by Dr. C.H. Weaver M.D. updated 1/2019
Tarceva is currently approved for the treatment of advanced NSCLC after initial treatment has failed, or as maintenance therapy after chemotherapy.
These drugs are also being evaluated in the initial treatment of advanced NSCLC, and studies in newly diagnosed patients have suggested that cancers that contain a mutation in the EGFR gene are more likely to respond to Tarceva and Iressa. Among people with NSCLC, EGFR mutations are most common in people of Asian ethnicity, women, never-smokers, and those with a type of lung cancer known as adenocarcinoma.
Tarceva™ (erlotinib) improves survival as a single agent in patients with recurrent non-small cell lung cancer.
Lung cancer remains the leading cause of cancer deaths annually in the United States. Non-small cell lung cancer (NSCLC) refers to the type of cell within the lung from which the cancer originated and comprises approximately 75%-80% of all lung cancers. Once patients have recurred following chemotherapy, they are referred to as having recurrent NSCLC. Currently, treatment options are limited for patients with recurrent NSCLC and researchers continue to evaluate novel agents in the treatment of this disease.
The epidermal growth factor receptor (EGFR) pathway is a complex biological pathway that is involved in the stimulation and growth of cells. In many cancer cells, the EGFR is often over expressed and/or has a mutation within the pathway. Researchers continue to evaluate the role and complexity of EGFR and cancer, as well as newer agents and combinations of agents that may target the EGFR pathway to control cancer growth. Tarceva™ is an agent that targets the EGFR pathway. Tarceva™ binds to the inner part of the EGFR, inhibiting stimulation of the pathway. Other EGFR inhibitors, Erbitux® and Iressa®, have been approved by the FDA but Tarceva™ is unique from compared to other EGFR inhibitors in that it binds to the inside of the EGF receptor, instead of the outside portion like Erbitux® and Iressa®.
What Do The Studies Show?
Tarceva Outperforms Chemotherapy for Initial Treatment of Lung Cancer with an EGFR Mutation.
Among patients with advanced non-small cell lung cancer that tests positive for a mutation in the EGFR gene, initial treatment with the targeted therapy Tarceva® (erlotinib) produces better outcomes and fewer serious side effects than chemotherapy. These results were published in Lancet Oncology.(4)
To compare Tarceva with chemotherapy for the initial treatment of advanced NSCLC that tests positive for an EGFR mutation, researchers in China conducted a study among 165 patients with Stage IIIB or Stage IV NSCLC. Half the patients were treated with Tarceva and half were treated with combination chemotherapy consisting of Gemzar® (gemcitabine) and carboplatin.
- Treatment with Tarceva substantially delayed cancer progression. Median survival without cancer progression was 13.1 months among patients treated with Tarceva and 4.6 months among patients treated with chemotherapy.
- Serious side effects were also less common in the Tarceva group.
These results suggest that for patients with advanced NSCLC that tests positive for an EGFR mutation, initial treatment with Tarceva is more effective and better tolerated than chemotherapy. Tarceva has not yet been approved by the U.S. Food and Drug Administration for this purpose, but patients with newly diagnosed NSCLC may wish to talk with their doctor about whether EGFR testing may be appropriate. Testing for EGFR mutations may not be recommended for all patients with NSCLC. Some groups of patients—such as those with squamous cell NSCLC—are less likely than others to have an EGFR mutation.
Tarceva Maintenance Therapy
Tarceva maintenance therapy was evaluated in a Phase III clinical trial known as SATURN. Maintenance therapy refers to treatment that is given after initial treatment but before cancer progression.
The study enrolled more than 880 patients with advanced NSCLC that had not progressed following initial, platinum-based chemotherapy. Half the patients received Tarceva maintenance therapy, and half received a placebo.
- Compared with a placebo, overall survival was 23% better among patients treated with Tarceva, and progression-free survival was 41% better.
- The most common side effects among patients treated with Tarceva were rash (49%) and diarrhea (20%).
Based on these results, the FDA expanded the approval of Tarceva to include maintenance therapy in patients with locally advanced or metastatic non-small cell lung cancer that has not progressed after four cycles of platinum-based first-line chemotherapy.(2)
The pivotal multi-institutional clinical trial that led to Tarceva's™ approval in the treatment of recurrent NSCLC icluded 731 patients that had received prior chemotherapy. Half of the patients had been treated with 2 or more prior chemotherapy regimens. Patients in this trial were treated with either Tarceva™ alone or placebo (inactive substitute) and were directly compared. The overall anti-cancer response rate was 9% for patients treated with Tarceva™ and the average duration of response was nearly 8 months. Disease stabilization was achieved in 35% of patients treated with Tarceva™ and progression of cancer occurred in 38% of patients treated with Tarceva™. Conversely, 57% of patients who received placebo had disease progression. The average duration of overall survival was 6.7 months for patients treated with Tarceva™, compared with 4.7 months for those who received placebo. At one year, overall survival was approximately 31% for patients treated with Tarceva™, compared to 21% for those treated with placebo. Upon analysis of subgroups of patients and their respective outcomes to treatment, researchers noted that patients of female gender, those with a type of NSCLC called adenocarcinoma, and those who had never smoked had higher responses to Tarceva™. Patients who had never smoked also had a significantly improved survival while on Tarceva™ compared to those who smoked. Tarceva™ was very well tolerated, with rash and diarrhea being the most common side effects, the majority of which was mild to moderate in severity.
The researchers concluded that Tarceva™ as a single agent improved survival and was reasonably well tolerated in patients with recurrent NSCLC. Several clinical trials are continuing to evaluate Tarceva™ in lung cancer, either in different stages of the disease or in combination with other agents.
Tarceva® Has Significant Activity as Initial Treatment for Elderly Patients with NSCLC
According to results recently published in the Journal of Clinical Oncology, treatment with the single agent Tarceva® (erlotinib) is active and well tolerated when used as initial therapy for patients 70 years of age or older with advanced non–small cell lung cancer who have not received prior chemotherapy.
Elderly patients often cannot tolerate standard treatment including chemotherapy and radiation therapy, particularly if they have other existing medical conditions. Furthermore, patients may not wish to receive additional chemotherapy or radiation therapy if they have already undergone treatment with these modalities and have experienced a cancer recurrence.
Researchers from the Dana-Farber Cancer Center conducted a clinical trial to further evaluate Tarceva in the treatment of elderly patients with advanced NSCLC. This trial included 80 patients with a median age of 75 years. Forty percent of patients had received prior surgery and/or radiation therapy; however, no patients had received prior chemotherapy.(3)
- Partial regression of cancer (partial response) occurred in 10% of patients.
- 41% of patients had a stabilization of their disease for at least two months.
- The median survival time was nearly 11 months.
- At one year nearly half (46%) of patients were still alive.
- At two years nearly 20% of patients were still alive.
- All patients with EGFR mutations achieved a partial response or disease stabilization and had improved survival over patients without EGFR mutations.
The researchers concluded that treatment with Tarceva appears to be an effective treatment choice for some patients with NSCLC, particularly those with EGFR mutations. Further research is needed to clearly identify which patients will gain optimal benefit from Tarceva. The researchers stated, “Erlotinib merits consideration for further investigation as a first-line therapeutic option in elderly patients.”
Tarceva® Improves Survival in Recurrent Non-Small Cell Lung Cancer
According to a recent article published in the New England Journal of Medicine, the targeted agent Tarceva® (erlotinib) improves survival in patients with recurrent non-small cell lung cancer.
Lung cancer remains the leading cause of cancer deaths annually in the United States. Non-small cell lung cancer (NSCLC) refers to the type of cell within the lung from which the cancer originated. It comprises approximately 75 percent to 80 percent of all lung cancers. Once NSCLC has recurred following chemotherapy, it is referred to as recurrent NSCLC. Treatment options are currently limited for patients with recurrent NSCLC, however researchers continue to evaluate novel agents in the treatment of this disease.
The epidermal growth factor receptor (EGFR) pathway is a complex biological pathway that is involved in the stimulation and growth of cells. In many cancer cells, the EGFR is often overexpressed and/or has a mutation within the pathway. Researchers continue to evaluate the role and complexity of EGFR and cancer, as well as newer agents and combinations of agents that may target the EGFR pathway to control cancer growth. Tarceva is a targeted agent that is approved for the treatment of advanced, recurrent NSCLC and targets the EGFR pathway. Tarceva binds to the inner part of the EGFR, inhibiting stimulation of the pathway. Researchers speculate that Tarceva may play an important role in the treatment of some cancers, as two other EGFR inhibitors, Erbitux® and Iressa®, have recently been approved by the FDA for specific types of cancer. However, Tarceva differs from other approved EGFR inhibitors in that it binds to the inside of the EGF receptor, whereas Erbitux® and Iressa® bind to the outer portion. Researchers are also evaluating Tarceva in combination with other agents that inhibit the EGFR through different mechanisms.
Researchers from Canada recently conducted a clinical trial evaluating Tarceva in the treatment of recurrent NSCLC. This trial included 731 patients who had received at least one prior chemotherapy regimen, and approximately half of these patients had received at least two prior regimens. Participants were treated either with Tarceva or placebo (inactive substitute). Overall anti-cancer response rates were approximately 9 percent in patients treated with Tarceva, compared to less than one percent in patients who received placebo. The average duration of anti-cancer responses more than doubled for patients treated with Tarceva (eight months versus 3.7 months for those who received placebo). The average duration of survival with Tarceva was longer as well at 6.7 months for patients treated with Tarceva, compared to only 4.7 months for those who received placebo. Patients who were treated with Tarceva also had greater improvements in cough, pain and difficulty in breathing than those who received placebo.
The researchers concluded that Tarceva improves overall survival and quality of life in patients with recurrent NSCLC. Tarceva continues to be studied in clinical trials in an attempt to evaluate which patient or disease characteristics are associated with the greatest responses to the agent. Patients with recurrent NSCLC may wish to speak with their physician regarding their individual risks and benefits of treatment with Tarceva.
Can Tarceva be Combined With Other Treatments to Further Improve Outcomes?
Sutent - Reference: no
 Pfizer news release. Topline Results From Phase 3 Trial of Sunitinib With Erlotinib in Advanced Non-Small Cell Lung Cancer (NSCLC). August 23, 2010.
Avastin - In one trial of 120 patients with recurrent NSCLC treated with Avastin plus Tarceva experienced a trend toward improved progression-free survival in the groups treated with Avastin: 4.8 months for patients treated with chemotherapy/Avastin; 4.4 months for patients treated with Avastin/Tarceva; and 3.0 months for patients treated with chemotherapy only.
The researchers concluded that the targeted treatment combination consisting of Avastin and Tarceva may provide an effective alternative to chemotherapy in the treatment of relapsed NSCLC. Further study is necessary to determine which patients achieve the greatest benefit from each treatment combination. Patients with relapsed NSCLC may wish to speak with their physician regarding their individual risks and benefits of treatment including Avastin/Tarceva.
Reference: Fehrenbacher L, O’Neill V, Belani CP, et al. A phase II, multicenter, randomized clinical trial to evaluate the efficacy and safety of bevacizumab in combination with either chemotherapy (docetaxel or pemetrexed) or erlotinib hydrochloride compared with chemotherapy alone for treatment of recurrent or refractory non-small-cell lung cancer. Proceedings of the 42nd annual meeting of the American Society of Clinical Oncology. Atlanta, GA. June 2-6, 2006. Abstract # 7062.
Reference: Shepherd F, Pereira J, Ciuleanu T, et al. Erlotinib in Previously Treated Non–Small-Cell Lung Cancer. The New England Journal of Medicine. 2005; 353:123-132.
- ShepherdF, Pereira J, Ciuleanu T, et al. A randomized placebo-controlled trial of erlotinib in patients with advanced non-small cell lung cancer (NSCLC) following failure of 1st or 2nd line chemotherapy. A National Cancer Institute of Canada Clinical Trials Group (NCIC CTG) trial. Proceedings from the 40th annual meeting of the American Society of Clinical Oncology. June 2004. Abstract #7022.
- OSI Pharmaceuticals. FDA Approves Tarceva as a Maintenance Therapy for Advanced Non-small Cell Lung Cancer. Available at: . Accessed April 19, 2010.
- Jackman DM, Yeap BY, Lindeman NI, et al. Phase II clinical trial of chemotherapy-naïve patients >70 years of age treated with erlotinib for advanced non-small-cell lung cancer. Journal of Clinical Oncology. 2007;25:760-766.
- Zhou C, Wu Y-L, Chen G et al. Erlotinib versus chemotherapy as first-line treatment for patients with advanced EGFR mutation-positive non-small-cell lung cancer (OPTIMAL, CTONG-0802): A multicentre, open-label, randomized, phase 3 study. Lancet Oncology. Early online publication July 22, 2011.
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