21/02/2021
ახალგაზრდა ონკოლოგთა ჯგუფი აგრძელებს რუბრიკას, რომელიც შეეხება 2020 წლის სიახლეებს ონკოლოგიაში.
დღეს წარმოგიდგენთ ძუძუს კიბოს მართვის მნიშვნელოვან სიახლეებს. რუბრიკის ავტორია ამიკო მათითაშვილი, მარდალეიშვილის სამედიცინო ცენტრის კლინიკური ონკოლოგი.
10. Abemaciclib Shows 28.7% Reduction in Risk of Invasive Disease Recurrence or Death in HR+ Breast Cancer Subset
The phase 3 monarchE clinical trial (NCT03155997) demonstrated prolonged invasive disease-free survival (iDFS) with abemaciclib (Verzenio) in combination with standard endocrine therapy as treatment of patients with high-risk, early HR-positive, HER2-negative breast cancer.
Findings from SABCS showed a 28.7% reduction in the risk of invasive disease recurrence or death with the combination. The iDFS benefit was statistically significant and clinically meaningful after 395 events and a median follow-up of 19.0 months (HR, 0.713; 95% CI, 0.583-0.871; 2-sided P = .0009). The 2-year iDFS rate was 92.3% with the combination compared with 89.3% with endocrine therapy alone, which translated to a 3.0% difference.
9. Ribociclib Maintains Significant Survival Benefit in HR+/HER2– Breast Cancer
Treatment with ribociclib (Kisqali) and endocrine therapy improved overall survival (OS) and chemotherapy delay in patients with HR-positive, HER2-negative breast cancer, according to the findings from the phase 3 MONALEESA-7 clinical trial (NCT02278120).
The median OS was 58.7 months with the combination compared with 48.0 months with placebo plus endocrine therapy (HR, 0.763; 95% CI, 0.608-0.956), which translated to a 24% relative reduction in the risk of death with the addition of the CDK4/6 inhibitor to endocrine therapy. The findings observed in this study appeared consistent with those observed previously.
Moreover, these findings demonstrated a median OS of 58.7 months with the ribociclib regimen among patients who had received a nonsteroidal aromatase inhibitor compared with 47.7 months with placebo (HR, 0.798; 95% CI, 0.615-10.4), according to data from a subgroup analysis. These findings also demonstrated the median OS was not reached among patients who received tamoxifen compared with 49.3 months with placebo (HR, 0.705; 95% CI, 0.453-1.097).
8. Premenopausal Women With Lymph Node+, HR+, HER2- Breast Cancer Benefit From Chemotherapy Addition
The 5-year iDFS, as well as OS, were improved with the addition of chemotherapy to endocrine therapy in premenopausal but not postmenopausal women with HR-positive, HER2-negative, lymph node-positive breast cancer who had a recurrence score between 0 and 25, according to the prespecified interim analysis of the phase 3 RxPONDER study (NCT01272037).
Among the premenopausal population, the 5-year iDFS rate was 94.2% with the combination regimen versus 89.0% with endocrine therapy alone, reflecting an absolute difference of 5.2% (adjusted HR, 0.54; 95% CI, 0.38-0.76; P = .0004). In the postmenopausal patients, this rate was 91.6% with the combination versus 91.9% in the control arm (adjusted HR, 0.97; 95% CI, 0.78-1.22; P = .82).
7. Tesetaxel Plus Capecitabine Combo Improves PFS in HR+ Metastatic Breast Cancer
Treatment with the novel oral taxane tesetaxel in combination with a reduced dose of capecitabine (Xeloda) in patients with HER2-negative, HR-positive metastatic breast cancer resulted in an improvement compared with the FDA-approved dose of capecitabine alone in the phase 3 CONTESSA study (NCT04483557).
After a median follow-up of 13.9 months, the median progression-free survival (PFS) was 9.8 months with the combination compared with 6.9 months with capecitabine alone, which translated to a 2.9-month improvement (HR, 0.716; 95% CI, 0.573-0.895; P = .003). The safety profile appeared manageable that was consistent with what has been previously observed in clinical trials of the combination.
6. Clinical Benefit of Sacituzumab Govitecan in mTNBC Observed Irrespective of TROP-2 Expression
The ADC sacituzumab govitecan demonstrated clinical benefit compared with physician’s choice of therapy in patients with metastatic TNBC, irrespective of Trop-2 expression. Greater efficacy was observed among those with a medium or high Trop-2 score in the phase 3 ASCENT study (NCT02574455).The median PFS was higher in patients who received the ADC compared with those who were given physician’s choice, across all subgroups of Trop-2 analyzed. In the Trop-2 High subgroup, the median PFS was 6.9 months with the sacituzumab govitecan versus 2.5 months in the control arm, and in the Trop-2 medium subgroup, the median PFS was 5.6 months and 2.2 months, respectively, while the median in the Trop-2 low subset was 2.7 months versus 1.6 months.
5. Oral Paclitaxel Combination Reduces the Risk of Death in Patients With mBC
According to the findings from the phase 3 KK-ORAX-001 clinical trial, oral paclitaxel plus encequidar achieved a 26.5% reduction in the risk of death in patients with metastatic breast cancer compared with intravenous paclitaxel. The median OS in the modified intention-to-treat (mITT) population was 23.3 months with the combination versus 16.3 months in the control arm (HR, 0.735; 95% CI, 0.556-0.972; P = .0262).
In addition, these findings demonstrated the median PFS in the mITT population was 8.4 months with the combination versus 7.4 months with IV paclitaxel, which translated to a 26% reduction in the risk of disease progression or death (HR, 0.739; 95% CI, 0.561-0.974; P =.0223).
4. Trastuzumab Deruxtecan in DESTINY-Breast01 Demonstrates Continued Efficacy and Safety in HER2+ Metastatic Breast Cancer
The phase 2 DESTINY-Breast01 study (NCT03248492) demonstrated that patients with HER2-positive metastatic breast cancer who were treated with fam-trastuzumab deruxtecan-nxki (Enhertu) had continued to experience extended durable responses and OS rates, and the therapy appeared to have a tolerable toxicity profile.
With an additional 9.4 months of follow-up, investigators found the median duration of response was 20.8 months, and the 12- and 18-month OS rates were 85% (95%, 79%-90%) and 74% (95% CI, 67%-80%), respectively. Although data were still immature, the preliminary median OS was 24.6 months (95% CI, 23.1–NE). The median PFS was 19.4 months (95% CI, 14.1-not evaluable [NE]).
3. IMpassion031: Results from a phase III study of neoadjuvant (neoadj) atezolizumab + chemotherapy in early triple-negative breast cancer (TNBC)
333 pts were assigned to Atezolizumab-chemo (n = 165) or Placebo-chemo (n = 168). Median follow-up was 20.6 mos in the A-chemo arm and 19.8 mos in the P-chemo arm (data cutoff 3 Apr 2020). pCR was seen in 57.6% (95% CI: 49.7, 65.2) of pts in the A-chemo arm and 41.1% (33.6, 48.9) in the P-chemo arm (Δ16.5%; 5.9, 27.1; 1-sided P = 0.0044 [significance boundary, 0.0184], P = 0.0085 for the intersection hypothesis of ITT and PD-L1+ populations). In PD-L1+ pts (n=152), pCR was seen in 68.8% (57.3, 78.9) vs 49.3% (37.6, 61.1) of pts (Δ19.5%; 4.2, 34.8; 1-sided P = 0.021; not significant). Median EFS was not reached in either arm (HR, 0.76; 95% CI: 0.40, 1.44).
In pts with eTNBC, A + neoadj chemo significantly improved pCR rates regardless of PD-L1 status with an acceptable safety profile
2. Pembrolizumab plus chemotherapy versus placebo plus chemotherapy for previously untreated locally recurrent inoperable or metastatic triple-negative breast cancer (KEYNOTE-355): a randomised, placebo-controlled, double-blind, phase 3 clinical trial
Between Jan 9, 2017, and June 12, 2018, of 1372 patients screened, 847 were randomly assigned to treatment, with 566 patients in the pembrolizumab–chemotherapy group and 281 patients in the placebo–chemotherapy group. At the second interim analysis (data cutoff, Dec 11, 2019), median follow-up was 25·9 months (IQR 22·8–29·9) in the pembrolizumab–chemotherapy group and 26·3 months (22·7–29·7) in the placebo–chemotherapy group. Among patients with CPS of 10 or more, median progression-free survival was 9·7 months with pembrolizumab–chemotherapy and 5·6 months with placebo–chemotherapy (hazard ratio [HR] for progression or death, 0·65, 95% CI 0·49–0·86; one-sided p=0·0012 [primary objective met]). Median progression-free survival was 7·6 and 5·6 months (HR, 0·74, 0·61–0·90; one-sided p=0·0014 [not significant]) among patients with CPS of 1 or more and 7·5 and 5·6 months (HR, 0·82, 0·69–0·97 [not tested]) among the intention-to-treat population. The pembrolizumab treatment effect increased with PD-L1 enrichment.
1. Alpelisib plus Fulvestrant for HR+ HER2− Advanced Breast Cancer
In the prior phase III SOLAR-1 trial, adding the PIK3CA inhibitor alpelisib to fulvestrant significantly improved PFS in patients with PIK3CA-mutated HR+ HER2− breast cancer( N Engl J Med 2019; 380:1929). Now, Andre and colleagues report OS results from this trial (abstract LBA18).Median OS was nonsignificantly longer with alpelisib plus fulvestrant versus fulvestrant alone (39.3 and 31.4 months, respectively) in all patients as well as in those with more worrisome liver or lung metastases (37.2 and 22.8 months). Among patients for whom PIK3CA mutation was confirmed by circulating tumor DNA, the OS improvement with alpelisib was replicated. The time to chemotherapy was delayed by 8.5 months for those receiving alpelisib plus fulvestrant. No new toxicity concerns were identified.
The OS results and the delay to chemotherapy favor consideration of alpelisib in those with a PIK3CA mutation.
