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Table 3 . Approved targeted and immune therapies used for NSCLC Target Drug Indication Targeted therapies EGFR Gefitinib Treatment of patients with locally advanced or metastatic NSCLC with EGFR mutations Erlotinib
Afatinib
Osimertinib
First- or subsequent-line therapy in patients with locally advanced or metastatic NSCLC EGFR mutations
First- or subsequent-line therapy in patients with locally advanced or metastatic NSCLC EGFR mutations
First-line treatment of patients with locally advanced or metastatic NSCLC with EGFR mutations , and treatment of EGFR T790M mutation-positive NSCLC Adjuvant therapy after NSCLC tumour resection with EGFR mutations
ALK Crizotinib Treatment of patients with ALK-positive locally advanced or metastatic NSCLC Ceritinib Alectinib Brigatinib
Treatment of patients with ALK-positive locally advanced or metastatic NSCLC Treatment of patients with ALK-positive locally advanced or metastatic NSCLC Treatment of patients with ALK-positive locally advanced or metastatic NSCLC
Figure 7 . Scanning for disease .
Figure 7A . CT chest scan showed a spiculated lesion within the superior aspect of the right middle lobe , with a further 47mm lesion abutting the mediastinum .
Figure7B . PET scan confirmed presence of metastatic disease .
decision-making is more pragmatic than with NSCLC , with patients categorised into “ limited stage ” or “ extensive stage ”. Limited disease is confined to the chest . Limited-stage patients are generally treated with platinum-based chemotherapy and radiotherapy +/ - prophylactic cranial irradiation . Current best practice for patients with extensive-stage disease involves platinum-based chemotherapy combined with an ICI .
Radiation is considered in patients with bulky disease and to prevent or treat brain metastases . 19 Approved first- and subsequent-line targeted and immunotherapies are summarised in table 3 .
Palliative and supportive care
Patients with lung cancer can have a high symptom burden , depending on disease stage . Early palliative care involvement significantly improves outcomes and is considered best practice . 34
Treatment burden in lung cancer
Patients undergoing lung cancer treatment can experience significant treatment burden , particularly in terms of the impact of treatment and side effects on lifestyle and relationships . A person ’ s capacity to undergo treatment as well as the ability to navigate the complexities involved with the healthcare system are important factors to consider in ensuring that a treatment plan is manageable for the patient . 35
Suggestions to help reduce treatment burden include managing expectations ( especially regarding lifestyle changes they will need to make ), providing information on the required lifestyle changes to help with an easier transition to a life with treatment , and realistic advice on how to deal with their disease , and services to assist them . 35 Patients with lung cancer and their carers and families will need psychological support to help cope with
25 , 36 their diagnosis and treatment . Cancer Australia ’ s Lung Cancer Framework has been developed as a resource for health professionals and service providers who are involved in the care and treatment of people affected by lung cancer .
The five principles ( summarised in box 7 ) support evidence-based
approaches to improve the outcomes and experiences of people affected by lung cancer in Australia .
The Optimal Care Pathway series also covers lung cancer and describes the standard of care that should be available to all lung cancer patients in Australia . 19
CASE STUDIES
Case study one
MELISSA , 56 , presents to her GP with a five-week history of worsening shortness of breath on exertion . This is associated with a significant reduction in exercise tolerance , intermittent light-headedness and sharp chest discomfort . She has no fever , cough , weight loss or night sweats , and there is no history of recent long-haul travel or other deep vein thrombosis ( DVT ) risk factors . A recent COVID-19 swab was negative .
She has a background of asthma , anxiety and depression . Her regular medications include budesonide / formoterol , salbutamol and desvenlafaxine . There is no family history of cancer . There is a 10 to 15-pack year history of cigarette smoking , and Melissa consumes three standard alcoholic drinks per day .
On examination , Melissa is short of breath at rest but able to speak in full sentences . Oxygen saturations are 93 % on room air , heart rate is 103bpm and blood pressure is 154 / 93mmHg . There is decreased air entry to the right mid / lower zone with associated dullness to percussion .
An outpatient chest X-ray shows a large right pleural effusion with no mediastinal shift , and the left lung is clear . Melissa is referred to hospital and the pleural effusion ( 4L ) is drained . Cytology shows adenocarcinoma , TTF1 positive consistent with adenocarcinoma of the lung .
There is no evidence of any oncogenic driver , and PD-L1 TPS is greater than 70 %. When PD-L1 binds to another protein called PD-1 ( a protein found on T cells ), it keeps T cells from killing the PD-L1-containing cells , including the cancer cells .
A CT chest scan shows a 3.5 x 2.6 x 1.2cm spiculated lesion within the superior aspect of the right middle lobe , with a further 47mm lesion abutting the mediastinum ( see figure 7A ). PET scan confirms the presence of metastatic disease ( see figure 7B ). There is widespread lymph
Lorlatinib
node involvement and two metastatic deposits to the liver . Melissa is referred to the medical oncology team . Given her underlying metastatic disease , and the absence of an oncogenic driver mutation , she is started on combined chemo-immunotherapy ( carboplatin / pemetrexed / pembrolizumab ).
Following three months of treatment , a restaging PET scan shows an almost complete response to therapy
Treatment of patients with ALK-positive locally advanced or metastatic NSCLC ROS1 Crizotinib Treatment of patients with ROS1-positive advanced NSCLC
Entrectinib Treatment of patients with ROS1-positive advanced NSCLC
MET |
Tepotinib |
Provisional approval for treatment of patients with locally advanced or metastatic NSCLC |
|
|
with MET exon 14 skipping alterations |
Immune therapies
PD-1 |
Pembrolizumab |
Initial treatment of NSCLC |
|
|
Can be combined with chemotherapy or used as single agent |
Nivolumab
Second-line after progression on platinum-based chemotherapy or tepotinib First-line combination treatment with ipilimumab
PD-L1 |
Atezolizumab |
Second-line treatment of locally advanced or metastatic NSCLC after platinum-based chemotherapy or tepotinib Treatment of metastatic non-squamous type NSCLC in combination with bevacizumab and platinum-doublet chemotherapy Adjuvant treatment of early-stage NSCLC following complete resection and no progression adjuvant chemotherapy in patients with resected Stage II-III NSCLC and a PD-L1 TPS score of 50 % or more First-line treatment of extensive-stage SCLC in combination with etoposide and a platinum-based antineoplastic drug |
Durvalumab
Cemiplimab
Treatment of patients with locally advanced , unresectable NSCLC not progressed following chemoradiation therapy
First-line treatment of metastatic NSCLC or progressed after treatment with tepotinib
ALK = anaplastic lymphoma kinase , MET = mesenchymal-epithelial transition , NSCLC = non-small cell lung cancer , PD-L1 = programmed death ligand 1 , TKI = tyrosine kinase inhibitor Adapted from John et al 2020 37
Box 7 . Lung Cancer Framework : Principles for Best Practice is a national resource for health professionals and service providers involved in the care and treatment of people affected by lung cancer
• Principle 1 : Patient-centred care Patients with lung cancer and their carer ( s ) are the focus of best practice lung cancer care .
• Principle 2 : Timely access to evidence-based pathways of care Optimal care pathways are in place to support the timely diagnosis and staging of lung cancer , as well as appropriate treatment , supportive , follow-up and end-of-life care .
• Principle 3 : Multidisciplinary care An integrated team approach used across the lung cancer pathway to ensure that each patient ’ s individual treatment plan considers all relevant treatment and care options .
• Principle 4 : Coordination , communication and continuity of care All relevant health professionals , including GPs , provide coordinated delivery of lung cancer care across all services and settings , and along the cancer care pathway .
• Principle 5 : Data-driven improvements in lung cancer care Lung cancer data are collected , monitored and reviewed regularly to support continuous improvement in the delivery of best practice lung cancer care .
Source : Cancer Australia 2018 33
( see figure 8 ). Melissa has been on ongoing maintenance chemo-immunotherapy with pemetrexed / pembrolizumab for 1.5 years and is enjoying good quality of life .
Case study two
Clive , 65 , a lifelong non-smoker , presents with a two-month history of hoarse voice and shortness of breath on a background of previously good health . On examination , he is not in any respiratory distress , oxygen saturation is 98 % on room air and the chest is clear to auscultate .
A chest X-ray then CT scan , arranged as an outpatient , show a cavitating mass measuring almost 5cm in the left upper lobe of the lung , with enlarged lymph nodes in the mediastinum .
A bronchoscopy is performed , and biopsies confirm the lesion is an adenocarcinoma consistent with a primary lung cancer . There are no driver mutations identified , and PD-L1 is measured at greater than 1 %. An FDG PET scan confirms no evidence of any distant metastatic disease .
Clive ’ s case is discussed at a local multidisciplinary team meeting . Because of the size of the primary tumour and degree of lymph node involvement , his disease is staged as IIIa , meaning surgical resection is not the ideal option . It is decided he should proceed with combined chemo-radiotherapy . Clive is treated for six weeks with carboplatin / paclitaxel chemotherapy concurrent with radiotherapy . Following this he proceeds with consolidation immunotherapy with durvalumab .
Case study three
Lisa , 62 , presents to her GP with a fourmonth history of cough , with associated haemoptysis over the past two months . She had been experiencing intermittent night sweats and fatigue and has no history of shortness of