‘Tecentriq needed for early lung cancer and post-operative adjuvant therapy’

Non-small cell lung cancer (NSCLC) has been one of the areas the treatments of which have not drawn much attention. The biggest reason: finding lung cancer patients in the early stage was difficult.

According to national cancer statistics, about 45 percent of Korean lung cancer patients are stage 4 patients. That also explains why most clinical trials for targeted agents and immunotherapies target stage four patients.

In contrast, clinical trials are rarely conducted for NSCLC, and it is also challenging to find significant data regarding its patients and treatments.

Against this backdrop, Roche’s Tecentriq (atezolizumab) deserves attention as it showed significant clinical improvement among clinical trials conducted on patients without target genes for the first time worldwide.

Korea Biomedical Review met with Professor Hong Min-hee of the Oncology Department at Yonsei Cancer Center to learn about the reality facing the early-phase NSCLC treatment and the clinical value of Tecentriq that won approval as postoperative adjuvant therapy for the first time.

Question: What are the chances of recurrence after surgery in NSCLC?

Answer: That varies depending on the disease’s phase, and there is also a difference between the past and present data. Besides, there are differences between the Western and Eastern data. The recurrence rates are 40 percent in phase 2, 50 percent in phase 2, and 75 percent in phase. I guess the treatment environment has somewhat improved in the past, pulling down the recurrence rate a little. The recurrence rate of Korean patients is reportedly lower than that of Western patients. Still, about half of phase 3 patients experience recurrence.

Q: As diagnostic technology develops, lung cancer treatment seems to be made earlier than phase 4.

A: That’s why patients anticipate complete remission (CR). However, the CR rate can’t help being low for phase 4 patients. Nevertheless, patients diagnosed early can receive treatment with the goal of complete recovery, and their expectations are also high.

Q: Six months have passed since atezolizumab won approval as postoperative adjuvant therapy in NSCLC for the first time among immunotherapies.

A: As the drug has yet to receive insurance benefits for the related indication, we use it in a small number of patients who can afford it financially and are fit for the therapy. If registered on the reimbursement list, atezolizumab will likely be the option for postoperative adjuvant therapy without hesitation.

Q: What are the clinical effects of atezolizumab as postoperative adjuvant therapy?

A: According to data, when we use atezolizumab in phase 2-3A NSCLC patients with PD-L1 expression rate of 50 percent or higher and after treating them with complete resection and platinum-based chemotherapy, the hazard ratio (HR) of recurrence or death (disease-free survival or DFS) was 0.43 compared to best supporting cure (BSC).

They say it is quite successful if the ratio is lower than 0.7. However, atezolizumab showed an HR of 0.6 in patients with a PD-L1 expression rate of 1 percent or higher and lower than 0.5 in patients with a PD-L1 expression rate of 50 percent or higher. Considering that HR in immunotherapies’ clinical trial on phase 4 patients is around 0.6, the 0.43 figure is significant clinically and statistically.

Besides, benefits in DFS were consistently observed in most subgroups, including treatment records and disease phases. However, in the case of overall survival (OS), atezolizumab did not reach the median value in the follow-up monitoring of 32.8 months.

Q: Why do you look at DFS in early lung cancer?

A: Patients who received the operation have no diseases remaining and are in a disease-free status. However, if these patients die or experience recurrence, we call it disease-free survival (DFS). It is a similar concept to progress-free survival (PFS).

In addition, it is not easy to quickly confirm effects, including OS, in the early stage. We must invest five to 10 years in confirming OS. Accordingly, we use DFS as a proxy indicator. A 2014 study published on LANCET also found DFS is identical to OS to a certain extent as the NSCLC adjuvant therapy.

Q: Can you expect benefits by administering existing immunotherapies used in metastatic or recurrent patients in early lung cancer patients?

A: There is no fixed answer. Theoretically, however, it is better to use immunotherapies before the operation than after it and when the tumor’s volume is smaller than after it gets bigger. Accordingly, I expect immunotherapies in patients in operable disease phases to be far more helpful for reinvigorating the immune system.