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

April 16, 2018, American Association for Cancer Research

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 to data from a clinical trial presented at the AACR Annual Meeting 2018, April 14-18.

A major pathologic is defined as 10 percent or fewer viable cancer cells detectable in the resected tumor following neoadjuvant treatment.

This study is being simultaneously published in the New England Journal of Medicine.

"The rationale for neoadjuvant anti-PD1 treatment of resectable NSCLC was essentially to use the primary tumor as a "vaccine" to induce T cells against the tumor antigens that would then circulate through the body systemically and seek out any distant sites of micrometastases," said senior author of the study Drew Pardoll, MD, Ph.D., director of Bloomberg~Kimmel Institute for Cancer Immunotherapy and director of Cancer Immunology at Johns Hopkins School of Medicine. "Micrometastases are the primary source of relapse after surgery."

Conventional neoadjuvant therapy, chiefly comprising chemotherapy or chemoradiotherapy, is given to lung cancer to shrink a large, non-metastasized tumor located near an important organ or a blood vessel. The tumor is temporarily shrunk prior to surgery to improve surgical outcomes, Pardoll explained.

"The most stunning finding was that nine of the 20 patients who had surgery after neoadjuvant anti-PD1 had a major pathologic response," Pardoll noted. "Two patients had no evidence of viable cells in the resected specimen. This is particularly striking given that surgery was done, in most cases, just four weeks after the first dose of anti-PD1 treatment."

He added, "Our result of a 45 percent major pathologic response rate is very encouraging, considering prior studies showing that a major pathologic response after neoadjuvant chemotherapy in is associated with long-term survival."

Pardoll and colleagues enrolled 21 patients with stage 1-3A NSCLC in this trial between August 2015 and October 2016; 62 percent had adenocarcinoma. All patients received at least one dose of nivolumab. The median time from second dose of nivolumab to surgery was 18 days, and 20 of 21 eligible patients underwent complete tumor resection. "The anti-PD1 treatment was tolerated well and there were no surgical delays related to neoadjuvant treatment," Pardoll noted.

Major pathologic responses were observed in the patients' tumors irrespective of PD-L1 expression by tumor cells. Tumor mutation burden closely predicted the degree of pathologic response. After a median follow-up of 12 months, 16 of 20 patients who underwent surgical resection were alive and recurrence-free. Recurrence-free survival at 18 months was 73 percent, and the median recurrence-free survival had not been reached at the time of data analysis.

To test their hypothesis that checkpoint blockade induces the expansion of tumor-specific T cells in the circulation, the researchers analyzed T-cell responses in the blood on the day of nivolumab treatment and 44 days after surgery. "There was a big burst of tumor-specific T cells in the blood within, in most cases, four weeks after initiation of anti-PD1 treatment suggesting that neoadjuvant may have enhanced antitumor immunity systemically," Pardoll said.

"While it is still too early to tell whether our findings will translate into lower relapse rate and improved survival, pending confirmation in a larger study, we are very optimistic that this approach will eventually be practice-changing and may augment or even replace chemotherapy prior to ," Pardoll said.

"We have to be careful not to compare these outcomes with historical outcomes given the small size of this single-arm study; however these initial results are highly encouraging and, allied to the translational science, will spur interest in further neoadjuvant clinical trials across types," concluded study leader and co-principal investigator of the trial, Patrick Forde, MBBCh, assistant professor of oncology at Bloomberg~Kimmel Institute for Cancer Immunotherapy.

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

Related Stories

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.

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 ...

Research is changing the game for melanoma treatment

February 1, 2018
Wilmot Cancer Institute patients with advanced melanoma (stage III) now have more options for treatment, thanks to research co-authored by a University of Rochester Medical Center surgical oncologist and published in The ...

Adjuvant chemotherapy improves overall survival in patients with stage IB non-small cell lung cancer

June 13, 2016
The use of adjuvant chemotherapy in early-stage non-small cell lung cancer (NSCLC) patients improves overall survival (OS) and 5-year OS in patients with tumor sizes ranging from 3 - 7 cm.

Radiation prior to surgery reduces risk of secondary tumors in early-stage breast cancer

July 17, 2017
Moffitt Cancer Center researchers launched a first of its kind study comparing the long-term benefits of radiation therapy in women with breast cancer either before surgery (neoadjuvant) or after surgery (adjuvant). Their ...

Researchers to present event-free and overall survival results from NeoALTTO trial

December 11, 2013
Results from the initial analysis of event-free and overall survival for patients enrolled in the randomized, phase III Neoadjuvant Lapatinib and/or Trastuzumab Treatment Optimization (NeoALTTO) trial are to be presented ...

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.