INTERLACE STUDY IN CERVIX CANCER ANALYSIS

INTERLACE STUDY IN CERVIX CANCER ANALYSIS

1. SBRT LUNG Dr Kanhu Charan Patro MD,DNB(Radiation Oncology),MBA,FICRO,FAROI(USA),PDCR,CEPC Clinical Director, HOD (Radiation Oncology) ISRo - I nstitute of S tereotactic R adiation o ncology Mahatma Gandhi Cancer Hospital & Research Institute, Visakhapatnam [email protected] /M- [phone]/ www.drkanhupatro.com Let’s analyze INTERLACE

2. INTERLACE Trial Induction Chemotherapy followed by Chemoradiotherapy vs Chemoradiotherapy Alone

3. INTRODUCTION The INTERLACE trial investigates the effect of adding induction chemotherapy to standard chemo-radiotherapy in locally advanced cervical cancer to improve progression-free and overall survival. Trial conducted at 32 medical centers globally, including Brazil, India, Italy, Mexico, and the UK.

4. Which journal? Lancet Oncology

5. Who is the author? Multicentric

6. Which group? INTERLACE GROUP

7. Where? Multicentric

8. TYPE OF STUDY? Multicentric

9. TYPE OF STUDY?

10. What is the basis of the study? Metaanalysis/CXII study

11. Ethics adherence?

12. Funding?

13. Trial design

14. Inclusion and exclusion

15. Randomization

16. Trial profile ITT

17. TREATMENT DETAILS

18. Study Design and Participants Study Population: Stage IB1 with nodal involvement to Stage IVA cervical cancer (FIGO 2008 staging) Randomized Phase 3 trial with 500 patients Treatment arms: Induction chemotherapy (Carboplatin + Paclitaxel for 6 weeks) followed by chemoradiotherapy ( cisplatin -based) Chemoradiotherapy alone ( cisplatin -based)

19. Radiotherapy details

20. Follow up

21. End points

22. PRIMARY END POINTS Progression-Free Survival (PFS): Time from randomization to progression or death. Overall Survival (OS): Time from randomization to death from any cause.

23. SECONDARY END POINTS Adverse events (Grade 3–4 toxicity) Patterns of relapse (local vs distant metastasis) Quality of Life ( QoL ) assessed with EORTC QLQ-C30 and CX24 modules

24. Statistical analysis

25. Statistical analysis

26. Analysis

27. Study period

28. Demographic analysis

29. Demographic analysis

30. Adherence to chemotherapy

31. Adherence to radiotherapy

32. Adherence to radiotherapy

33. CENTRAL REVIEW

34. MEDIAN FOLLOW UP

35. KEY RESULTS 5-year PFS: 72% (NACT + CTRT) vs 64% (CTRT alone) 5-year OS: 80% (NACT + CTRT) vs 72% (CTRT alone) Distant metastasis: 7% (NACT + CTRT) vs 12% (CTRT alone) Grade 3–4 toxicity: 59% (NACT + CTRT) vs 48% (CTRT alone)

36. Kaplan–Meier PFS analysis

37. Kaplan–Meier OS analysis

38. Distance recurrence

39. Pa nodal recurrence

40. Adverse event analysis

41. TOXICITY Higher hematological toxicity in NACT arm (30% Grade 3–4 vs 13% in CTRT arm) Main toxicities: Neutropenia (19% vs 5%), Anemia (28% vs 17%) Non-hematological toxicities were similar between both groups

42. DEATH There were 3 deaths within 30 days of completing treatment, one (respiratory failure) in the induction chemotherapy with chemoradiotherapy group, and 2 in the chemoradiotherapy alone group (sepsis and pulmonary embolism); none were considered treatment-related.

43. QOL Temporary decline in QoL during induction chemotherapy phase No long-term differences between the two groups after treatment

44. What are the criticisms?

45. What are the criticisms?

46. Strong Points favoring the study This is a phase 3 study Electronic randomization of 500 patients. It was a Multicentric study involving around 32 nations. ITT analysis Significance level at 0.05 Power is level at 80% Central review of radiation details

47. Negative Points of the study FIGO 2008 staging was used to stage the patient prior to allocating the treatment arm. Acute toxicity was higher in the NACT arm Adherence to concurrent chemotherapy during radiotherapy was hindered in the NACT arm, resulting in deviation from the standard of care treatment. The increase in overall treatment time in the NACT arm is a concern. Temporary decline in the QOL is present in the NACT arm. 10 percent lost to follow up

48. Is it practice changing?

49. SUMMARY NACT followed by CTRT showed improved progression-free and overall survival compared to CTRT alone. Increased toxicity in the NACT arm but manageable with standard care. NACT + CTRT can be considered as a new standard of care for locally advanced cervical cancer.