Immuno-oncology drugs set out to conquer early stage cancer

ranging from lung cancer, breast cancer, to bladder cancer

Indications are being expanded to early treatment of various cancer types... increases possibility of surgery and reduces risk of metastasis and recurrence

Opdivo the first to obtain an indication as neoadjuvant therapy in NSCLC

Tecentriq, Keytruda, and Imfinzi also target early-stage lung cancer

Pic of Opdivo, Keytruda, Tecentriq, Imfinzi

The use of immuno-oncology drugs has advanced to the frontline of early-stage cancers.

 

This is because data has demonstrated that the use of immuno-oncology drugs in the early stages increases the possibility of surgery and reduces the possibility of metastasis and recurrence.

 

Following their use in the field of non-small cell lung cancer (NSCLC), immuno-oncology drugs are evaluated to be paving the way for early treatment in difficult-to-treat cancer types such as melanoma, bladder cancer, esophageal cancer, and breast cancer.

 

BMS and Ono Pharmaceutical’s anti-PD-1 immunotherapy Opdivo (nivolumab) has recently received approval for use in early-stage NSCLC.

 

The Ministry of Food and Drug Safety approved the drug in combination with platinum-based chemotherapy for ‘resectable (tumor size larger than 4cm or benign lymph node) on the 26th of last month.

 

With the approval, Opdivo became the first immuno-oncology drug allowed for use as adjuvant therapy in early-stage, resectable lung cancer patients.

 

Even with the addition of targeted anticancer drugs, Opdivo is the only drug that can be used as neoadjuvant therapy.

 

Previously, Tagrisso, an EGFR-targeted treatment, was approved as an adjuvant treatment in NSCLC.

 

The Phase III CheckMate-816 trial(ONO-4538-55), which became the basis for the approval, enrolled patients with stage IB-IIIA NSCLC to compare Opdivo+chemotherapy with chemotherapy monotherapy.

 

Its primary efficacy endpoint was event-free survival (EFS) and pathologic complete response (pCR) rate as assessed by the blinded independent central review (BICR).

 

The secondary efficacy endpoint was overall survival (OS) and major pathologic response (MPR), and time to death or distant metastases.

 

Results showed that in patients receiving Opdivo+chemotherapy, the median EFS was 31.6 months, decreasing the risk of relapse or death by 37% compared to 20.8 months of patients treated with chemotherapy alone.

 

The pCR was 24% in the Opdivo group, and 2.2% in the control group.

 

While the data are still immature, favorable early overall survival (OS) results were observed with Opdivo in combination with chemotherapy.

 

In the interim analysis, Opdivo+chemotherapy reduced the risk of death by 43%.

 

Further analysis will be conducted in the future as the data is yet to reach statistical significance.

 

Compared to how 83% of the patients that received treatment with Opdivo+chemotherapy survived after 2 years, the survival rate of those that only received chemotherapy was 71%.

 

Also, 83% of the patients who received Opdivo+chemotherapy received operations, compared with the 75% in chemotherapy-treated patients.

 

Rates of Grade 3-4 treatment-related adverse events were similar even with the addition of Opdivo to chemotherapy versus chemotherapy alone (34% vs.

 

37%).

 

Immuno-oncology competition extends to early-stage lung cancer In addition to Opdivo, other immuno-oncology drugs are also challenging the market.

 

Companies are conducting trials on Keytruda, Imfinzi, and Tecentriq to verify their efficacy as adjuvant or neoadjuvant therapy.

 

In October last year, the FDA approved Roche’s Tecentriq (atezolizumab) as adjuvant treatment in patients with stage II to IIIA NSCLC whose tumors have PD-L1 expression on ≥ 1% of tumor cells.

 

In Europe, the indication was expanded for patients whose tumors have a PD-L1 expression ≥ 50% based on the interim analysis that showed a high effect in that patient group.

 

Interim analysis results showed that adjuvant Tecentriq resulted in a 57% reduction in the risk of disease recurrence or death compared with best supportive care (BSC) in patients with stage II to IIIA NSCLC with PD-L1 expression of 50% or higher.

 

Based on such findings, Roche is also planning to expand Tecentriq’s indication in Korea within the year.

 

MSD’s Keytruda (pembrolizumab) is aiming to expand its indication as adjuvant therapy in patients with early-stage NSCLC (Stage IB-IIIA) regardless of PD-L1 expression.

 

Interim analysis results of the Phase III KEYNOTE-091 study that was presented earlier this year showed that Keytruda significantly improved disease-free survival (DFS), which was one of the primary efficacy endpoints, and reduced risk of recurrence or death by 24% compared with placebo.

 

The median progression-free survival [PFS] of the Keytruda-treated group was 53.6 months and 42.0 months for the placebo group.

 

AstraZeneca’s Imfinzi (durvalumab) also presented positive results as a neoadjuvant therapy before surgery based on the interim results from the Phase III AEGEAN trial that was presented in July.

 

The trial evaluated Imfinzi in combination with neoadjuvant chemotherapy as perioperative treatment for patients with resectable Stage IIA-IIIB NSCLC, and results showed that the combination therapy significantly improved pathologic complete response (pCR) compared to neoadjuvant chemotherapy alone.

 

However, other primary and secondary efficacy endpoints of the trial, including event-free survival (EFS), disease-free survival, overall survival, etc.

 

To esophageal cancer, bladder cancer, and melanoma...

 

use as early treatment expanded to various cancer types The entry of immuno-oncology drugs to early-stage cancer is not limited to NSCLC.

 

Opdivo demonstrated its efficacy as adjuvant therapy in melanoma, bladder cancer, and esophageal cancer as well.

 

Its indications are: ▲as adjuvant therapy in patients with lymph node involvement or metastatic Stage IIIB/C or IIII melanoma who have undergone complete resection; ▲as adjuvant therapy in patients with non-muscle-invasive bladder cancer (NMIBC) at high risk of recurrence after radical surgical resection ▲as neoadjuvant therapy for completely resected esophageal or gastroesophageal junction cancer in patients with residual pathologic disease who have received neoadjuvant chemoradiotherapy.

 

Moreover, study results that demonstrate Opdivo’s effect as adjuvant therapy in patients with Stage IIB-IIC melanoma, an earlier stage than the existing indications, were also presented recently.

 

Interim analysis results of CheckMate-76K that was presented last month showed that Opdivo as adjuvant therapy reduced the risk of recurrence or death by 58% versus placebo in patients with completely resected Stage IIB or IIC melanoma.

 

Opdivo’s 12-month recurrence-free survival (RFS) was 89% versus 79% for the placebo group.

 

Keytruda also obtained an indication as adjuvant therapy in patients with Stage IIB or IIC melanoma who have undergone complete resection and renal cell carcinoma (RCC) with a high risk of recurrence following nephrectomy.

 

In triple-negative breast cancer (TNBC), Keytruda was approved as both adjuvant and neoadjuvant therapy.

 

In other words, in TNBC, Keytruda can be used in combination with chemotherapy as neoadjuvant treatment, and then continued as a single agent as adjuvant treatment after surgery.