Could Timing Give Your Cancer Treatment A Boost? New Study On The Best Time To Receive Immunotherapy & Chemo For Non-Small Cell Lung Cancer

However, other experts, such as Dr. Paolo Tarantino, a breast medical oncologist at Dana‑Farber, were more cautious. “We need a coordinated effort between academia and pharma to re‑examine past randomized trials and understand this more clearly — for the safety of our patients,” Dr. Tarantino says.

WATCH: Guide to Late-Stage Lung Cancer Immunotherapy Options

The Daily Rhythm Of Cells

Observational research has long suggested that treatment earlier in the day seemed to be associated with better results, but this is the first time a randomized trial has confirmed the association.

“It has always been hypothesized that our immune system may be affected by our circadian rhythm. This means that immune cells may function differently in the morning than in the late afternoon or evening,” Dr. Joshua Sabari, an oncologist at NYU Langone Health, explains.

The circadian rhythm is a natural 24-hour cycle that the body goes through every day. It regulates hormonal, behavioral, and biological processes throughout the day.

Disrupting the circadian rhythm — due to sleep disorders, chronic jet lag, or night shift work, for example — increases the risk of the most common types of cancer.

WATCH: Nobel Prize Winner: What’s Next For Using Immunotherapy to Save Lives?

What The LungTIME-C01 Trial Found

The phase 3 LungTIME-C01 (NCT05549037) clinical trial enrolled 210 people in China with untreated non-small cell lung cancer (NSCLC) who were randomly assigned to receive treatment before 3 PM or after 3 PM.

The participants had advanced (stage IIIC or IV) lung cancer that did not have any driver mutations. All patients were treated with four cycles of immunochemotherapy, a combination of the immunotherapy drug pembrolizumab (brand name: Keytruda) and chemotherapy, which included an anti-PD-1 agent (generic name: sitilimab).

After a median follow-up of just over two years, the median progression-free survival (PFS) was 11.3 months in the early time-of-day group. In the late time-of-day group, the median PFS was 5.7 months. PFS is the amount of time after treatment begins without the disease getting worse.

In the early group, the median overall survival (OS) was 28 months, compared to 16.8 months in the late group.

“This simple, non-pharmacologic factor — the time of day treatment is delivered — was associated with meaningful improvements in progression-free and overall survival in a randomized trial … suggesting enhanced T-cell activity earlier in the day,” Dr. Velcheti. explains. If validated, this work could introduce treatment timing as a new dimension of personalization in lung cancer care, encouraging earlier-day administration of immunotherapy when feasible to align with circadian immune biology.”

WATCH: Immunotherapy for Advanced Lung Cancer

Differences In “Killer” Immune Cells

When researchers looked at the behavior of certain immune cells, they found that the people treated earlier in the day had more circulating Cytotoxic T cells (also called CD8+ T cells) in the morning. They also had more activated CD8+ T cells compared to exhausted CD8+ T cells.

These immune cells are known as “killer” cells. They are activated by the immune system to destroy dangerous cells, such as viruses, bacteria, and cancer cells. Having more circulating CD8+ T cells and a higher ratio of activated to exhausted CD8+ T cells is a sign that CD8+ T cells are more effectively controlling the cancer.

“The benefit may be due to circulating CD8+ T cells, which may be enhanced in those patients receiving chemoimmunotherapy earlier in the day over those receiving therapy later in the day,” said Dr. Sabari.

Looking Ahead: Will This Study Lead To Changes In Clinic Schedules?

Right now, it is unclear how this will impact clinic schedules, but some oncologists are calling for urgent research. On X, Dr. Tarantino said, “This is possibly the most controversial finding in immuno-oncology. The effect size is hard to believe. Though [randomized clinical trials] are NOT hard to believe.”

“We need to better understand the specific mechanisms that led to this observation,” says Dr. Suresh Ramalingam at the Emory Winship Cancer Institute. “From a practical standpoint, this should be easy to implement in the clinic. It should be noted that this is mainly related to the first cycle of therapy, since for subsequent cycles, the time of day may matter less.”

This is because in later treatment cycles, the immunotherapy has built up in the body.

“If validated, this work could introduce treatment timing as a new dimension of personalization in lung cancer care,” says Dr. Velcheti. “Translating this into practice will require thoughtful consideration of clinic workflows, infusion capacity, and patient logistics — but the simplicity and low cost of the intervention make it a particularly intriguing and potentially impactful finding.”

If you’re receiving immunochemotherapy or considering it, timing isn’t part of the standard of care yet. This early study is promising, but researchers say more evidence is needed before treatment schedules change.

As with many early studies, it’s natural for parts of the cancer community to feel excited about the potential. But SurvivorNet leans toward measured optimism — more research is needed before findings like these can influence standard care or move toward federal approval. We’ll continue tracking this trial closely and will share updates as new information emerges.

Immunotherapy Continues To Be A Game Changer In Cancer Care

SurvivorNet spoke with the pioneer in immunotherapy research, Dr. James (Jim) Allison at MD Anderson Cancer Center, who was awarded a Nobel Prize for the development of the science called checkpoint inhibitors.

RELATED: “Breakthrough,” The Film About Nobel Prize Winner Jim Allison And The Invention Saving Millions of Lives; Learn How Immunotherapy Can Help Late-Stage Lung Cancer

“Immunotherapy is rather unique in that for the first time, we’re getting truly curative therapies in many kinds of disease — not just in melanoma but in lung cancer, kidney cancer, bladder cancer, Hodgkin’s lymphoma, Merkel cell cancer, head and neck cancer,” Dr. Allison said.

“I think that the most powerful combinations coming up are based on combining immune blockers or enhancers, but also drugs that can directly kill tumor cells to really have a double whammy,” Dr. Allison added.

Checkpoint inhibitors, like pembrolizumab, help the immune system do its job by removing the “invisibility cloak” that cancer cells use to hide. Normally, a protein called PD-1 acts like a brake on T cells, keeping them from attacking healthy cells. But cancer takes advantage of that brake to avoid being targeted. Pembrolizumab blocks PD-1, releasing the brake and letting T cells go after cancer cells more aggressively — just like they’re meant to.

Immunotherapy Side Effects

Patients taking the immunotherapy drug Keytruda (pembrolizumab) should be aware of some of its known side effects. These vary based on whether you’re taking Keytruda alone or in combination with other drugs.

The most common side effects of Keytruda alone include:

• Fatigue
• Muscle/bone/joint pain
• Rash
• Diarrhea
• Cough
• Fever
• Changes in appetite
• Itching
• Shortness of breath
• Abdominal pain and/or nausea
• Low thyroid hormone

If you’re taking Keytruda with other medications, you may experience additional side effects. For example, if you’re taking Keytruda with chemotherapy, you may experience weakness or nerve pain. This is not a complete list of side effects.

Questions To Ask Your Doctor

• How will immunochemotherapy work for my specific type and stage of cancer, and what results are realistic for me?
• What factors about timing and logistics should we consider when making my treatment plan?
• What side effects should I expect from immunochemotherapy, and how can we manage them?
• How often will I need treatment, and how might it affect my daily routine, work, or energy levels?

Learn more about SurvivorNet's rigorous medical review process.