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by Dr. C.H. Weaver M.D. updated 5/2019

Tarceva (erlotinib) is widely used in the management of EGFR + non-small cell lung cancer (NSCLC) and clinical studies suggests it improves survival in early stage disease, as part of initial treatment for stage IV NSCLC, as maintenance therapy and in select individuals with recurrent 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 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 Improves Disease-Free Survival in EGFR-Mutant, Early-Stage NSCLC

The precision cancer medicine Tarceva targeting EGFR improves survival in stage I-III NSCLC & appears better than chemotherapy!

The results of the phase 2 SELECT (Surgically Resected EGFR-Mutant Lung Cancer With Adjuvant Erlotinib Cancer Treatment) clinical trial evaluating the addition of Tarceva to adjuvant chemotherapy in patients with surgically treated EGFR positive NSCLC suggest an improvement in survival without cancer recurrence. (1)

Adjuvant chemotherapy improves the survival of patients with stage I-III NSCLC when compared to treatment with surgery alone and is now considered standard of care. (2,3,4) Efforts are ongoing to evaluate new precision cancer medicines to further improve the outcomes.

In the SELECT clinical trial 100 patients with stage IA to IIIA NSCLC were treated with oral Tarceva for up to 2 years following surgical removal of their cancer. The average 2-year survival without cancer recurrence was found to be 88% which is significantly higher compared with that observed historically which is ~ 76% for similar individuals treated with adjuvant chemotherapy alone.

The authors also reported that patients who developed recurrent disease typically still responded to retreatment with Tarceva and these individuals had not developed. an EGFR T790M acquired-resistance mutation.

While Tarceva appears to prolong survival and delay recurrence in this setting, it remains unclear if it actually cures more people or simply further delays recurrence. Comparative studies will need to be performed to determine if Tarceva is best used as part of initial therapy or could be used at the time of cancer recurrence. Early stage NSCLC patients who are EFGR positive should discuss the potential role of adjuvant TKI therapy with their doctor and consider participation in trials designed to determine their optimal use.

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.(5)

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%).
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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.(6)

​Tarceva Approved for Treatment of Recurrent NSCLC

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.(7)

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.(8)

  • 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.”

Can Tarceva be Combined With Other Treatments to Further Improve Outcomes?

When Tarceva is combined with Avastin (bevacizumab ) Cyramza, or Celebrex the combinations modestly delay cancer progression and prolong survival. Sutent has been combined with Tarceva without benefit.(10,11,12,15)

Avastin - Interim results of a phase 3 study show that combining Avastin with Tarceva improve progression-free survival (PFS) over Tarceva alone in patients with EGFR-positive NSCLC. A total of 228 patients with stage IIIB to IV or recurrent EGFR-positive NSCLC were treated with Tarceva with or without Avastin and directly compared. The interim analysis published in May 2019 reported that, the median PFS was 16.9 months for the combination compared to 13.3 months for Tarceva alone.(11)

Future studies with longer follow-up, and overall survival and quality-of-life data will be required to further assess whether the addition of Avastin is beneficial.

In another 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.

Targeted treatment combination consisting of Avastin or Cyramza and Tarceva may provide an effective alternative in some patients. Further study is necessary to determine which patients achieve the greatest benefit from each treatment combination. Patients should discuss treatment options with their physician regarding their individual risks and benefits of treatment.(13,14)


  1. Pennell NA, Neal JW, Chaft JE, et al. SELECT: a phase II trial of adjuvant erlotinib in patients with resected epidermal growth factor receptor-mutant non-small-cell lung cancer.J Clin Oncol. 2019;37(2):97-104. doi: 10.1200/JCO.18.00131
  2. The International Adjuvant Lung Trial Collaborative Group. Cisplatin-based adjuvant chemotherapy in patients with completely resected Non-Small Cell Lung Cancer. New England Journal of Medicine. 2004;350:351-360.
  3. Kato H, Ichinose Y, Ohta M, et al. A randomized trial of adjuvant chemotherapy with uracil-tegafur for adenocarcinoma of the lung. New England Journal of Medicine. 2004;350(17):1713-21.
  4. Strauss GM, Herndon J, Maddaus MA, et al. Randomized clinical trial of adjuvant chemotherapy with paclitaxel and carboplatin following resection in Stage IB non-small cell lung cancer: Report of Cancer and Leukemia Group B (CALGB) Protocol 9633. Journal of Clinical Oncology. 2004;22:Suppl 14S: Abstract #7019.
  5. 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.
  6. OSI Pharmaceuticals. FDA Approves Tarceva as a Maintenance Therapy for Advanced Non-small Cell Lung Cancer. Available at: . Accessed April 19, 2010.
  7. 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.
  8. 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.
  9. Pfizer news release. Topline Results From Phase 3 Trial of Sunitinib With Erlotinib in Advanced Non-Small Cell Lung Cancer (NSCLC). August 23, 2010.
  10. 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.
  11. *Lancet Oncol***. 2019 Apr 8. Epub ahead of print
  12. Pfizer news release. Topline Results From Phase 3 Trial of Sunitinib With Erlotinib in Advanced Non-Small Cell Lung Cancer (NSCLC). August 23, 2010.
  13. 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.
  14. Herbst R, Johnson D, Mininberg E, et al. Phase I/II Trial Evaluating the Anti-Vascular Endothelial Growth Factor Monoclonal Antibody Bevacizumab in Combination With the HER-1/Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor Erlotinib for Patients With Recurrent Non–Small-Cell Lung Cancer. Journal of Clinical Oncology. 2005;23:2544-2555.
  15. Reckamp K et al. A Phase I Trial to Determine the Optimal Biologic Dose of Celecoxib When Combined with Erlotinib in Advanced Non-Small Cell Lung Cancer. Clinical Cancer Research. 2006;12: 3381-338.

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