Immunotherapy for lung cancer (Part 1): Neoadjuvant and adjuvant immunotherapy

Immunotherapy is a cancer treatment that uses medicines to stimulate your own immune system to detect and destroy cancer cells, helping to improve outcomes for people fighting lung cancer.

Dr Crispin Hiley is a highly renowned consultant clinical oncologist and associate professor who specialises in all the different types of lung cancer, as well as cancer immunotherapy and chemotherapy. In the first of a two-part series of articles on immunotherapy for lung cancer, Dr Hiley offers an expert insight into neoadjuvant and adjuvant immunotherapy for lung cancer.

What is neoadjuvant immunotherapy and its aim?

Neoadjuvant immunotherapy is a treatment given before surgery.

Many patients with early or locally advanced lung cancer are treated with surgery. For a long time, early or locally advanced lung cancer that had spread to the lymph nodes, as well as large cancers (for example, bigger than four centimetres), would be treated with surgery followed by chemotherapy. Adjuvant chemotherapy, as this is known, is given once all the cancer has been removed surgically to reduce the risk of any cancer coming back.

More recently, some clinical trials have studied the use of other agents - including immunotherapy - either before surgery (for neoadjuvant therapy) or after surgery (for adjuvant therapy).

With neoadjuvant immunotherapy, the CheckMate 816 trial study showed that there was significant benefit in giving some patients chemotherapy and immunotherapy before surgery. During the clinical trial, the patients received three cycles (or three courses) of chemotherapy and nivolumab, and then underwent surgery. Following surgery, the Checkmate 816 study showed that there was significant benefit in the reduction of the risk of cancer recurrence. Treatment worked very well for some patients, and when the tumour was examined under a microscope after it was removed during surgery, it was very difficult to find any active cancer left following neoadjuvant treatment and surgery.

Patients with a very good response to neoadjuvant treatment have had very good long-term outcomes from all of these trials of neoadjuvant chemotherapy and immunotherapy, so far. The use of neoadjuvant immunotherapy in combination with chemotherapy will become more prevalent over the coming years among patients where surgery is planned for their lung cancer. However, it is important to know that immunotherapy for lung cancer is mainly used for patients with no actionable mutation, such as an EGFR mutation or an ALK mutation.

Can you give some examples of neoadjuvant therapy and what is involved in their processes?

Neoadjuvant therapy for lung cancer can involve many different treatments.

Patients with no actionable mutation (no EGFR or ALK mutations) are now being treated with chemotherapy and immunotherapy, with three cycles of this treatment (platinum-based chemotherapy and nivolumab) prior to surgery. During the process, these patients come to hospital to have chemotherapy and immunotherapy at the start of a three-week course of treatment, which is given intravenously. The patients then return to the hospital three weeks later to receive another three-week course of treatment. Before each new cycle of treatment, the patients need to be seen by their oncologist to see if the treatment is being well-tolerated. Once three three-week courses of treatment have been finished, the patients undergo surgery. This is becoming a very common type of neoadjuvant treatment used for patients with lung cancer.

Despite this, other forms of neoadjuvant treatment are also used for patients with lung cancer. Some patients, for example, may be offered neoadjuvant chemoradiotherapy (chemotherapy and radiotherapy both) prior to surgery. This treatment type is mostly offered to patients who have cancers in particular positions within the lung that would be difficult to take out and thus, there is a risk that some cancer may be left behind after surgery.

In the future, patients with actionable mutations (for example, an EGFR mutation) may start to be offered neoadjuvant treatments, such as neoadjuvant osimertinib (an EGFR inhibitor that is given as a tablet) and chemotherapy prior to surgery. However, clinical trial results are needed to see if this is beneficial.

What is adjuvant immunotherapy, and how does it differ from neoadjuvant?

Adjuvant effectively means after surgery, whereas neoadjuvant means before surgery. Adjuvant immunotherapy is immunotherapy that is given after surgery, rather than before.

In some circumstances, rather than giving any type of chemotherapy and/or immunotherapy before, the patients and their team of oncologists and surgeons might think it is best to proceed straight away to a surgical operation to remove the lung cancer, and then - after the cancer has been examined by pathologists - consider the benefit of adjuvant treatment. This adjuvant treatment will take place after surgery.

Classically, patients have been offered adjuvant chemotherapy because it has led to a small, but significant, increase in the chances of curing lung cancer after surgery.

More recently, the IMpower010 and the PEARL trial studies have shown that, for some types of immunotherapies (such as, atezolizumab and pembrolizumab, respectively), there are improved outcomes for patients who receive adjuvant immunotherapy for approximately about a year after surgery. In these circumstances, patients were offered their normal adjuvant chemotherapy for approximately four cycles worth of treatment (three weekly treatments), as well as a type of immunotherapy (potentially, atezolizumab or pembrolizumab) that were taken for approximately a year afterwards. Again, these patients had to come to hospital to have their treatments, intravenously, every three weeks.

It is important to know that both treatments (neoadjuvant and adjuvant) are not usually given to a same patient; a patient usually has one treatment or the other. However, there are a number of clinical trials currently investigating the use of both neoadjuvant and adjuvant immunotherapy for the same patient.

Does adjuvant therapy have advantages over neoadjuvant immunotherapy?

Obviously, with adjuvant therapy, a patient can undergo surgery straight away and then have immunotherapy afterwards. The benefit of this is that, when the surgeon examines the patient’s scans before surgery, the surgeon can determine at that exact moment if there is a high chance of removing the cancer. If so, then the surgeon can proceed straight to the operation without delay.

This is different with neoadjuvant immunotherapy and chemotherapy, as patients have chemotherapy and immunotherapy for approximately nine weeks before having surgery. Overall, patients benefit from this approach, but there is a small number of patients, where their cancer can unfortunately grow a bit bigger despite having immunotherapy and chemotherapy neoadjuvantly. This can then complicate surgery - and even, in some circumstances, mean that surgery is not possible.

Overall figures from the CheckMate 816 study show that neoadjuvant chemotherapy and immunotherapy is beneficial for patients, particularly for patients with immunogenic tumours (tumours that have high levels of a marker called PDL1). Yet, there may be some patients who benefit less, potentially patients with a low PDL1 test score, where having a long period of neoadjuvant chemotherapy and immunotherapy prior to surgery means that there is a potential risk of the cancer becoming more advanced before the patients actually get to undergo surgery.

Head on over to the second part of this series of articles on immunotherapy for lung cancer to find out about consolidation therapy and the use of immunotherapy for lung cancer in the metastatic setting.

If you require immunotherapy treatment for lung cancer, do not hesitate to book an appointment with Dr Crispin Hiley via his Top Doctors profile today.