The pivotal trials

IPASS

Study design

IPASS (IRESSA Pan‐ASia Study) was an open‐label, randomised, parallel‐group study that assessed the efficacy, safety and tolerability of IRESSA (gefitinib) versus platinum‐based doublet chemotherapy (carboplatin/paclitaxel) as first‐line treatment in a clinically selected population of patients from Asia with advanced non‐small cell lung cancer (NSCLC). The primary endpoint of IPASS was progression‐free survival (PFS – the length of time a patient lives without their tumour progressing), with the objective of demonstrating that IRESSA was non‐inferior to platinum‐based doublet chemotherapy (carboplatin/paclitaxel).1

The study enrolled a selected population of 1217 patients in Asia with advanced NSCLC who had not received prior chemotherapy for advanced disease, whose tumours were of adenocarcinoma histology and who had either never smoked, or were former light smokers (ceased smoking at least 15 years ago and ≤10 pack‐years of exposure). These were the patients who had shown the most benefit in the IRESSA Survival Evaluation in Lung Cancer (ISEL) trial.2

IPASS (IRESSA Pan-ASia Study) design
IPASS (IRESSA Pan-ASia Study) design

*Never smokers, <100 cigarettesin lifetime; light ex-smokers, stopped ≥15 years ago and smoked ≤10 pack years

†Limited to a maximum of six cycles; carboplatin/paclitaxel was offered to gefitinib patients at progression

‡EGFR mutations were detected with use of ARMS and the DxS EGFR29 mutation-detection kit

ARMS, Amplification Refractory Mutation System; EGFR, epidermal growth factor receptor

Mok TS et al. N Engl J Med 2009; 361: 947–957; Fukuoka M et al. J Clin Oncol 2011; 29: 2866-2874

Efficacy

For the first time a targeted monotherapy demonstrated significantly longer PFS than platinum‐based doublet chemotherapy (carboplatin/paclitaxel): IPASS (IRESSA Pan‐ASia Study) results demonstrated superior PFS compared with carboplatin/paclitaxel in the overall population of clinically selected patients from Asia with advanced non‐small cell lung cancer (NSCLC) (hazard ratio [HR] 0.74 [95% confidence interval (CI) 0.65, 0.85]; p<0.001).1

The epidermal growth factor receptor (EGFR) mutation status of a patient’s tumour was a strong predictor of benefit with IRESSA or carboplatin/paclitaxel. Pre‐planned subgroup analyses showed that PFS was significantly longer for IRESSA than carboplatin/paclitaxel in patients with EGFR mutation‐positive tumours (HR 0.48 [95% CI 0.36, 0.64]; p<0.001), and significantly longer for carboplatin/paclitaxel than IRESSA in patients with EGFR mutation‐negative tumours (HR 2.85 [95% CI 2.05, 3.98]; p<0.001).1

Kaplan-Meier curves of progression-free survival for (A) patients with EGFR mutation-positive and (B) EGFR mutation-negative advanced NSCLC from the IRESSA Pan-ASia Study (IPASS)
Kaplan-Meier curves of progression-free survival for (A) patients with EGFR mutation-positive and (B) EGFR mutation-negative advanced NSCLC from the IRESSA Pan-ASia Study (IPASS)

C/P, carboplatin/paclitaxel; EGFR, epidermal growth factor receptor; NSCLC, non-small cell lung cancer

From Mok TS et al. N Engl J Med 2009;361:947–957. Copyright© 2009. Massachusetts Medical Society. Reprinted with permission from Massachusetts Medical Society; Median PFS from Fukuoka M et al. J Clin Oncol 2011;29:2866–2874

In the overall population, the objective response rate (ORR) was significantly higher with IRESSA than with carboplatin/paclitaxel (43.0% versus 32.2%, odds ratio [OR] 1.59 [95% CI 1.25, 2.01]; p=0.0001). For patients with EGFR mutation‐positive tumours, ORR was 71.2% with IRESSA versus 47.3% with carboplatin/paclitaxel (OR 2.75 [95% CI 1.65, 4.60]; p=0.0001). For patients with EGFR mutation‐negative tumours, ORR was 1.1% (one patient) with IRESSA versus 23.5% with carboplatin/paclitaxel (OR 0.04 [95% CI 0.01, 0.27]; p=0.0013).1

Summary of efficacy endpoints from the IRESSA Pan-ASia Study (IPASS)
Summary of efficacy endpoints from the IRESSA Pan-ASia Study (IPASS)
NOTE: HR <1 implies a lower risk of progression or death on IRESSA; OR >1 implies a greater chance of response on IRESSA
CI, confidence interval; DCR, disease control rate (complete response [CR] + partial response [PR] + stable disease);
HR, hazard ratio; ITT, intent-to-treat; NR, not reported; ORR, objective response rate (CR + PR); OR, odds ratio; OS, overall survival; PFS, progression-free survival
Mok TS et al. N Engl J Med 2009; 361: 947–957; Fukuoka M et al. J Clin Oncol 2011; 29: 2866-2874

NOTE: HR <1 implies a lower risk of progression or death on IRESSA; OR >1 implies a greater chance of response on IRESSA

CI, confidence interval; DCR, disease control rate (complete response [CR] + partial response [PR] + stable disease); HR, hazard ratio; ITT, intent-to-treat; NR, not reported; ORR, objective response rate (CR + PR); OR, odds ratio; OS, overall survival; PFS, progression-free survival

Mok TS et al. N Engl J Med 2009; 361: 947–957; Fukuoka M et al. J Clin Oncol 2011; 29: 2866-2874

Treatment with IRESSA was also associated with a more favourable tolerability profile and better quality of life for patients versus carboplatin/paclitaxel. Significantly more patients recorded sustained clinically relevant improvements in health-related quality of life measures and symptoms with IRESSA versus carboplatin/paclitaxel in patients with EGFR mutation-positive tumours, and with carboplatin/paclitaxel versus IRESSA in patients with EGFR mutation‐negative tumours.2

IRESSA demonstrated clinically relevant improvements, with patients reporting significantly improved quality of life and lung-symptom control with IRESSA versus carboplatin/paclitaxel.1

Percentage of patients with EGFRm NSCLC, and clinically relevant improvements for ≥21 days
Percentage of patients with clinically relevant improvement

FACT-L, functional assessment of cancer therapy-lung; LCS, lung cancer subscale

Clinically relevant improvement predefined as ≥6-point improvement for FACT-L, ≥2-point improvement for LCS, maintained for at least 21 days from EMA.

Adapted from IRESSA EU Summary of Product Characteristics. Available at http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/001016/WC500036358.pdf. Accessed 03 July 2017.

PFS by subtype

IPASS demonstrated consistent PFS, regardless of mutation subtype (exon 19 deletions and exon 21 L858R mutations). PFS was significantly longer for IRESSA versus carboplatin/paclitaxel in both the exon 19 deletion (HR, 0.38; 95% CI, 0.26 to 0.56) and the L858R mutation (HR, 0.55; 95% CI, 0.35 to 0.87) subgroups.3

Kaplan-Meier curves of progression-free survival for (A) patients with EGFR mutation-positive and (B) EGFR mutation-negative advanced NSCLC from the IRESSA Pan-ASia Study (IPASS)
Kaplan-Meier curves of progression-free survival for (A) patients with EGFR mutation-positive and (B) EGFR mutation-negative advanced NSCLC from the IRESSA Pan-ASia Study (IPASS)

C/P, carboplatin/paclitaxel; EGFR, epidermal growth factor receptor

From Fukuoka M et al. J Clin Oncol 2011;29:2866–2874

Safety

The safety profile of IRESSA in IPASS (IRESSA Pan-ASia Study) was generally consistent with its prescribing information, previous IRESSA studies in the relapsed setting and underlying disease. The most commonly reported adverse events with IRESSA were mild to moderate rash and diarrhoea. Compared with platinum-based doublet chemotherapy, IRESSA is generally well tolerated, with the most common adverse events being mild to moderate skin rash and diarrhoea (Common Terminology Criteria for Adverse Events grade 1 or 2).1,4,5 It is not typically associated with the cytotoxic side-effects commonly seen with chemotherapy.6,7 For more detailed information about safety, please see the IRESSA EU Summary of Product Characteristics

Most common AEs (≥10% on either treatment) with at least 5% difference between the groups (all groups)
Most common AEs (All Grades)

*Grouped term(sum of several preferred terms)

†The laboratory values for absolute neutrophil count in the case of neutropenia, haemoglobin in the case of anaemia, and white-cell count in the case of leucopenia, worsened from baseline to CTC Grade 3/4; IRESSA, n=599, carboplatin/paclitaxel, n=577

From Mok TS et al. N Engl J Med 2009;361: 947–957

*Grouped term(sum of several preferred terms).

†The laboratory values for absolute neutrophil count in the case of neutropenia, haemoglobin in the case of anaemia, and white-cell count in the case of leucopenia, worsened from baseline to CTC Grade 3/4; IRESSA, n=599, carboplatin/paclitaxel, n=577

From Mok TS et al. N Engl J Med 2009;361: 947–957

Most common AEs (Grades 3-5)
Most common AEs (Grades 3-5)

*Grouped term(sum of several preferred terms)

†The laboratory values for absolute neutrophil count in the case of neutropenia, haemoglobin in the case of anaemia, and white-cell count in the case of leucopenia, worsened from baseline to CTC Grade 3/4; IRESSA, n=599, carboplatin/paclitaxel, n=577

From Mok TS et al. N Engl J Med 2009;361: 947–957

*Grouped term(sum of several preferred terms)

†The laboratory values for absolute neutrophil count in the case of neutropenia, haemoglobin in the case of anaemia, and white-cell count in the case of leucopenia, worsened from baseline to CTC Grade 3/4; IRESSA, n=599, carboplatin/paclitaxel, n=577

From Mok TS et al. N Engl J Med 2009;361: 947–957

References

  1. Mok TS et al. Gefitinib or carboplatin–paclitaxel in pulmonary adenocarcinoma. N Engl J Med 2009; 361: 947–957.
  2. Thongprasert S et al. Health-related quality-of-life in a randomized phase III first-line study of gefitinib versus carboplatin/paclitaxel in clinically selected patients from Asia with advanced NSCLC (IPASS). J Thorac Oncol 2011; 6: 1872−1880.
  3. Fukuoka M et al. Biomarker analyses and final overall survival results from a phase III, randomized, open-label, first-line study of gefitinib versus carboplatin/paclitaxel in clinically selected patients with advanced non-small-cell lung cancer in Asia (IPASS). J Clin Oncol 2011;29(21):2866-2874.
  4. Maemondo M et al. Gefitinib or chemotherapy for non-small-cell lung cancer with mutated EGFR. N Engl J Med 2010; 362: 2380–2388.
  5. Mitsudomi T et al. Gefitinib versus cisplatin plus docetaxel in patients with non-small-cell lung cancer harbouring mutations of the epidermal growth factor receptor (WJTOG3405): an open label, randomised phase 3 trial. Lancet Oncol 2010; 11: 121–128.
  6. Thatcher N et al. Gefitinib plus best supportive care in previously treated patients with refractory advanced non‐small‐cell lung cancer: results from a randomised, placebo‐controlled, multicentre study (Iressa Survival Evaluation in Lung Cancer). Lancet 2005; 366: 1527–1537.
  7. Forsythe B and Faulkner K. Overview of the tolerability of gefitinib (IRESSA) monotherapy: clinical experience in non-small-cell lung cancer. Drug Saf 2004; 27: 1081–1092.

IPASS BICR

IPASS by blinded independent central review

At the request of the US Food and Drug Agency (FDA), a post-hoc analysis of the IPASS progression-free survival (PFS) data according to blind independent central review (BICR) was performed.1

Study design

Computerised tomography (CT) scans from patients with epidermal growth factor receptor (EGFR) mutation-positive non-small cell lung cancer (NSCLC) who had enrolled in the IPASS study were retrospectively reviewed.1 Scans were reviewed by a third party using a double read with adjudication paradigm, with predefined assessment criteria for RECIST (Response Evaluation Criteria in Solid Tumors) progression.1 Reviewers were blinded to all investigational site scan results and patient treatment assignment, with the review performed independently.1

Results

A total of 261 patients in IPASS harboured EGFR mutation-positive tumours, of which CT scans from 186 were available for BICR. Patient demographics were consistent between the BICR population, the overall EGFR mutation-positive population, and the overall study population.1,2

Consistent with the PFS results from IPASS (IRESSA vs carboplatin/paclitaxel, median PFS: 9.5 vs 6.3 months; hazard ratio [HR] 0.48 [95% confidence interval (CI) 0.36, 0.64]; p<0.001),3,4 PFS according to BICR showed a statistically significant improvement with IRESSA vs carboplatin/paclitaxel in patients with EGFR mutation-positive tumours: median PFS 10.9 vs 7.4 months (HR 0.54 [95% CI 0.38 to 0.79], p=0.0012).1

Kaplan-Meier curves of progression-free survival for patients with EGFR mutation-positive advanced NSCLC from the IRESSA Pan-ASia Study (IPASS), as measured by BICR
PFS for EGFR_BICR

BICR, blinded independent review; C/P, carboplatin/paclitaxel; EGFR, epidermal growth factor receptor

From Mok TSK, Saijo N, Thongprasert S, et al. Poster presented at: 16th Annual International Lung Cancer Congress; July 30-August 1, 2015; Huntington Beach, CA

Objective response rate (ORR) by BICR (IRESSA [gefitinib] 67.1%, carboplatin/paclitaxel 40.8%) was consistent with that reported by investigator assessment (71.2% and 47.3%, respectively).1,3,4 Median duration of response by BICR was reported as 9.6 months for IRESSA-treated patients and 5.5 months for carboplatin/paclitaxel-treated patients.1

Objective response rate for patients with EGFR mutation-positive advanced NSCLC from the IRESSA Pan-ASia Study (IPASS), as measured by BICR
Objective response rate for patients with EGFR mutation-positive advanced NSCLC from the IRESSA Pan-ASia Study (IPASS), as measured by BICR

BICR, blinded independent review; EGFR, epidermal growth factor receptor; ORR, objective response rate

Mok TS et al. Annals of Oncology 2015;26(Suppl 9):ix125–ix147

Objective response rate for patients with EGFR exon 19 deletion and EGFR L858R mutation from the IRESSA Pan-Asia Study (IPASS), as measured by BICR

BICR, blinded independent review; EGFR, epidermal growth factor receptor; ORR, objective response rate

From AZ Data on File

Interpretation

The PFS analysis for the EGFR mutation-positive population by BICR (IRESSA vs carboplatin/paclitaxel, median PFS: 10.9 months vs 7.4 months) was consistent with the investigator-assessed analysis of PFS for the IPASS study (IRESSA vs carboplatin/paclitaxel, median PFS: 9.5 vs 6.3 months).1,2 This provides confidence in the robustness of the PFS benefit provided by IRESSA over carboplatin/paclitaxel, as the BICR analysis potentially limits bias included in the investigator-assessed analysis, and is recommended by the FDA in trials where blinding cannot be used or when there is uncertainty of the blinding.1,2,5

References

  1. Mok TS et al. Efficacy by blind independent central review (BICR): Post hoc analyses of the phase III, multicentre, randomised IPASS study of 1st-line gefitinib (G) vs carboplatin/paclitaxel (C/P) in Asian patients (pts) with EGFR mutation-positive advanced NSCLC. Annals of Oncology 2015;26 (Suppl 9): ix125–ix147.
  2. Mok TSK et al. Progression-free survival (PFS) according to blind independent central review (BICR): a post-hoc analysis from the phase III, multicenter, randomized IPASS study of first-line gefitinib versus carboplatin/paclitaxel in Asian patients with EGFR mutation-positive advanced non-small-cell lung cancer (aNSCLC). Poster presented at: 16th Annual nternational Lung Cancer Congress; July 30-August 1, 2015; Huntington Beach, CA.
  3. Mok TS et al. Gefitinib or carboplatin–paclitaxel in pulmonary adenocarcinoma. N Engl J Med 2009; 361: 947–957.
  4. Fukuoka M et al. Biomarker Analyses and Final Overall Survival Results From a Phase III, Randomized, Open-Label, First-Line Study of Gefitinib Versus Carboplatin/Paclitaxel in Clinically Selected Patients With Advanced Non–Small-Cell Lung Cancer in Asia (IPASS). J Clin Oncol 2011; 29: 2866-2874.
  5. Amit O et al. Blinded Independent Central Review of the Progression-Free Survival Endpoint. Oncologist 2010; 15: 492–495.

IFUM

The IFUM study

Rationale

In June 2009, the European Medicines Agency (EMA) approved IRESSA (gefitinib) for the treatment of adult patients with locally advanced or metastatic non‐small cell lung cancer (NSCLC) with activating mutations of epidermal growth factor receptor tyrosine kinase (EGFR‐TK).2 At the time of EU approval of IRESSA, the majority of first‐line EGFR mutation‐positive advanced NSCLC efficacy and safety data were from Asian populations (e.g. IPASS,3 NEJ0024 and WJTOG34055 studies) and there were limited data available on the efficacy and safety of IRESSA in Caucasian patients with EGFR mutation-positive advanced NSCLC. As part of the EU marketing authorisation approval process, AstraZeneca committed to conduct a follow‐up measure study of IRESSA in Caucasian patients with EGFR mutation-positive advanced NSCLC.1

Study design

The IFUM (IRESSA Follow‐Up Measure) study was a multicentre, single‐arm, open-label, Phase IV study of IRESSA as first‐line treatment in Caucasian patients (n=106) with activating, EGFR mutation-positive advanced NSCLC. IFUM was conducted in 13 countries across Europe.1

Patients with T790M, S768I and exon 20 insertion mutations, either alone or in combination with other mutations, were excluded from the study. The primary endpoint was objective response rate (ORR; by investigator assessment), and the objective response rate (ORR) was also analysed by a secondary, supportive, central review. No defined threshold on ORR was specified by the regulatory authorities.1

Secondary endpoints included disease control rate, progression‐free survival, overall survival, safety and tolerability, and correlation between clinical characteristics and tumour epidermal growth factor receptor (EGFR) mutation status. Comparison of EGFR mutation status between matched tumour and plasma (circulating tumour DNA; ctDNA) samples was a preplanned exploratory endpoint (results presented in the ctDNA testing section).1

IFUM (IRESSA Follow-Up Measure) study design
IFUM (IRESSA Follow-Up Measure) study design

*As detected using ARMS; ineligible mutations were exon 20 point mutations T790M or S768I, exon 20 insertions, either alone or in combination with activating, sensitising mutations

†Included patients who had received previous adjuvant chemotherapy or had completed prior surgery or radiotherapy >6 months prior to the start of study treatment and patients who had received palliative radiotherapy ≥4 weeks prior to the start of study treatment

‡Assessed 6-weekly by RECIST version 1.1

§Objective response rate was also analysed by a secondary, supportive, central review

ARMS, Amplification Refractory Mutation System; EGFR, epidermal growth factor receptor; NSCLC, non-small cell lung cancer; RECIST, Response Evaluation Criteria In Solid Tumors

Douillard J-Y et al. Br J Cancer 2014; 110: 55-62

Results

ORR by investigator assessment was 69.8% (95% confidence interval [CI] 60.5%, 77.7%) and median progression‐free survival (PFS) was 9.7 months (Figure A).1 These data are similar to those reported in the IPASS study.3,6 ORR by secondary, supportive, central review was 50.0% (95% CI 40.6%, 59.4%), and median overall survival was 19.2 months (Figure B).1

Kaplan-Meier curves for (A) progression-free survival and (B) overall survival (full analysis set population) from the IRESSA Follow-Up Measure (IFUM) study
Kaplan-Meier curves for (A) progression-free survival and (B) overall survival (full analysis set population) from the IRESSA Follow-Up Measure (IFUM) study

Reprinted by permission from Macmillan Publishers Ltd on behalf of Cancer Research UK; British Journal of Cancer, Douillard J-Y et al, 110: 55-62, copyright 2014

Safety

In the IFUM study, first‐line gefitinib was well tolerated, with adverse events (AEs) consistent with the characterised tolerability/safety profile for gefitinib and previous studies.1,3,6-9

The most commonly reported AEs (Common Terminology Criteria [CTC] any grade) with IRESSA were rash (44.9%), diarrhoea (30.8%), vomiting (13.1%), asthenia, cough and dry skin (all 11.2%), and nausea (10.3%).1 A total of 16 (15.0%) patients experienced AEs of CTC grade ≥3.1 Only two patients (1.9%) experienced a serious AE that was considered by the investigator to be related to treatment with gefitinib.1

For more detailed information about safety, please see the IRESSA EU Summary of Product Characteristics.

References

  1. Douillard J‐Y et al. First‐line gefitinib in Caucasian EGFR mutation‐positive NSCLC patients: a phase‐IV, open‐label, single‐arm study. Br J Cancer 2014; 110: 55–62.
  2. EMA. European Public Assessment Report Iressa Summary of Product Characteristics. 2009.
  3. Mok TS et al. Gefitinib or carboplatin−paclitaxel in pulmonary adenocarcinoma. N Engl J Med 2009; 361: 947–957.
  4. Maemondo M et al. Gefitinib or chemotherapy for non‐small‐cell lung cancer with mutated EGFR. N Engl J Med 2010; 362: 2380–2388.
  5. Mitsudomi T et al. Gefitinib versus cisplatin plus docetaxel in patients with non-small cell lung cancer harbouring mutations of the epidermal growth factor receptor (WJTOG3405): an open label, randomised phase 3 trial. Lancet Oncol 2010; 11: 121–128.
  6. IRESSA EU Summary of Product Characteristics. Available at http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/001016/WC500036358.pdf. Accessed 03 July 2017.
  7. Fukuoka M et al. Multi‐institutional randomized phase II trial of gefitinib for previously treated patients with advanced non‐small‐cell lung cancer. J Clin Oncol 2003; 21: 2237–2246.
  8. Kris MG et al. Efficacy of gefitinib, an inhibitor of the epidermal growth factor receptor tyrosine kinase, in symptomatic patients with non‐small cell lung cancer. A randomized trial. JAMA 2003; 290: 2149–2158.
  9. Kim ES et al. Gefitinib versus docetaxel in previously treated non‐small‐cell lung cancer (INTEREST): a randomised phase III trial. Lancet 2008; 372: 1809–1818.

NEJ002

The NEJ002 study

NEJ002 was an independently run prospective Phase III study in epidermal growth factor receptor mutation-positive patients in the first-line setting in Japan that compared IRESSA (gefitinib) with carboplatin/paclitaxel.1,2

The study demonstrated superior efficacy (progression-free survival [PFS] and objective response rate [ORR]), better tolerability and improvements in quality of life and lung cancer symptoms for significantly more EGFR mutation-positive patients treated with IRESSA than with carboplatin/paclitaxel.1,2

Median PFS was significantly longer with IRESSA than with carboplatin/paclitaxel (median 10.8 months vs 5.4 months; hazard ratio [HR] 0.30 [95% confidence interval (CI) 0.22, 0.41]; p<0.001).1,2 The ORR was also significantly higher with IRESSA (73.7% vs 30.7%, p<0.001).1 The median overall survival was 30.5 months in the IRESSA group and 23.6 months in the carboplatin/paclitaxel group (p=0.31).1

The most common adverse events (AEs) with IRESSA were rash, diarrhoea, and elevated levels of aspartate aminotransferase (AST) or alanine aminotransferase (ALT).1 The most common AEs with carboplatin/paclitaxel were appetite loss, neutropenia, anaemia, elevated levels of AST and ALT, and sensory neuropathy.1

References

  1. Maemondo M, et al. Gefitinib or chemotherapy for non-small-cell lung cancer with mutated EGFR. N Engl J Med 2010; 362: 2380–2388.
  2. Inoue A, et al. Updated overall survival results from a randomized phase III trial comparing gefitinib with carboplatin–paclitaxel for chemo-naïve non-small cell lung cancer with sensitive EGFR gene mutations (NEJ002). Ann Oncol 2013; 24: 54–59.

WJTOG3405

The WJTOG3405 Study

WJTOG3405 was a multicentre, open‐label, randomised, Phase III study of IRESSA (gefitinib) versus platinum‐based doublet chemotherapy (cisplatin/docetaxel) in Japanese patients with epidermal growth factor receptor mutation‐positive advanced NSCLC.1 The primary endpoint was progression-free survival (PFS) and secondary endpoints included overall survival (OS) and objective response rate (ORR).

PFS was significantly prolonged with IRESSA compared with cisplatin/docetaxel (median 9.2 vs 6.3 months; hazard ratio [HR] 0.489 [95% confidence interval (CI) 0.336, 0.710]; p<0.001).1 The ORR was significantly higher with IRESSA compared with cisplatin/docetaxel (62.1% vs 32.2%; p<0.0001) and OS was not significantly different between treatment arms.1

Haematological adverse events (AEs) were less frequent with IRESSA than with cisplatin/docetaxel.1 The most common AEs with IRESSA were rash, liver dysfunction, dry skin and diarrhoea, and with cisplatin/docetaxel the most common AEs were nausea, myelosuppression, fatigue and alopecia.1

References

  1. Mitsudomi T et al. Gefitinib versus cisplatin plus docetaxel in patients with non-small-cell lung cancer harbouring mutations of the epidermal growth factor receptor
    (WJTOG3405): an open label, randomised phase 3 trial. Lancet Oncol 2010; 11: 121–128.

ORR in pivotal studies

Objective tumor response rate in patients with EGFRm NSCLC in four pivotal studies

Consistent efficacy was demonstrated in the four robust studies, across patient demographics. An increased objective response rate was recorded in each study.1-4

Tumour Response Rate

Please note, this graph does not represent a comparison of trials

Adapted from Mok TS et al. N Engl J Med 2009;361:947–957; Mitsudomi T et al. Lancet Oncol 2010;11:121–128;

Maemondo M et al. N Engl J Med 2010;362:2380–2388; Douillard J-Y et al. Br J Cancer 2014;110:55–62

IPASS Study

Results from a Phase III, multicentre, open-label, randomised study of 1217 adult patients with previously untreated advanced pulmonary adenocarcinoma in East Asia. Patients were randomised to treatment with IRESSA (gefitinib) 250 mg/daily (n=609) or carboplatin and paclitaxel (dosage based on patient weight) (n=608) until disease progression, intolerable toxicity, a request by the patient or physician to discontinue treatment, serious noncompliance with the protocol, or completion of 6 chemotherapy cycles. The primary endpoint was progression-free survival (PFS); secondary endpoints included overall survival (OS), objective response rate (ORR), quality of life, reduction of symptoms, and safety.1

IFUM Study

Results from a Phase IV, multicentre, open-label, single-arm study of 107 Caucasian patients with previously untreated locally advanced or metastatic non-small cell lung cancer (NSCLC) and epidermal growth factor receptor (EGFR) mutations. Patients received IRESSA 250 mg until disease progression, intolerable toxicity, or patient request for discontinuation. The primary endpoint was ORR; secondary endpoints included PFS, disease control rate, OS, safety and tolerability, and correlation between clinical characteristics and baseline tumour EGFR mutation status.2

NEJ002 Study

Results from a Phase III, multicentre, open-label, randomised study of 230 Asian patients with previously untreated advanced or recurrent NSCLC and EGFR mutations. Patients were randomised to treatment with IRESSA 250 mg/day (n=114) or carboplatin/paclitaxel (dosage based on patient weight) (n=114) until disease progression, intolerable toxicity, or patient request for discontinuation. The primary endpoint was PFS; secondary endpoints included OS, ORR, and time to deterioration of performance status.3

WJTOG 3405 Study

Results from a Phase III, multicentre, open-label, randomised study of 177 Asian patients with previously untreated advanced or recurrent NSCLC and EGFR mutations. Patients were randomised to treatment with IRESSA 250 mg/day (n=88) or cisplatin 80 mg/m2 and docetaxel 60 mg/m2 (n=89) until disease progression, intolerable toxicity, or patient request for discontinuation. The primary endpoint was PFS; secondary endpoints included OS and ORR.4

References

  1. Mok TS, et al. Gefitinib or carboplatin-paclitaxel in pulmonary adenocarcinoma. N Engl J Med 2009; 361: 947-957.
  2. Douillard J-Y, et al First-line gefitinib in Caucasian EGFR mutation-positive NSCLC patients: a phase-IV, open-label, single-arm study. Br J Cancer 2014; 110: 55-62.
  3. Maemondo M, et al; the North-East Japan Study Group. Gefitinib or chemotherapy for non–small-cell lung cancer with mutated EGFR. N Engl J Med 2010; 362: 2380-2388.
  4. Mitsudomi T, et al; the West Japan Oncology Group. Gefitinib versus cisplatin plus docetaxel in patients with non-small-cell lung cancer harbouring mutations of the epidermal growth factor receptor (WJTOG3405): an open label, randomised phase 3 trial. Lancet Oncol. 2010; 11: 121-128.