade. The march of progress continues today, especially in the last 10 to 20 years.
Early radiation machines targeted a wide area beyond the cancer, endangering neighboring healthy tissue. Those machines also couldn’t handle more than one lesion at a time. Nor could they adapt to a patient accidentally moving, or even breathing, thereby shifting the target — especially the case with lung cancer. Doctors had to set larger margins around the tumor to make sure all the cancer cells were hit, and they had to keep radiation doses low.
These problems have largely been solved.
“The technology has so improved,” said radiation oncologist Arya Amini, M.D., chief of thoracic radiotherapy and associate professor in the Department of Radiation Oncology at City of Hope, “that we’re able to target tumors with smaller margins and avoid collateral damage to other organs. We can also target multiple lesions at the same time.”
Dr. Amini has a stable of state-of-the-art tools at his disposal. Four-dimensional computed tomography is a typical example of image-guided treatment taken to the next level. 4DCT improves on conventional CT scans by taking a series of images over a 30-second period to reveal the patient’s breathing motion and how it moves the tumor. The result is an accurate roadmap for aiming the radiation beams.
Another advance uses laser technology to track a patient’s movement during the radiation procedure itself and correct for it. This surface-guided radiation therapy (SGRT) makes it possible to work with smaller margins.
An even newer machine tackles the same challenges from the inside out. City of Hope is one of the first institutions to use SCINTIX technology. SCINTIX is a form of biologically guided radiotherapy. The patient receives a radiotracer by injection. The radiotracer “lights up” cancer cells on a PET scan, tracking them in real time, even when they move. This system enables technicians to target and treat multiple areas at the same time.
The more precise the targeting, the more leeway for doctors to adjust the radiation dosage. When there’s relatively little risk of harming nearby organs, it becomes possible to increase the beams’ intensity, so treatments are more effective and take less time. Stereotactic body radiotherapy, or SBRT, (“My favorite,” says Dr. Amini) takes full advantage of this, deploying hundreds of precisely targeted radiation beams in just five treatments or fewer.
Taken together, Dr. Amini says these new radiotherapy tools are capable of transforming Stage 4 lung cancer from a terminal illness into a chronic disease. “I have [late-stage] patients from when I started at City of Hope — over seven years ago — and they’re still here,” he says. “I am very excited about the potential of today’s radiation treatments to keep our patients alive for years and years and years.”