Stage 4 Lung Cancer: Targeted therapy & Immunotherapy. Which to Start?

• Not all lung cancers are of the same type, stage or treated similarly.

In a nutshell…

A. Targeted therapy

For stage 4 lung adenocarcinoma (subset of NSCLC), further testing of EFGR and EML4-ALK mutation are routinely done in Malaysia.

ROS1 rearranged mutation driver testing is not routinely done although targetable treatment is available.

Those with detected mutation/ presence of oncogenic driver mutation will benefit from targeted therapies (gefitinib, erlotinib, afatinib, osimertinib, crizotinib, ceritinib, alectinib).

B. Immunotherapy

Patients without oncogenic mutation (EGFR, ALK, ROS1) driver is further tested on the percentage of PD-L1-expression in tumour +/- immune cells (some latest immunotherapy do not even need testing, eg. atezolizumab in 2nd line treatment).

Certain patients with positive PD-L1 expression in tumour cells will benefit from immunotherapy treatment (pembrolizumab, nivolumab, atezolizumab, avelumab).

I

Patients with advanced nonsquamous NSCLC that had progressed during or after platinum-based chemotherapy, overall survival was longer with nivolumab than with docetaxel. (Borghaei H, 2015)

II

Pembrolizumab prolongs overall survival and has a favourable benefit-to-risk profile in patients with previously treated, PD-L1-positive, advanced non-small-cell lung cancer. (RS Herbst, 2015)

The subgroup analysis of the above two large phase 3 studies showed no improvement in overall survival in patients with positive oncogenic mutation driver (EGFR) treated with immunotherapy.

Conclusion

In current practice:

• Patients with positive oncogenic mutation driver (EGFR, ALK) are treated with targeted therapy.
• Patients with positive oncogenic mutation driver and positive PD-L1 expression are treated with targeted therapy still (immunotherapy in later lines??).
• Patients with negative oncogenic mutation driver and positive+high PD-L1 expression are treated with immunotherapy.
• Patients with negative oncogenic mutation driver and positive+low PD-L1 expression are treated with immunotherapy+chemotherapy.
• Patients with negative oncogenic mutation driver AND negative PD-L1 expression are treated with chemotherapy.

Of course, the above are just simplistic view of the ever expanding treatments options available for advanced lung cancer.

Many studies are looking into optimal sequencing or combination of treatments, which could change the above once more results are made available.

UPDATE (28/7/2018)

Immunotherapy ineffective in EGFR-mutated non-small cell lung cancer (Lee, JTO, 2016)

The conclusion from the above study was that in EGFR-mutated non small cell lung cancer (NSCLC), immunotherapy (pembrolizumab, nivolumab and atezolizumab) did not improve survival when compared with palliative chemotherapy (docetaxel) in second-line NSCLC treatment.

Advertisement

• lung