Will Immunotherapy Work For Me? Predicting Lung Cancer Treatment Outcomes

“Immunotherapy or checkpoint inhibitors have really revolutionized this space,” Dr. Isabelle Preeshagul, a thoracic medical oncologist at Memorial Sloan Kettering Cancer Center, tells SurvivorNet, adding that measuring the expression of these proteins in patients helps doctors determine the best treatment approach — but it’s not the only factor.

PD-L1’s Role In Lung Cancer Treatment

When PD-L1 inhibitors were originally approved for use, it was based on how high a patient’s PD-L1 expression on their tumor was, Dr. Preeshagul explains.

“Based on the keynote study, KEYNOTE-024 pembrolizumab — or Keytruda — was approved if your PD-L1 was greater than 50%,” she says.

Before starting a checkpoint inhibitor or offering this class of medicine to patients, medical oncologists order a laboratory test that measures how much PD-L1 protein is present on the surface of the tumor (the “tumor proportion score,” or TPS). Tumors with TPS of greater than or equal to 50% are considered “high expressers.” Those with 1-49% are “intermediate,” and those with  less than 1% are “negative.”

The higher the PD-L1 level, the more likely pembrolizumab alone is to shrink or stabilize the cancer.

Conversely, patients with lower PD-L1 expression can still benefit from pembrolizumab, but usually in combination with chemotherapy. As. Dr. Preeshagul mentions, this correlation between PD-L1 and therapeutic response was first shown in the phase-III KEYNOTE-024 trial — but PD-L1 expression is not the only relevant factor.

“I have patients with a PD-L1 of 100% and they don’t respond to immunotherapy. And then I have patients with a PD-L1 of 1% or less than 1%, and they get chemotherapy and immunotherapy and sometimes they can’t tolerate the chemo and we just continue them on immunotherapy alone and they’re doing great,” Dr. Preeshagul explains. “I think that what this is telling us is that it’s much more than just PD-L1.”

How Much Can PD-L1 Tell Us?

In clinical trials, the likelihood of a good response to pembrolizumab rises as PD-L1 TPS goes up.

In the early-phase KEYNOTE-001 study, tumors expressing PD-L1 on ≥50% of cells shrank in about 45% of patients vs. roughly 10-20% when expression was low or absent.

KEYNOTE-024 later confirmed that high-expressers gained the greatest survival benefit from pembrolizumab alone. That said, PD-L1 is an imperfect predictor — some people with very high scores do not respond, while a meaningful minority with low (<1 %) or intermediate (1-49%) PD-L1 expression still benefit, especially when the drug is paired with chemotherapy.

“It’s really all about the tumor microenvironment,” Dr. Preeshagul explains. “Is it the tumor mutation burden or is it just the fact that perhaps patients that have a heavier smoking history are thought to have more agitated tumors and a higher tumor mutation burden because of their tobacco exposure … I don’t think right now we know the answer to that.”

Differences in testing methods, sample quality, and the fact that tumors can change their PD-L1 status over time all limit how “assertive” the marker can be. Think of it as a strong hint, not a guarantee, when choosing the best treatment plan.

Who Can Get Pembrolizumab [Keytruda]?

Because of studies like KEYNOTE-024 (just pembrolizumab) and KEYNOTE-189/-407 (pembrolizumab plus chemotherapy), the drug now has U.S. FDA approvals in multiple lung-cancer settings, including:

• As a first-line (first treatment) for metastatic NSCLC in patients with PD-L1 expression equal to or greater than 50%
• As a first-line treatment combined with platinum-doublet chemotherapy for patients with metastatic NSCLC and any PD-L1 level
• As a treatment given alongside chemotherapy before surgery for patients with operable stage II and III NSCLC and given alone after surgery

What Is Treatment Like?

Pembrolizumab is administered through intravenous infusion, every three or six weeks, and usually given in an outpatient infusion center. Based on your overall health, disease stage, and side effects, your doctor will decide the best duration of the treatment. Commonly, many clinicians treat for up to two years if the cancer keeps responding and side effects remain manageable.

Patients are monitored with CT scans every 6 to 12 weeks at first. Bloodwork checks are done before each infusion to check for low blood cell count and other abnormalities.

Possible side effects include:

• Fatigue
• Itching or rash
• Decreased appetite
• Joint pains

Less common but important “immune-related” effects include pneumonitis (lung inflammation), colitis (diarrhea), hepatitis, thyroid or adrenal gland irritation, and skin reactions.

These can occur weeks or even months after the last dose and often improve with prompt steroid treatment.

Living With Cancer

Many people tolerate immunotherapy better than chemotherapy. There are often fewer difficult side effects like hair loss, nausea, and neuropathy.

Some patients experience a rapid improvement in breathing or energy as tumors shrink, while others may not see changes on scans for several months.

Because immunotherapy accelerates the whole immune system, doctors and patients should be cautious for new or unusual symptoms  such as persistent cough, severe diarrhea, yellowing of the eyes, unexplained headaches, and skin blistering.

The presence or persistence of any symptoms should be promptly reported to healthcare providers, as early management often prevents serious complications.

Questions To Ask Your Doctor

• Has my tumor been tested for PD-L1, EGFR, ALK, and other markers? What do the results mean for my treatment options?
• What short- and long-term side-effects should I watch for?
• How often will I need scans and clinic visits?
• If I have an autoimmune disease or take immunosuppressive medicines, can I still receive checkpoint inhibitors safely?

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