Roche's Tecentriq Becomes First Cancer Immunotherapy to Significantly Prolong Disease-Free Survival in Adjuvant Treatment of Resectable Early-Stage NSCLC

May 21, 2021 /BioonBIOON/ -- Roche recently announced the interim results from the Phase III IMpower010 study evaluating the anti-PD-L1 therapy Tecentriq (atezolizumab) for resectable early-stage (Stage IB-IIIA) non-small cell lung cancer (NSCLC). Data showed that in the overall randomized Stage II-IIIA NSCLC patient population, adjuvant treatment with Tecentriq following surgery and chemotherapy demonstrated a statistically significant improvement in disease-free survival (DFS) compared with best supportive care (BSC) (HR=0.79).The DFS benefit was particularly pronounced in the PD-L1-positive patient population (HR=0.66).。

The purpose of adjuvant therapy is to reduce the risk of recurrence and provide the best chance of cure.Nevertheless, approximately half of patients with stage I-III NSCLC ultimately experience disease recurrence following curative-intent treatment. Adjuvant platinum-based chemotherapy is currently the standard of care for patients with early-stage NSCLC (stage IB-IIIA) at high risk of disease recurrence after complete resection.Compared with observation, adjuvant platinum-based chemotherapy modestly improved the 5-year survival rate by 4–5%.Therefore, there is a significant unmet medical need for new adjuvant treatment regimens in this field.

Notably, this is the first phase III study to demonstrate that, compared with best supportive care (BSC), a cancer immunotherapy improves disease-free survival (DFS) in patients with resectable early-stage lung cancer. Meanwhile,Tecentriq is the first and only cancer immunotherapy to achieve positive Phase III results in the adjuvant treatment of early-stage lung cancer.

Dr. Levi Garraway, Chief Medical Officer and Global Head of Product Development at Roche, said: “These milestone Phase III data demonstrate for the first time that cancer immunotherapy can provide clinically meaningful improvement in adjuvant therapy for certain patients with early-stage lung cancer. These results lay the foundation for new approaches to treating early-stage lung cancer and bring us closer to our goal of providing effective and tailored treatment options for every person diagnosed with lung cancer.”

IMpower010 is a global, multicenter, open-label, randomized phase 3 study evaluating the efficacy and safety of adjuvant treatment with Tecentriq or BSC following surgical resection and up to 4 cycles of cisplatin-based adjuvant chemotherapy in patients with stage IB–IIIA NSCLC (UICC 7th edition). In this study, 1,005 patients were randomized in a 1:1 ratio to receive up to 16 cycles of Tecentriq or BSC. Primary endpoint: Investigator-assessed disease-free survival (ivDFS) in the PD-L1-positive stage II–IIIA population, the all-randomized stage II–IIIA population, and the intent-to-treat (ITT) stage IB–IIIA population. Key secondary endpoints include: Overall survival (OS) in the overall study population and the ITT stage IB–IIIA NSCLC population. Results showed:

——InTumorIn patients with stage II-IIIA NSCLC and PD-L1 expression ≥1%: When Tecentriq is used as adjuvant therapy after surgery and chemotherapy, compared with BSC, it willThe risk of disease recurrence or death was significantly reduced by 34%.(HR = 0.66; 95% CI: 0.50–0.88; p = 0.004). In this patient population,Median DFS was not reached in the Tecentriq treatment group, while it was 35.3 months in the BSC group.。

——Among all randomized patients with stage II-IIIA NSCLC: After a median follow-up of 32.2 months, compared with BSC, Tecentriq will21% reduction in the risk of disease recurrence or death(HR=0.79; 95% CI: 0.64-0.96; p=0.02). In this patient population,Compared with the BSC group, median DFS in the Tecentriq group was prolonged by 7 months (42.3 months vs. 35.3 months).

IMpower010 Clinical Data (Click image to view enlarged version)

In this study, the safety data for Tecentriq were consistent with its known safety profile, with no new safety signals identified. In the overall study population, adverse events (AEs) occurred in 92.7% of patients in the Tecentriq group and 70.7% in the BSC group; Grade 3 or 4 AEs occurred in 21.8% of patients in the Tecentriq group and 11.5% in the BSC group. Grade 5 AEs occurred in 0.8% of patients in the Tecentriq group. As expected, with up to one year of adjuvant therapy following chemotherapy, Tecentriq resulted in a higher incidence of adverse events compared with BSC.

Follow-up in this study will continue to allow for a planned analysis of disease-free survival (DFS) in the overall intention-to-treat (ITT) population, including stage IB patients for whom data had not yet reached the threshold at the time of this analysis; overall survival (OS) data were immature at the time of the interim analysis.

Lung cancer is the leading cause of cancer-related mortality worldwide. Approximately 1.76 million people die from the disease annually, which translates to over 4,800 deaths globally every day. Lung cancer can be broadly classified into two main categories: non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC). NSCLC is the most common type, accounting for approximately 85% of all cases. Currently, approximately half of patients with early-stage lung cancer still experience disease recurrence following surgery. Early intervention before the cancer spreads may help prevent recurrence and provide patients with the best chance of a cure.

Previously, Tecentriq has demonstrated clinically meaningful benefits across various types of lung cancer and is currently approved in the United States for five lung cancer treatment indications: (1) Tecentriq is the first cancer immunotherapy approved for the first-line treatment of adult patients with extensive-stage small cell lung cancer (ES-SCLC), in combination with chemotherapy (carboplatin plus etoposide); (2) it has four treatment indications for NSCLC, administered as monotherapy or in combination with targeted therapy and/or chemotherapy. Tecentriq offers three dosing regimens, allowing for flexible administration every 2, 3, or 4 weeks.

Tecentriq is a PD-(L)1 cancer immunotherapy that targets and binds to tumor cells andTumorIt blocks the interaction of PD-L1, a protein expressed on infiltrating immune cells, with the PD-1 and B7.1 receptors. By inhibiting PD-L1, Tecentriq activates T cells and holds the potential to serve as a foundational combination therapy for cancer immunotherapies, targeted therapies, and various cancer chemotherapy regimens.

To date, Tecentriq has been approved in the United States, the European Union, and other countries worldwide as a monotherapy, and in combination with targeted therapy and/or chemotherapy, for the treatment of various types of non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC), certain types of metastatic urothelial carcinoma (mUC), and PD-L1-positive metastatic triple-negativeBreast Cancer(mTNBC), hepatocellular carcinoma (HCC). In the United States, Tecentriq is also approved in combination with Cotellic (cobimetinib) and Zelboraf (vemurafenib) for the treatment of advanced BRAF V600 mutation-positiveMelanoma。

Roche has established a comprehensive development program for Tecentriq, encompassing multiple ongoing and planned Phase III studies across various cancer types, including lung, genitourinary, skin, breast, gastrointestinal, gynecologic, and head and neck cancers. This includes studies evaluating Tecentriq as monotherapy or in combination with other therapeutic agents. (Bioon.com)

Original Source: Pivotal Phase III Data at ASCO Show Genentech’s Tecentriq Helps Certain People With Early Lung Cancer Live Significantly Longer Without Their Disease Returning