Rahim ağzı(serviks) kanserinde yeni tedavi seçenekleri var
Serviks kanseri kadınlarda sık görülen bir kanser ve büyük oranda HPV virüsünün cinsel yola bulaşmasında oluşur.
Aşılama programları ile hastalık büyük oranda engellenebilir.
Cerrahi aşamasını geçmiş serviks kanserinde indüksiyon kemoterapisi sonrası kemoradiyoterapi(sisplatin haftalık) standart tedavi olan radyoterapiye göre daha başarılı olduğu saptandı
Altı hafta boyunca uygulanan karboplatin ve paklitaksel tedavisi sonrası 5 hafta boyunca radyoterapi ve kemoterapi(sisplatin) kombinasyonuyla daha etkili sonuç alındı
Diğer önemli başarı, evre IV serviks kanserinde ikinci basamak tedavide daha etkili bir molekül artık mevcut
Tisotumab vedotin adlı molekül, serviks tümöründe bol sentezlenen tissue factor(TF) bağlanan antikor kısmı ve tümör içinde açığa çıkan kemoterapi (Monomethyl Auristatin)kısmından oluşuyor.
Tisotumab vedotin bu özeliği ile tümör içinde daha yüksek oranda sitotoksik kemoterapinin birikmesine neden oluyor ve böylece tümör hücrelerinin ölmesine neden oluyor.
Bu yeni ilaç standart kullanılan kemoterapi tedavisine göre daha etkili olduğu belirlendi.
Bu veriler ışığında, Amerika Birleşik Devletleri Gıda ve İlaç Dairesi (FDA), daha önce bir seri sistemik tedavi almış hastalarda Tisotumab vedotin bir tedavi seçeneği olarak onayladı.
Kaynak
ESMO 2023
Background
Locally advanced cervical cancer (LACC) is treated with chemoradiation (CRT). However, many patients relapse and die from metastatic disease. A feasibility study demonstrated a good response rate to short course weekly induction chemotherapy (IC) delivered before standard CRT and the INTERLACE trial investigated whether this approach improves both progression free survival (PFS) and overall survival (OS).
Methods
Women with squamous, adeno or adenosquamous carcinoma FIGO (2008) stage IB1 node positive,IB2,II,IIIB, IVA were eligible. Patients were randomised (1:1) to receive either CRT alone (5 cycles weekly cisplatin) or IC (6 weeks carboplatin AUC2 and paclitaxel 80mg/m2) followed by the same CRT in week 7. Mandated minimum total EQD2 dose 78Gy to Point A with 3D brachytherapy recommended. All centres underwent radiation quality assurance. Primary endpoints were PFS (target hazard ratio [HR] 0.65) and OS (target HR 0.65-0.70).
Results
500 patients were recruited from 32 centres in 5 countries (Nov 2012-Nov 2022). Median age 46 (range 24-78) years. Stage distribution was: IB1/2; 9%, II;77%, IIIB;11% and IVA;3%. 57% were node negative and 82% squamous subtype. Arms were balanced. 92% of IC patients had 5/6 cycles carboplatin/paclitaxel. Median interval from IC to CRT was 7 days. 84% (IC/CRT) vs. 89% (CRT alone) had 4/5 cycles cisplatin. In the CRT arm 92% and 89% completed external beam and brachytherapy respectively; corresponding figures in the IC/CRT arm were 97% and 95%. The median overall treatment time for CRT was 45 days in both arms. Grade ≥3 adverse events were seen in 59% (IC/CRT) vs. 48% (CRT alone). Median follow up 64 months. 5 year PFS rate is 73% with IC/CRT and 64% with CRT alone (HR 0.65; 95%CI:0.46-0.91, p=0.013). The corresponding 5-year OS rates are 80% and 72% (HR 0.61:95%CI:0.40-0.91, p=0.04).
Conclusions
Induction chemotherapy followed by CRT significantly improves PFS and OS in LACC and should be considered a new standard of care. INTERLACE recruited patients from diverse health care settings demonstrating that IC followed by CRT is feasible in all countries.
Clinical trial identification
EudraCT: 2011-001300-35.
Background
Tisotumab vedotin (TV) is an investigational antibody-drug conjugate composed of a tissue factor-directed human monoclonal antibody covalently linked to cytotoxic MMAE. In the US, TV monotherapy received accelerated approval for the treatment of adult pts with recurrent or metastatic cervical cancer (r/mCC) with disease progression on or after chemotherapy. Here, innovaTV 301 (NCT04697628) study results of TV vs investigator’s choice of chemotherapy in pts with r/mCC following 1L therapy are presented.
Methods
Eligible pts had r/mCC with disease progression on/after treatment with standard of care chemotherapy doublet ± bevacizumab ± anti-PD-(L)1 therapy, measurable disease per RECIST v1.1, and ECOG PS 0-1. Pts were randomized 1:1 to TV monotherapy or investigator’s choice of topotecan, vinorelbine, gemcitabine, irinotecan, or pemetrexed. The primary endpoint was OS. Key secondary endpoints included PFS and confirmed ORR by investigator.
Results
502 pts were randomized (TV: 253; chemotherapy: 249); median survival follow-up was 10.8 mo (95% CI, 10.3-11.6). Overall, median age was 50 yrs (range: 26-80); arms were balanced for demographics and disease characteristics. 63.9% and 27.5% of pts had prior bevacizumab and prior anti-PD-(L)1 therapy, respectively. The TV arm had a 30% reduction in risk of death vs chemotherapy (HR 0.70; 95% CI 0.54-0.89; P=0.0038), with significantly longer median OS (11.5 mo [95% CI 9.8-14.9] vs 9.5 mo [95% CI 7.9-10.7]). PFS was superior in the TV vs chemotherapy arm (HR: 0.67 [95% CI, 0.54-0.82]; P<0.0001). Confirmed ORR was 17.8% and 5.2% in the TV and chemotherapy arms, respectively (odds ratio: 4.0; 95% CI, 2.1-7.6; P<0.0001). Most pts experienced at least 1 treatment-related adverse event (TV: 87.6% [grade ≥3: 29.2%] vs chemotherapy: 85.4% [grade ≥3: 45.2%]). AEs were consistent with the known TV safety profile, including for ocular, peripheral neuropathy, and bleeding AEs.
Conclusions
In the phase 3 innovaTV 301 study, TV showed a statistically significant and clinically meaningful improvement in OS, PFS, and ORR vs chemotherapy, with a manageable and tolerable safety profile in pts with 2L/3L r/mCC.
Clinical trial identification
SGNTV-003; Amendment 3 (6 April 2022), NCT04697628.
