November is lung cancer awareness month. Lung cancer has always been one of the most prevalent cancers in Belgium, and also the one with the highest death toll in absolute numbers. However, the advent of immune therapy in 2016 brought about huge changes and improvement in overall survival. In the most common type of lung cancer, non-small cell lung cancer or NSCLC, five-year survival is almost doubled thanks to immune therapy drugs. Response rates are almost 5 times those of chemotherapy, and mortality risk decreases by 38%, And immune therapy comes with considerably fewer adverse side effects compared to chemotherapy (31.2% vs 53.3%).1,2
Presently, around 1 in every 3 new lung cancer diagnoses in Belgium is treated with immune therapy, either as monotherapy or in combination with other treatments.3
Recently, the results of the Keynote-024 study were presented, a long-term large scale trial concerning the use of immune therapy in advanced and/or metastasized NSCLC. Professor Johan Vansteenkiste, respiratory oncologist at UZ Leuven explains what the trial was about and what the results are. “Included patients presented lung tumours with a high PD-L1 count, a protein on the cell membrane that serves as a reliable indicator to predict the probability of success of immune therapy. Around 1 in 3 NSCLC tumours have a high PD-L1 expression and are therefore suitable for immune therapy. Well, the results for this group of patients exceed expectations. In treatment-naive patients immune therapy almost doubles the 5-year survival compared to chemotherapy (31.9% vs. 16,3%). And mortality risk decreases by 38% in metastasized NSCLC.”
Vansteenkiste points out that long-term results are even more promising. Patients who have been treated with immune therapy for 2 years show a 5-year survival of 81.4%, and around half of these patients have not resumed treatment. “Furthermore, patients who were treated with immune therapy showed fewer negative side effects than chemotherapy-patients (31.2% vs. 53.3%), and these side effects are less frequent than those associated with chemotherapy. Most common side effects with immune therapy are inflammations of the skin, liver, thyroids, lungs or intestines.”1,2
According to the Belgian Cancer Registry, over 8,000 new lung cancer patients are diagnosed annually, making it the 3rd most prevalent cancer in Belgium. There are two main forms of lung cancer: non-small cell lung cancer (NSCLC), which occurs in 85% of cases, and small cell lung cancer (SCLC) that affects the other 15%. In 2016, 6325 people died as a result of lung cancer in Belgium. Lung cancer used to come with a bad prognosis, and in men it is the most deadly cancer in Belgium. In patients who were diagnosed with advanced lung cancer -70% of all cases- the 5-year survival was only 1%.3
The advent of immune therapy in 2016 brought about radical changes. Professor Vansteenkiste is enthusiastic about the new treatment options offered by immune therapy, and it has grown to be the standard of care in the treatment of metastasized lung cancer. “If we extrapolate the data from the cancer registry, it is estimated that 1 in 3 new lung cancer cases are treated with immune therapy, which comes down to around 3,000 patients for 2020. Just like with any other treatment, there is always a chance that a patient will not respond to treatment, but when a response does occur, it tends to be long-lasting. This is the result of a unique quality of immune therapy: we now have a cancer treatment that, just like the human immune system, has a type of memory function. As a result we now see a growing group of patients with much improved survival rates.”
Keynote-024 is an open randomized phase III study comparing immune therapy (pembrolizumab) with chemotherapy in stage 4 NSCLC with previously untreated metastases and a PD-L1 expression in 50% or more of tumour cells. In total, 305 patients were randomly assigned in a 1:1 ratio to either receive pembrolizumab (200 mg intravenously every 3 weeks until progression or intolerable toxicity), or one of five platinum-based chemotherapy options. These were: carboplatin plus pemetrexed, cisplatin plus pemetrexed, carboplatin plus gemcitabine, cisplatin plus gemcitabine of carboplatin plus paclitaxel (4-6 cyes). In case of progression, patients had the option to receive pembrolizumab.
Patients with a genetic condition that stimulates cancer (eGFR mutation, translocation of the ALK-gene), untreated brain metastases, who were treated with glucocorticoids or immune suppressants were excluded. Over the long term of this trial, no new safety concerns came to light regarding pembrolizumab. In the pembrolizumab-arm of the trial, 31.2% of patients experienced treatment-related adverse events graded 3 to 5. For the chemotherapy-arm this was 53.3%.
2: J.R. Brahmer et al. KEYNOTE 024 5 Year OS Update: First Line Pembrolizumab vs Platinum Based Chemotherapy in Patients With Metastatic Non Small Cell Lung Cancer and PD L1 Tumor Proportion Score 50%. Oral presentation at the European Society for Medical Oncology® (ESMO) Sept 19-21, 2020 (virtual format).