Metastastatic NSCLC Flashcards
(8 cards)
Lung cancer epidemiology?
Lung cancer is the first for mortality rate and the second to breast cancer for incidence. In 2020 it caused almost 2 million deaths worldwide.
The main risk factor is smoking as 80/90% of cases are caused by smoking. Although people who never smoke may still develop lung cancer due to genetic alterations.
Different types of lung cancer? Main differences?
There are two main times : small cell lung cancer and non small cell lung cancer.
NSCLC is divided into adenocarcinoma (most common), squamous cell carcinoma and large cell carcinoma.
Adenocarcinoma is more peripheral while SCLC and SCC are more central, hilar.
Also adenocarcinoma is positive for TTF1 marker while SCC for P40 or P63.
Staging of lung cancer?
- Stage 1 is characterised by very small primary tumors (<4 cm), without lymph node involvement in the mediastnum.
- Stage 2 can present some lymph node involvement (it can be N1) and the dimensions of the primary tumor is intermediate (between 4 and 7 cm).
- Stage 3 can present a very big primary lesion (> 5or 7 cm) or there can be a small primary tumor but with the involvement of mediastnal lymph node (N2).
- Stage 3 B: it is N3, meaning that the primary tumor is on one side while the lymph nodes are on the opposite side, so there’s a controlateral lymph nodes involvement.
- Stage 3 C is characterised by big primary lesion and N3 involvement.
There are two diferent types of stage 4:
stage 4 A and stage 4 B. We have the former case if the
metastatc lesion is in the thorax or if there’s only one extra thoracic metastasis (for example one hepatc lesion), if there are multple extra thoracic lesions we have a stage 4B lung cancer.
Most common metastatic sites for lung cancer? When are patients diagnosed?
Bones, brain and adrenal glands.
More than half of lung cancer patients are diagnosed when already in metastatic disease. Stages 1,2 and 3A,3B are resectable, maybe with some neoadjuvant therapy.
3C is not resectable.
Therapy for metastatic lung cancer?
Chemotherapy has been the only strategy for many years. The best approach is using platinum based agents such as cisplatin. Now we also associate it with gemcitabine, paclitaxel, docetaxel.
With combination therapy we expect to observe a 30% reduction of the tumor in patient.
In NSCLC the targets of therapy are 10. In order to prescribe precise target therapy we take into account 9 targets, and the remaining one is to prescribe immunotherapy.
9 actionable mutations are for example EGFR, ALK, ROS1, BRAF, MET, RET, HER2, KRAS G12C and NTRK. If any of these are present we can use a targeted drug like osimertinib for EGFR.
1 immune target is for example PD-L1 expression.
T cells need 2 signals to be activated : T cell receptor needs to recognize a tumor antigen though the CD3 complex and CD28 and T cell binds to B7 on APC which activated the T cell. Cancer used PD-L1 to bind to PD-1 on the T cells inhibiting both signals that should activate the immune system. Also CTLA-4 competes with CD28 with B7, so if it binds there is no stimulation .
So in other words we can use anti PD1 or anti PD-L1 drugs like prembrolizumab or nivolumab to block that interaction and we can use drugs like ipilimumab to block CTLA-4.
Treatment choices based on PD-L1 levels?
If PD-L1 level is more than 50% than only immunotherapy with pembrolizumab for example with a very strong response.
If PD-L1 is between 1 and 49% we use chemo+immuno. Lik
If less than 1% we use chemo+dual immuno (PD1+CTLA4). Like platinum, premetrexed if adeno, paclitaxel in SCC plus pembrolizumab.
Patents with high PDL1 expression are 25%, the remaining 75% have an expression lower than the cutof (50%). Mono immunotherapy has been revolutonary in oncology.
Targeted therapy vs immunotherapy in NSCLC?
40–45% of NSCLC patients have a targetable mutation.
• In Italy, only 25% receive targeted therapy in first-line due to reimbursement limitations.
• The rest get it in second or third line depending on trial data and AIFA approval.
• Targeted therapies are not the same as immunotherapy. Most target-positive tumors don’t respond well to immunotherapy — except KRAS and BRAF (more common in smokers).
Different targeted therapy?
EGFR : 15% of NSCLC. Treatment with EGFR TKI showed 70% response rate. First generation TKI Gefitinib is used but more than 50% of patient acquire resistance to it therefore second generation EGFR TKI were created like Osimertinib.
ALK : 4% of NSCLC. Crizotinib is the first gen drug with a response rate of 70%. Newer generation like alectinib can be used to especially to avoid brain metastasis as crizotinib has poo brain penetration.
ROS-1 : Crizotinib or Entrectinib.
NTRK : Entrectinib has good response around 65%.
BRAF : 2% of cases, Dabrafenib+Trametinib is used.
In second line :
MET : 2% of cases, mainly affects old patients. Drugs include Tepinib and Capmatinib.
RET : 2% of cases. Paralsetinib and Selpercatinib.
HER2 : transtuzumab and deruxtecan.
KRAS : Sotorasib.
