Explaining immunotherapy to our patients with NSCLC
The days of chemotherapy in 2003
I have been treating lung cancer as a nurse practitioner for about 15 years. At the time I became involved in the management of lung cancer patients, treatment was simple. There were just a few chemotherapy options, which were generally quite toxic; however, given there were only a few drugs in the arsenal, the education for each patient was very similar: neutropenia, anemia, neuropathy, fatigue, nausea, and vomiting. The education was detailed, but similar for each patient. The mechanism of chemotherapy was to attack rapidly dividing cells, which in patient terms, meant that it would attack several healthy cells as well, resulting in these side effects.
But change was around the corner; during that time around 2003, we had a new epidermal growth factor receptor (EGFR) inhibitor, gefitinib, in clinical trials. It transpired that it worked very well, especially in Asian female never-smoking patients, though it caused a rash. We didn’t know why that subset of patients responded so well. Plus, I remember thinking that this was such a new and different treatment. The education for this was brand new back then and so different from our traditional chemotherapy. This was the first time we discussed receptors, and the blockade of internal cellular signaling with patients. Also, we discussed the difference between routine chemotherapy toxicities versus EGFR toxicities, which focused more around rash and diarrhea.
Fast forward to 2017-2018
We now have chemotherapy, targeted therapies, and immunotherapy drugs. The drugs are used as single agents or sometimes in combinations of chemotherapy and immunotherapy. Patient education has really changed from a one-size-fits-all approach, to now tailoring education based on the mechanism of action of the treatment. In these times of the internet, patients are knowledgeable about treatments, but many times, may have false or misguided information. Advanced practice providers, such as pharmacists, physician assistants, and nurse practitioners, as well as oncology nurses, are often positioned to consent patients for treatment and describe therapy to them. This process not only involves discussions about the side effects, but the mechanisms of action.
Unless the patient has an extensive background in molecular biology, it is unlikely that they will understand terms like 'programmed death-ligand' or 'dendritic cells'. It may be hard for those of us in oncology, especially those providers who speak frequently on the topic to other oncology healthcare providers, when we are accustomed to using medical terminology. However, when speaking to patients, we must break down the mechanism of action of immunotherapy into everyday terminology for them to understand.
Patient education has really changed from a one-size-fits-all approach, to nowadays tailoring education based on the mechanism of action of the treatment.
Explaining the mechanism of action
When discussing treatment for cancer, patients are used to calling it “chemotherapy”. It is important to explain that while their treatment is called immunotherapy rather than chemotherapy, the goal is the same; it is to kill cancer cells and keep their cancer from growing and spreading. Then, we need to expand on this by introducing the idea that instead of killing many healthy cells in addition to the cancer cells, immunotherapy works to assist your own immune system to kill the cancer cells. Next, this can lead into further conversation with the patient about how this process works.
Again, in the spirit of keeping the conversation at a level of understanding for the average patient, the provider can describe how cancer cells hide themselves or evade the patient’s own immune system by expressing receptors on their surface that turn off nearby T-cells. Sometimes the provider can elaborate on this interaction depending on the patient’s current knowledge level or interest in further understanding the mechanism of action. It is helpful to understand this part, because that can lead to an understanding of how the drug blocks the receptor or the ligand in order to leave the T-cell turned on and, thus, available to attack the cancer cells.
It can be difficult to explain this complicated idea in understandable terms to patients. One way of doing so is to use simple real-life analogies to explain the interactions between immunotherapy drugs and the cancer. For example, you can tell a patient that the cancer suppresses the immune system like a person might shoot a tranquilizer into a bear to put it to sleep (see image below). Drugs like checkpoint inhibitors essentially stop the tranquilizer effect, thus allowing the bear (the immune system) to be awake and attack (the cancer). In addition, understanding the mechanism of action can be helpful because it may help patients understand the unique toxicities associated with immunotherapy drugs.
The drugs and side effects
There are currently three immunotherapy drugs approved in the United States for the treatment of non-small cell lung cancer (NSCLC): Programmed cell death protein 1 (PD-1) inhibitors nivolumab and pembrolizumab, and the programmed death-ligand 1 (PD-L1) inhibitor, atezolizumab. There is also a pending indication within the NCCN guidelines for durvalumab, another PD-L1 inhibitor given in the locally advanced, consolidation setting of NSCLC.
Both nivolumab and atezolizumab are approved for use in metastatic NSCLC after failure of platinum-based chemotherapy, regardless of PD-L1 score[2-4]. Pembrolizumab is approved in three different settings: first line for PD-L1 score 50% or higher, second line for PD-L1 score 1% or higher, and first line in combination with pemetrexed and carboplatin chemotherapy, regardless of PD-L1 score [5-7]. Durvalumab is under consideration for approval after chemotherapy plus radiation in stage III NSCLC as a consolidation treatment, given every 2 weeks for up to 12 months . For further detail, see the table below:
|Drug||Indications||Mechanism of action||Dosing|
|Nivolumab||Metastatic NSCLC: After failure of platinum-based chemotherapy regimen, independent of PD-L1 status.|
|240mg IV every 2 weeks|
|200mg IV every 3 weeks|
|Atezolizumab||Metastatic NSCLC: After failure of platinum-based chemotherapy regimen, independent of PD-L1 status||PD-L1 inhibitor||1200mg IV every 3 weeks|
|Durvalumab*||Does not yet have an indication. Was studied in the setting of Stage III NSCLC, given after completion of chemotherapy plus radiation, in patients who were not progressing, taking the drug every 2 weeks for up to 12 months.||PD-L1 inhibitor||---|
The side effects of immunotherapy drugs are also very different from chemotherapy drugs. While the common toxicities will still align with chemotherapy as far as fatigue and nausea, there are much fewer grade 3 or 4 fatigue and nausea events than are associated with chemotherapy. However, there are the unique immune-mediated toxicities associated with these immunotherapy agents that are not generally seen with chemotherapy. These include, but are not limited to:
- Pneumonitis (seen more frequently in NSCLC patients as opposed to other tumor types)
There are several other immune-mediated toxicities that can occur including several neurological, hematological, and cardiac toxicities.
The patient experience
Explaining these side effects to patients starts with reminding them that they are different from traditional chemotherapy side effects, especially since many patients have already had chemotherapy. It is also important to tell them that these toxicities are often life-threatening, so reporting symptoms immediately is very important. They should immediately report:
- Increase in shortness of breath or nagging frequent cough
- Significant diarrhea associated with abdominal pain, cramping, or blood/mucus in the stool
- Heart palpitations and severe malaise
- Significant rash with hives or significant itching with rash
- Any other symptoms that seems concerning to the patient
The nephritis and hepatitis often will only be found on the lab reports and there may not be physical symptoms associated with them. Moreover, I have found that in my only two cases of colitis, both patients, who were reliable and knowledgeable, did not report the symptoms until they were due back for the routine visit. Both patients had been educated about the potential for colitis, but both had assumed that they had eaten something bad and their diarrhea, abdominal pain, and weight loss were due to the bad food rather than being a red flag for colitis.
Immunotherapy is less likely than chemotherapy to affect patients in their daily living. For example, they generally will not have to plan a 'weekend to recover' like they do after receiving platinum-based chemotherapy regimens. They are less likely with immunotherapy to experience the daily life-altering toxicities such as nausea, loss of appetite, complete hair loss, and severe fatigue. This is a benefit usually for patients receiving immunotherapy; it gives them a chance to live day to day without the burden of the chemotherapy side effects.
It is also important to tell [patients] that these toxicities are often life-threatening, so reporting symptoms immediately is very important.
Patients' optimistic expectations of treatment with immunotherapy is also a newer concept to grasp. Here in the USA, there has been a dramatic increase in product-to-consumer advertising when it comes to these drugs. Two of the immunotherapy drugs approved for treatment in NSCLC have been regularly featured in television commercials in primetime markets targeting large audiences. This is the first time that an oncology therapeutic drug (non-supportive care drug) has been advertised as a television commercial. One drug commercial shows healthy men and women telling stories of positive experiences with the drugs. Another commercial depicts men and women living active and happy lives while on these drugs. This advertising has lead to patients coming in and asking for this drug with the hope and expectation that there will be no side effects and they will have great responses. It has created, in some instances, a crossroads where doctors and nurses must explain why a patient may not be eligible, or to be transparent about the actual response rates and potential for toxicities.
Explaining the mechanisms of action and the unique side effects of immunotherapy to patients can raise significant challenges for oncology healthcare providers. Learning to speak in terms that patients can understand and identify with, can facilitate the education and hopefully help the patients report their symptoms in a timely manner. We must all stay abreast of the latest drug approvals and their toxicity management and strive to educate our patients with the best of our abilities.
- NSCLC. Available at www.nccn.org/professionals/physician_gls/PDF/nscl.pdf. [Accessed at 30 Jan 2018; Log-in required]
- Borghaei H et al. Nivolumab versus docetaxel in advanced non-squamous non-small-cell lung cancer. N Engl J Med 2015; 373: 1627-1639.
- Brahmer J et al. Nivolumab versus docetaxel in advanced squamous-cell non-small-cell lung cancer. N Engl J Med 2015; 373: 123-135.
- Fehrenbacher L et al. Atezolizumab versus docetaxel for patients with previously treated non-small-cell lung cancer (POPLAR): a multicentre, open-label, phase 2 randomised controlled trial. Lancet 2016; 387: 1837-1846.
- Herbst R et al. Pembrolizumab versus docetaxel for previously treated, PD-L1-positive, advanced non-small-cell lung cancer (KEYNOTE-10) : a randomised controlled trial. Lancet 2016; 387: 1540-1550.
- Reck M et al. Pembrolizumab versus chemotherapy for PD-L1 positive non-small-cell lung cancer. N Engl J Med 2016; 375: 1823-1833.
- Langer CJ et al. Carboplatin plus pemetrexed with or without pembrolizumab for advanced, non-squamous non-small cell lung cancer : a randomised, phase 2 cohort of the open label KEYNOTE-21 study. Lancet Oncol 2016; 17: 1497-1508.
- Antonia SJ, Villegas A, Daniel D, et al. Durvalumab after chemotherapy in stage III non-small-cell lung cancer. N Engl J Med 2017; 377: 1919-1929.