Locally advanced cervical cancer is a significant disease affecting young women, and the standard treatment options have not seen substantial improvements since 1999. The addition of cisplatin chemotherapy to radiation therapy became the standard of care, resulting in a 5-year survival rate of approximately 60% for patients with locally advanced disease. However, there is still a need for further advancements to enhance patient outcomes.
Dr. Sudah Amarnath discusses, the NRG-GY006 clinical trial aimed to improve the outcomes for patients with locally advanced cervical or vaginal cancer by incorporating the ribonucleotide reductase inhibitor, triapine, into the cisplatin-based chemoradiation (CRT) regimen. The primary objective of the study was to evaluate the improvement in overall survival, with secondary objectives focusing on progression-free survival and metabolic response measured by post-treatment PET CT. The trial also utilized intensity-modulated radiation therapy with knowledge-based treatment planning.
Cisplatin-based chemoradiation is the current standard of care for cervical cancer treatment. By adding chemotherapy agents like cisplatin to radiation therapy, the survival rates of patients with locally advanced cervical cancer improved significantly. Cisplatin acts as a radiation sensitizer, interrupting DNA repair processes and allowing radiation to effectively cause cell kill by preventing repair of radiation-induced DNA damage.
The rationale behind incorporating triapine, a ribonucleotide reductase inhibitor, into the CRT regimen was based on the promising results of phase 2 trials using hydroxyurea, a similar inhibitor. Triapine is a more potent inhibitor of ribonucleotide reductase than hydroxyurea, and its addition to the treatment regimen aimed to further enhance positive outcomes.
The NRG GY006 trial included 448 patients with locally advanced cervical or vaginal cancer. The median age of the patients was 47, ranging from 23 to 85 years old. The majority of patients had cervical cancer (93%), with squamous cell carcinoma accounting for 82% of cases. Stage 2 disease was present in 52% of patients, and the trial had a diverse patient population with representation from various ethnic backgrounds.
The patients were randomly assigned to either the standard of care arm (CRT alone) or the experimental arm (CRT + triapine). Both treatment groups received radiation therapy, with cisplatin administered in the standard care arm and cisplatin plus triapine in the experimental arm.
The primary endpoint of the NRG-GY006 trial was overall survival, with secondary endpoints including progression-free survival, metabolic response on 3-month PET CT, and knowledge-based planning with intensity-modulated radiation therapy. After a median follow-up of 28 months, the study results showed that triapine did not improve overall survival compared to the standard of care.
Surprisingly, the initial promising results from the phase 2 trial were not replicated in the phase 3 trial. The absence of significant differences in toxicity profiles between the two treatment groups was observed, with no major variation in grade 3 to 5 toxicity. However, the negative outcome of the trial indicates the need for further research and exploration of alternative treatment approaches.
Future studies are required to validate these findings and to discover novel strategies to improve the outcomes for patients with locally advanced cervical cancer. The negative results from recent trials highlight the challenges faced in finding effective treatments for this disease. Enrolling patients in phase 3 clinical trials remains crucial for advancing knowledge and providing better care in the long run.