Goss 2009 INSTEP.
| Methods | Design: parallel‐group Randomisation: yes, method not stated Blinding: double‐blind, double‐dummy Withdrawals: stated |
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| Participants | Setting: multicentre study, hospital outpatient department Number eligible: 220 Number enrolled: 201 Number in treatment group: 100 Number in control group: 101 Number of withdrawals (treatment/control): 26/19 Number completing trial (treatment/control): 100/101 Age range: treatment 43 to 89, control 42 to 90 Sex: M 122, F 79 Ethnicity: white 193 NSCLC diagnosis: histologically or cytologically confirmed locally advanced or metastatic NSCLC not amenable to curative surgery or radiotherapy Inclusion criteria: age > 18 years, chemotherapy‐naive, WHO performance of 2 or 3, measurable disease (RECIST), no prior EGFR inhibitor therapy Exclusion criteria: untreated, newly diagnosed metastases in the CNS; other coexisting malignancies or malignancies diagnosed within the last 5 years other than basal cell carcinoma or cervical cancer in situ; fewer than 4 weeks since completion of wide‐field radiotherapy or persistence of any radiotherapy‐related toxicity; unresolved chronic toxicity greater than National Cancer Institute Common Toxicity Criteria for Adverse Events grade 2 from previous anticancer therapy (except alopecia); evidence of clinically active interstitial lung disease; prior treatment with epidermal growth factor receptor inhibitors, biologic or immunological therapy; and treatment with an investigational drug within the prior 30 days. Baseline characteristics of treatment/control groups: comparable |
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| Interventions | Gefitinib 250 mg/day plus best supportive care Placebo plus best supportive care |
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| Outcomes | Overall survival Progression‐free survival (PFS) Tumour response ‐ RECIST ASEs ‐ NCI‐CTC Haematology and biochemical parameters Quality of life Pulmonary symptom improvement (PSI) |
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| Notes | — | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Low risk | Quote: "randomly assigned 1:1 according to a randomisation scheme prepared by biostatics group, AstraZeneca" Comment: this was judged as a low risk of bias |
| Allocation concealment (selection bias) | Low risk | Central allocation Comment: this was judged as a low risk of bias |
| Blinding (performance bias and detection bias) All outcomes | Low risk | Quote: "double‐blind", "gefitinib and placebo tablets physically identical and presented in identical packaging" Comment: this was judged as a low risk of bias |
| Incomplete outcome data (attrition bias) All outcomes | Low risk | Attrition presented in Figure 1. Missing outcomes balanced in numbers across intervention groups with similar reasons for missing data across groups. Intention‐to‐treat analysis performed Comment: this was judged as a low risk of bias |
| Selective reporting (reporting bias) | Low risk | All prespecified outcomes were reported Comment: this was judged as a low risk of bias |
| Other bias | Unclear risk | Co‐authors are recipients of research grants and honoraria from industry Comment: this was judged as an unclear risk of bias |