Drug reduces size of some lung cancer tumors, relapse rate after surgery

April 16, 2018, Johns Hopkins University School of Medicine
The research teams discovered new infiltration of immune cells into the lung cancer after nivolumab, an anti-PD-1 drug, was administered. Credit: Johns Hopkins Kimmel Cancer Center

A drug given to early stage lung cancer patients before they undergo surgery showed major tumor responses in the removed tumor and an increase in anti-tumor T-cells that remained after the tumor was removed, which resulted in fewer relapse cases in the patients.

The research teams at the Johns Hopkins Bloomberg~Kimmel Institute for Cancer Immunotherapy, the Johns Hopkins Sidney Kimmel Cancer Center and the Memorial Sloan-Kettering Cancer Center wanted to find out if providing nivolumab, an anti-PD-1 drug, would stimulate anti- immunity in patients with (NSCLC) who were going to have their tumors surgically removed.

The study showed after 21 patients received two doses of nivolumab before surgery, there was a major pathologic response in 45 percent of the removed tumors and no delays in any of the planned surgeries. In addition, neoantigen-specific T-cell clones were stimulated by the drug and present in the blood and tumor but disappeared from the body after the tumor was removed.

The study was published in the New England Journal of Medicine on April 16, 2018.

"We wanted to look at the patients' tumor and immune system prior to treatment and examine it again after treatment for changes," said Patrick Forde, M.B.B.Ch., first author and co-principle investigator of the trial and a lung cancer oncologist in the Bloomberg~Kimmel Institute of Cancer Immunotherapy. "We found tumor regression in almost half of these early stage . We weren't expecting to see major pathology with only two doses (of nivolumab)."

Forde said the number of gene mutations in the tumor correlated closely with response to treatment and was a potential predictive marker for future studies. The research teams discovered new infiltration of immune cells into the lung cancer after the drug was administered.

"Given that phase 3 clinical trials are underway, using this neoadjuvant anti-PD-1 drug will likely be practice changing," said Drew Pardoll, M.D., Ph.D., senior author, director of the Bloomberg-Kimmel Institute for Cancer Immunotherapy and co-director of the Cancer Immunology Program at the Kimmel Cancer Center.

"There was a major pathological response in almost half the patients, the tumor was almost totally overrun by lymphocytes at the time of resection, and we were able to demonstrate using a new assay we developed that tumor-specific T-cells spilled out into the blood after treatment."

Twenty-one patients enrolled in the study were 18 years of age and older and had stage I, II or IIIA NSCLC that was deemed resectable. Twenty of the 21 received 3 mg/kg of nivolumab intravenously every two weeks for two doses prior to surgery. One patient underwent an uncomplicated surgery after only one dose.

Twenty patients underwent complete tumor resection after receiving the drug. Upon follow-up after surgery, 16 of the 20 patients were alive and recurrence-free. One patient without recurrence died from a traumatic head injury unrelated to the study.

Three patients experienced tumor relapse. Two of the patients underwent further treatment and have not had further recurrence. One patient died of relapsed metastatic cancer about 16 months after surgical resection.

Pardoll said historically, approximately 50 percent of NSCLC patients who undergo surgery will relapse. Chemotherapy can add about 5 percent to survival but introduces toxicity to surrounding tissue. The results from the study showed neoadjuvant anti-PD-1 treatment could enhance the priming of anti-tumor T-cells, potentially eliminating micro-metastatic cancer that can cause post-surgical relapse.

"That T-cells, activated by immunotherapy prior to surgery, can intercept rogue tumor cells throughout the body after the patient's operation and prevent the cancer from recurring may be a game-changer. This notion of 'cancer interception' has the potential to stop cancer in its tracks, helping turn patients into long-term survivors, and it is a significant focus for (Stand Up To Cancer). We look forward to learning the results of the follow-up clinical studies that are underway to see how this breakthrough benefits a larger number of patients," said Stand Up To Cancer President and CEO Sung Poblete, Ph.D., RN.

Larger studies are needed to examine the effects of combination immunotherapies, longer courses of a neoadjuvant drug and to define the role of the anti-PD-1 in reducing recurrences and curing early stage cancers.

"The potential to transform treatment of resulting from this groundbreaking work by Forde, Pardoll, and other members of the SU2C-CRI Immunology Dream Team demonstrates the power of cross-disciplinary collaboration to advance lifesaving translational research, where the laboratory and clinic meet, and underscores the importance of continued efforts to explore fully immunotherapy's promise at various stages of treatment along the entire patient journey," said Jill O'Donnell-Tormey, Ph.D., CEO and director of scientific affairs at the Cancer Research Institute.

Explore further: Expansion of circulating tumor-specific T cells after treatment suggested systemic antitumor immunity

Related Stories

Expansion of circulating tumor-specific T cells after treatment suggested systemic antitumor immunity

April 16, 2018
The anti-PD1 immunotherapy nivolumab (Opdivo) given prior to surgical resection of stage 1-3 non-small cell lung cancer (NSCLC) was safe and resulted in major pathological responses in 45 percent of the patients, according ...

Researchers find promising treatment strategy for stage 1-3 NSCL cancer patients

April 16, 2018
A new, innovative approach to lung cancer treatment in which immunotherapy is administered prior to surgery is yielding encouraging outcomes in 45% of patients treated in this small, compelling study from researchers on the ...

Using pre-surgical anti-PD 1 therapy in melanoma patients can identify those most likely to benefit

April 16, 2018
Checkpoint inhibitors that block the protein PD-1 are used in melanoma patients after they've had surgery to remove their cancer, but not all patients benefit from the immunotherapy. Now a new study from the Abramson Cancer ...

Neoadjuvant immunotherapy prior to surgery is safe and feasible in early lung cancer

October 7, 2016
Neoadjuvant immunotherapy with the PD-1 inhibitor nivolumab is safe and feasible prior to surgery for early lung cancer, researchers reported at the ESMO 2016 Congress in Copenhagen.

Researchers discover new approach to stimulate an immune response against tumor cells

January 30, 2018
New drugs that activate the immune system to target cancer cells have improved the lives of many patients with cancer. However, immunotherapies are not effective in all patients, and the success of these therapies depends ...

Five-year survival rate for nivolumab-treated advanced lung cancer patients much higher than historical rate

April 3, 2017
Treatment with the immune checkpoint inhibitor nivolumab (Opdivo) yielded durable responses in some patients with advanced non-small cell lung cancer (NSCLC), with a five-year survival rate of 16 percent, according to data ...

Recommended for you

Single-cell study in a childhood brain tumor affirms the importance of context

April 20, 2018
In defining the cellular context of diffuse midline gliomas, researchers find the cells fueling their growth and suggest a potential approach to treating them: forcing their cells to be more mature.

Aggressive breast cancer already has resistant tumour cells prior to chemotherapy

April 20, 2018
Difficult to treat and aggressive "triple-negative" breast cancer is chemoresistant even before chemotherapy begins, a new study by researchers from Karolinska Institutet and the University of Texas MD Anderson Cancer Center ...

Mechanism that drives development of liver cancer brought on by non-alcoholic fatty liver disease discovered

April 19, 2018
A team of researchers from several institutions in China has found a mechanism that appears to drive the development of a type of liver cancer not caused by alcohol consumption. In their paper published in the journal Science ...

Discovery adds to evidence that some children are predisposed to develop leukemia

April 19, 2018
St. Jude Children's Research Hospital researchers have made a discovery that expands the list of genes to include when screening individuals for possible increased susceptibility to childhood leukemia. The finding is reported ...

Scientists identify 170 potential lung cancer drug targets using unique cellular library

April 19, 2018
After testing more than 200,000 chemical compounds, UT Southwestern's Simmons Cancer Center researchers have identified 170 chemicals that are potential candidates for development into drug therapies for lung cancer.

Chip-based blood test for multiple myeloma could make bone biopsies a relic of the past

April 19, 2018
The diagnosis and treatment of multiple myeloma, a cancer affecting plasma cells, traditionally forces patients to suffer through a painful bone biopsy. During that procedure, doctors insert a bone-biopsy needle through an ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.