Response and safety profile of neoadjuvant nivolumab for resectable lung cancer

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Published: 25 Apr 2018
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Dr Drew Pardoll - Johns Hopkins Medicine, Baltimore, USA

Dr Pardoll speaks with ecancer at AACR 2018 about outcomes from a trial of 20 patients who received anti-PD1 nivolumab before surgical resection.

Pathological responses were observed in 45% of patients and, at a median follow-up of 12 months, 16 patients remain recurrence free.

Dr Pardoll discusses the staging and followup of this trial group, and its prospects for further investigation.

Watch his presentation of these results at the conference here.

What I reported was the results of the first ever neoadjuvant clinical trial of a PD1 blocker for patients with operable lung cancer. This is giving anti-PD1, this very exciting immunotherapy, at the earliest stage in cancer that it’s ever been given, namely prior to surgery in patients that have localised lung cancer. We know that the majority of those patients, even though we can only see the tumour in the lung, have a few cells that have broken off and have lodged elsewhere in the body. We can’t see them but they are the source of relapses that occur after resection from lung cancer and they are, therefore, the sources of the reasons that operable lung cancer patients ultimately still go on to die of their recurrent lung cancer.

The idea here was to use the tumour in place before surgery as almost an auto-vaccine to stimulate anti-tumour T-cells, first within the tumour and then with the idea that they would leave the tumour and then circulate through the body seeking out to destroy and intercept those few cells that have lodged elsewhere that will eventually cause the relapse. We were able to show that in close to half of the patients the vast majority of their primary tumour was overrun by lymphocytes upon the PD1 therapy. We were also able to show in a selected set of patients that T-cells specific for their cancer did, in fact, migrate out into the blood, into their circulation. It’s a small study but to date with a follow-up between one and two years after surgery only one patient has died of recurrent cancer. This is very encouraging but we need to see the results of larger studies. Fortunately this very encouraging result has launched a huge number of much larger neoadjuvant clinical trials, at last count as many as 75, with hundreds of patients being treated. So we’ll know whether this stands up but we’re certainly very hopeful that these early results suggest that moving this immunotherapy earlier is going to really make a difference and be potentially practice changing for lung cancer patients. I should also mention that there are seven other cancer types that now have neoadjuvant PD1 blocking therapies that are being tested as well.

What kind of response did you see?

45% of patients had a major pathologic response defined as less than 10% of the living cells in the tumour resection were actually cancer cells. Actually three of the twenty patients had a complete pathologic response which means that in the whole tumour that was resected there was not a single living cancer cell that the pathologist was able to identify.

How did you measure the response after resection?

We were able to measure tumour specific T-cells. In fact with a new assay we could identify T-cells specific for mutations in the tumour. So these are true tumour specific T-cells that increased in the blood very rapidly after initiation of the immunotherapy and persisted after surgery. In terms of being able to follow evidence of the actual tumour through circulating free tumour DNA , these are studies that are currently ongoing.

Are you excited about the potential of neoadjuvant combination therapies?

Absolutely excited about that; there’s no reason to believe that the combination therapies that have moved the ball forward in metastatic advanced lung cancer and other cancers won’t be able to potentially similarly increase the benefit to neoadjuvant therapy. Actually a large proportion of the clinical trials that have been launched since our trial in fact contain groups of patients that are using combinations that add something else to the PD1 blocker.

What else is to come in the preclinical setting over the next year?

Lots and lots of things. Most will include a PD1 pathway blocker but we’re testing vaccines, cancer vaccines, in conjunction with an anti-PD1 in the neoadjuvant setting. Combinations of checkpoint blockers in the neoadjuvant setting and also the use of radiation therapy in the pre-surgical, prior to surgery, again in combination with immunotherapy to boost the anti-tumour immune response