Atezolizumab

Roche in consultation with the FDA has decided to withdraw the indication for atezolizumab in patients with urothelial carcinoma following platinum-based chemotherapy.

Also approved for cisplatinum ineligible patients with locally avanced or metastatic urothelial cancer.

In a study of 119 cisplatin ineligible, treatment naive patients with locally advanced metastatic urothelial cancer associated with a 23.5% response rate with 6.7% complete remission rate (IMvigor2 trial).

IMvigor 130 study randomized patients with metastatic urothelial tumors who were untreated and found that atezolizumab added to chemotherapy was associated with a significantly longer median disease free survival. (11.8 months vs. 6.3 months) than chemotherapy alone.

Patients with epidermal growth factor receptor (EGFR) were anaplastic lymphomaa kinase (ALK) to genomic tumor aberrations should have disease progression before receiving this drug.

Significantly improves overall survival compared to docetaxel in the second line stetting of advanced NSCLC.

Patients benefit regardless of magnitude of PD-L1 expression.

Its interaction is different from other PD-1 inhibitors as it inhibits B7-1 (CD80) priming the immune sysytem differently and acitivating the T cell differently.

Has activity in triple negative breast cancer.

FDA Approves Atezolizumab Combo for Frontline TNBC

Approval to the frontline combination of atezolizumab (Tecentriq) plus nab-paclitaxel (Abraxane) for patients with unresectable locally advanced or metastatic PD-L1–positive triple-negative breast cancer (TNBC).

The approval is based on the phase III IMpassion130 trial, in which the addition of the PD-L1 inhibitor atezolizumab to nab-paclitaxel reduced the risk of progression or death by 40% compared with nab-paclitaxel alone in this patient population.

Atezolizumab approved for use as an adjuvant treatment following resection and platinum-based chemotherapy in patients with stage II to IIIA non–small cell lung cancer whose tumors have PD-L1 expression on ≥ 1% of tumor cells, as determined by an FDA-approved test.

The phase 3 IMpower010 trial which showed that the median disease-free survival (DFS) was not yet reached in patients with stage IB through stage IIIA NSCLC who received treatment on the atezolizumab arm vs 35.3 months in those who were on the best supportive care.

In patients with stage II to IIIA NSCLC who had a PD-L1 tumor cell expression of 50% or higher, the hazard ratio for disease free survival was 0.43 . 

In patients who had a PD-L1 tumor cell expression ranging from 1% to 49%, the HR for DFS was 0.87.

It is now the first and only cancer immunotherapy available for adjuvant treatment of NSCLC, introducing a new era where people diagnosed with early lung cancer may have the opportunity to receive immunotherapy to increase their chances for cure.

IMpower010 enrolled patients with completely resected stage IB to IIIA NSCLC who had an ECOG performance status of 0 to 1, a lobectomy/pneumonectomy, and tumor tissue available for PD-L1 analysis.

A total of 1280 patients received cisplatin plus pemetrexed, gemcitabine, docetaxel, or vinorelbine for 1 to 4 cycles. 

Then, 1005 participants were randomized 1:1 to receive either atezolizumab at 1200 mg every 21 days for 16 cycles or best supportive care.

The median DFS with atezolizumab was 42.3 months vs 35.3 months with best supportive care.

The adverse effects that were most frequently reported in patients who received atezolizumab included increased aspartate aminotransferase, blood creatinine, and alanine aminotransferase, hyperkalemia, rash, cough, hypothyroidism, pyrexia, fatigue/asthenia, musculoskeletal pain, peripheral neuropathy, arthralgia, and pruritus.

The first cancer immunotherapy regimen to be approved in breast cancer,

The double-blind IMpassion130 study evaluated the efficacy and safety of the PD-L1 inhibitor plus chemotherapy versus nab-paclitaxel alone in treatment-naïve patients with metastatic TNBC.

Patients were randomized 1:1 to receive nab-paclitaxel at 100 mg/m2 intravenously on days 1, 8, and 15 of the 28-day cycle with atezolizumab at 840 mg intravenously (n = 451) on days 1 and 15 of a 28-day cycle or with placebo (n = 451):Treatment was given until disease progression or unacceptable toxicity.

PD-L1 expression, which was defined as at least 1% on tumor-infiltrating immune cells to be positive.

Progression free survival (PFS) of 7.4 months with atezolizumab/nab-paclitaxel and 4.8 months with chemotherapy.

Moreover, the 1-year PFS rates were 29% and 16% with atezolizumab/nab-paclitaxel and nab-paclitaxel, respectively.

The median PFS with atezolizumab/nab-paclitaxel and nab-paclitaxel was 7.2 months and 5.5 months respectively.

The1-year PFS rates were 24% in the combination arm and 18% in the nab-paclitaxel arm.

At a 12.9-month follow-up, an interim OS analysis of the PD-L1–positive population showed a clinically meaningful improvement with added atezolizumab at 25.0 months versus nab-paclitaxel alone at 15.5 months.

Two-year OS rates were 54% and 37% in the immunotherapy/chemotherapy and chemotherapy arms, respectively.

The FDA has granted an approval to the combination of atezolizumab (Tecentriq) with carboplatin and etoposide for the frontline treatment of patients with extensive-stage small cell lung cancer (ES-SCLC).

Phase III IMpower133 study, which demonstrated that the addition of atezolizumab to carboplatin and etoposide led to a significant improvement in overall survival (OS) in patients with ES-SCLC.

The median OS in IMpower133 was 12.3 months in the atezolizumab arm compared with 10.3 months in the carboplatin/etoposide and placebo arm, leading to a 30% reduction in the risk of death.

The median progression-free survival (PFS) was 5.2 months in the atezolizumab arm compared with 4.3 months in the placebo group.

There was no major difference in ORR between arms (60.2% vs 64.4%) or in median duration of response (4.2 vs 3.9 months).

Atezolizumab was associated with a higher 6-month PFS rate (30.9% vs. 22.4%), and a more than doubling 12-month PFS rate (12.6% vs 5.4%) compared with placebo.

It demonstrated superior 6-month (32.2% vs 17.1%) and 12-month (14.9% vs 6.2%) event-free rates.

In the Impower110 study it showed significantly prolonged overall survival compared with platinum-based chemotherapy in patients with newly diagnosed non-small cell lung cancer in tumors expressing high levels of PD-L1.