1. Randomized phase III trial of gemcitabine and cisplatin vs. gemcitabine alone inpatients with advanced non-small cell lung cancer and a performance status of 2:The CAPPA-2 study Lung Cancer. 2013 May 1. pii: S0169-5002(13)00155-4 R1 최윤영 / prof. 정재헌

2. Introduction  Platinum-based chemotherapy is the standard treatment for patients with advanced non-small cell lung cancer  The evidence of its efficacy among ECOG performance status (PS)2 patients is weak =>because these patients are excluded from clinical trials  No prospective randomized trial has tested the addition of cisplatin to single-agent chemotherapy in patients with advanced NSCLC and PS2.

3. Introduction  We started a randomized phase 3 trial (CAPPA-2, Cisplatin Added to Gemcitabine in Poor PerformanceAdvanced NSCLC patients – PS2) to assess whether the addition of cisplatin (60 mg/m2) to gemcitabine improved survival of PS2 patients with advanced NSCLC.

4. Patients  Patients with advanced NSCLC and ECOG PS2.  aged 18–70 years, cytologically or histologically confirmed NSCLC, stage IV or stage IIIB with malignant pleural effusion or metastatic supraclavicular nodes adequate organ function.  Exclude : symptomatic brain metas-tases, history of prior invasive malignancy or who had received previous chemotherapy

5. Methods (Study treatments) SingleCombination Gemcitabine : 1200 mg/m2 in 30 min i.v. on days 1 and 8 Gemcitabine : 1000 mg/m2 in 30 min i.v. on days 1 and 8 Cisplatin : 60 mg/m2 i.v. on days 1 Repeated every 3 weeks, for a maximum of 4 cycles, unless disease progression or unacceptable toxicity

6. Methods (Study treatments) On day 1 The minimum requirements to receive chemotherapy =>If these conditions were not met, chemotherapy was postponed. After a 3-week delay, if toxicity persisted, study protocol suggested to consider treatment interruption. Absolute neutrophil count (ANC) ≥1500/L, platelets ≥ 100,000/L, and no grade ≥ 2 non hematologic toxicity (Excluding alopecia). In case of febrile neutropenia, grade 3 or 4 thrombocytopenia or thrombocytopenia of any grade with bleeding or requiring transfusion, In case of grade 3 non-hematologic toxicity => 25% dose reduction Grade 4 non-hematologic toxicity=> 50% dose reduction or interruption

7. Methods (Study treatments)  On day 8 of each cycle, the minimum requirements to receive gemcitabine at full dose were : ANC ≥ 1500/ L, platelets ≥ 100,000/L, and the absence of non-hematologictoxicity (excluding alopecia and emesis).  In case of ANC ≥ 1000 and<1500/L, or in case of grade 1 non-hematologic toxicity => 25%dose reduction  Grade 2 non-hematologic toxicity => 50% dose reduction and omission.  If these conditions were not met, day 8 was omitted.

8. Methods (evaluation)  Before randomization : history and physical examination, blood count and biochemistry analyses, thoracic and abdominal CT or sono  Thereafter : blood counts were repeated weekly and biochemistry analyses were repeated at the end of each cycle.  Tumor response was assessed at the end of the second and fourth cycle of chemotherapy by using Response Evaluation Criteria In Solid Tumors (RECIST)

9. Methods(Sample size and statistical analysis)  Primary end-point : Overall survival (OS) * OS : the date of death, or the date of last follow up for alive patients.  Secondary endpoints : Progression-free survival (PFS), objective tumor response, toxicity, and health-related QoL were considered * PFS : PD, f/u loss without PD date of death for patients died without progression

10. Results From october 2008 to May 2012

11. Results 1. Median age : 63 years 2. Majority of patients : males (82%) stage IV disease (93%). 3. Histology : Non-squamous histology (52%) squamous histology one third 4. Prevalence of most common comorbidities was similar without COPD

12. Results Worsening condition

13. Results(OS) P value : 0.039 P value : 0.13 0.27

14. Results(PFS) P value : 0.017 P value : 0.31 0.06

15. Results

16. Conclusion  CAPPA-2 results show that the addition of cisplatin to single-agent gemcitabine improves survival as first-line treatment of PS2patients with advanced NSCLC.  The cisplatin-based regimen also significantly prolonged PFS