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| Induction chemotherapy improving survival in locally advanced cervical cancer - Phase III GCIG INTERLACE trial results |
A recent phase III GCIG INTERLACE trial revealed that administering a short-course of induction chemotherapy before chemoradiotherapy significantly improves survival outcomes for patients with locally advanced cervical cancer. The trial’s findings suggest this approach should be considered in clinical guidelines for treating such cases.
Key Findings: Improved Progression-Free and Overall Survival Rates
The study was conducted with an intention-to-treat analysis, which highlighted that administering dose-dense carboplatin and paclitaxel once a week prior to standard chemoradiotherapy yielded an 11% increase in progression-free survival (PFS) and a 10% increase in overall survival (OS) rates after 5 years. These improvements were both clinically and statistically significant, demonstrating that induction chemotherapy plays a key role in enhancing treatment efficacy.
The combination of short-course induction chemotherapy followed by chemoradiotherapy reduced the risk of disease progression or death by 35% compared to chemoradiotherapy alone. Additionally, there was a 40% reduction in the risk of mortality for patients who received the induction chemotherapy regimen. The hazard ratio (HR) for PFS was 0.65, and for OS, it was 0.60, both indicating a substantial benefit. [Lancet 2024; doi:10.1016/S0140-6736(24)01438-7]
Long-Term Benefits
The trial results demonstrated that the 3-year PFS rate in patients receiving both induction chemotherapy and chemoradiotherapy was 75%, compared to 72% in the group treated with chemoradiotherapy alone. At the 5-year mark, PFS rates were 72% and 64%, respectively. This translates to an absolute risk difference of 10.8 percentage points in favor of the induction chemotherapy group.
Similarly, the 3-year OS rate for the induction chemotherapy group was 85%, versus 80% for the chemoradiotherapy-only group. At 5 years, the OS rates were 80% for the induction group and 72% for the chemoradiotherapy-alone group. This represents an absolute risk difference of 10.2 percentage points in favor of the combination therapy.
These outcomes mark the first significant overall survival improvement in over two decades for patients with locally advanced cervical cancer, previously achieved through concomitant cisplatin treatment.
Safety and Adverse Events
Although the study showed promising survival benefits, it also highlighted an increased incidence of adverse events (AEs) in patients receiving induction chemotherapy. Grade 3 or higher AEs occurred in 59% of patients receiving both induction chemotherapy and chemoradiotherapy, compared to 48% in the chemoradiotherapy-only group.
As expected, hematological toxicity, particularly neutropenia, was more prevalent in the induction chemotherapy group (19%) compared to the chemoradiotherapy-only group (5%). Despite this, the investigators reassured that the rates of thrombocytopenia were low, and no significant differences in vaginal symptoms or bleeding were reported between the two groups. Thus, the study suggests that vaginal bleeding should not be a contraindication for this treatment approach.
Notably, hair loss, peripheral neuropathy, fatigue, constipation, and dyspnoea were documented, but these were all transient side effects. No grade 3 thrombocytopenia was observed, and only 4% of patients experienced grade 1–2 thrombocytopenia.
GCIG INTERLACE Trial Design
The study involved 500 patients with a median age of 46 years, all diagnosed with locally advanced cervical cancer. Participants were randomly divided into two groups: one receiving standard cisplatin-based chemoradiotherapy alone, and the other receiving an additional short-course of induction chemotherapy with carboplatin and paclitaxel before chemoradiotherapy.
Seventy percent of the patients had stage IIB cervical cancer, and 43% had pelvic lymph node involvement. Most patients (92%) in the induction chemotherapy group received at least five cycles, and the median interval between induction chemotherapy and chemoradiotherapy was 7 days. During follow-up, 85% of patients in the induction group and 90% in the chemoradiotherapy-alone group completed at least four cycles of cisplatin.
Implications for Future Treatment
The GCIG INTERLACE trial findings strongly suggest that induction chemotherapy, as outlined in the protocol, should be considered an option for improving outcomes in patients with locally advanced cervical cancer. These results alleviate longstanding concerns about the potential delay in delivering definitive chemoradiotherapy and highlight the effectiveness of a platinum-dense chemotherapy regimen administered weekly.
Looking forward, the inclusion of induction chemotherapy in clinical guidelines could serve as a foundation for future trials exploring the integration of immunotherapy or other targeted drugs in the first-line treatment of locally advanced cervical cancer.
This trial provides compelling evidence that short-course induction chemotherapy significantly enhances survival outcomes in locally advanced cervical cancer when followed by standard chemoradiotherapy. The treatment not only improves PFS and OS but also offers a promising approach that could change the standard of care for these patients.
Source:
1.
Short-Course Induction Chemotherapy Boosts Survival in Locally Advanced Cervical Cancer: The GCIG INTERLACE Trial - The Lancet
2.
Neoadjuvant Chemotherapy in Locally Advanced Cervical Cancer: A Systematic Review - European Journal of Cancer
3.
Neoadjuvant Chemotherapy for Cervical Cancer: A Comprehensive Review - Cancers (Basel)