To Bev or Not to Bev during Ovarian Cancer Maintenance Therapy?
Abstract
:Simple Summary
Abstract
1. Introduction
- Quality Assessment: The guideline should provide comprehensive details on the assessment of study quality and risk of bias for the included studies. This should encompass the tools or criteria used for evaluation;
- Evidence Synthesis: The guideline should clearly outline the methods employed to synthesize the evidence gathered from relevant studies; and
- Recommendations Formulation: The guideline should provide a clear description of the process used to formulate recommendations. This should include how the evidence was graded and how the values and preferences of the target population were taken into account.
2. Statistical Background
3. Questions
3.1. Q1: Is It Acceptable That Bevacizumab and PARPi Cannot Be Administered Again after Previous Treatment with the Same Medication?
3.2. Q2: In Which Treatment Line Is Bevacizumab More Efficacious—First or Second?
3.3. Q3: In Which Treatment Line Is PARPi More Efficacious—First or Second?
3.4. Q4: Can PARP Inhibitors Be Considered More Effective Than Bevacizumab in the First Line Treatment of Ovarian Cancer?
3.5. Q5: Can Combination Maintenance Therapy with Both Bevacizumab and PARPi Provide Better Efficacy Than Bevacizumab Alone or Olaparib Alone in the First Line Treatment of Ovarian Cancer?
- Homologous recombination deficiency (HRD) positive: HR 0.33 (95% CI 0.25–0.45);
- BRCA1/2 mutation: HR 0.31 (95% CI 0.20–0.47); and
- HRD negative: HR 0.74 (95% CI 0.56–0.97). (Exploratory data analysis) [31] [strength of evidence IIIB].
3.6. Q6: Do Economic Analyses Exist That Can Guide Decision-Making Regarding Maintenance Therapy in Ovarian Cancer?
4. Future Bevacizumab Perspectives as Maintenance Therapy
5. Conclusions
- Based on a comparison of the strength of scientific evidence from available trials, it appears reasonable to consider using PARP inhibitors as first line maintenance therapy for all patients with advanced ovarian cancer who respond to platinum-based chemotherapy. For patients who do not respond to platinum or who experience recurrence during PARP inhibitor maintenance, bevacizumab may be more suitable as a second line option—it improves PFS and OS (confirmatory data). However, more trials are needed to validate the efficacy of bevacizumab in patients with molecularly confirmed angiogenic tumor profiles (bevacizumab predictors), regardless of the treatment line. The final conclusion of the manuscript provides detailed guidelines that can be summarized as follows:
- -
- Low strength of evidence supports the use of bevacizumab (Bev) in the first line treatment. It is recommended to preserve Bev for second line therapy; and
- -
- PARP inhibitors (PARPis) should be used as first line maintenance therapy for all patients who respond to platinum-based treatment.
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Study Type | Grade | Subtype Description |
---|---|---|
RTC systematic review | IA | Meta-analysis based on RTC systematic review results |
IB | RCT systematic review without meta-analysis | |
Experimental study | IIA | Well conducted randomised controlled trial, including pragmatic randomised controlled trial |
IIB | Well conducted clinical controlled trial with pseudorandomisation | |
IIC | Well conducted clinical controlled trial without randomisation | |
IID | One-arm study | |
Observational study with control group | IIIA | Systematic review of observational studies |
IIIB | Well conducted prospective cohort studies with simultaneous control group | |
IIIC | Well conducted prospective cohort studies with historic control group | |
IIID | Well conducted retrospective cohort studies with simultaneous control group | |
IIIE | Well conducted case-control study (retrospective) | |
Descriptive study | IVA | Case series—pretest/posttest * |
IVB | Case series—posttest ** | |
IVC | Other study of a group of patients | |
IVD | Case report | |
Expert opinion | V | Expert opinions based on clinical experience and reports from expert panels |
GOG218 [6] | ICON7 [7] | OCEANS [8] | AURELIA [9] | GOG213 [10] | |
---|---|---|---|---|---|
Primary Endpoint | PFS | PFS | PFS | PFS | OS |
Patients enrolled | Stage III (Incompletely resectable) or Stage IV after PDS | Stage I–III or Stage IVor Inoperable Stage III after PDS | Platinum-sensitive recurrent ovarian cancer (recurrence ≥6 months after completing platinum-based therapy) | Platinum-resistant recurrent ovarian cancer that had progressed ≤6 months after completing platinum-based therapy | Platinum-sensitive recurrent ovarian cancer |
Sample size | 1248 | 1528 | 484 | 361 | 748 |
Control arm | Cycles 1–6: C (AUC 6) + P (175 mg/m2) + PL, q3w Cycles 7–22: PL, q3w | Cycles 1–6: C (AUC 5 or 6) + P (175 mg/m2), q3w | Cycles 1–10: G (1000 mg/m2 on days 1 and 8) + C (AUC 4 on day 1) + PL (15 mg/kg on day 1), q3w | Cycles 1-PD: PAC (80 mg/m2 days 1, 8, 15, and 22 q4w); or TOP (4 mg/m2, days 1, 8, 15 q4w or 1.25 mg/m2, days 1–5 q3w); or PLD (40 mg/m2 day 1 q4w) | Paclitaxel (175 mg/m2) + carboplatin (AUC5) With or without SCS |
Experimental arm | Cycles 1–6: C (AUC 6) + P (175 mg/m2) + Bev (15 mg/kg), q3w Cycles 7–22: Bev (15 mg/kg), q3w | Cycles 1–6: C (AUC 5 or 6) + P (175 mg/m2) + Bev (7.5 mg/kg), q3w Cycles 7–18: Bev (7.5 mg/kg), q3w | Cycles 1–10: G (1000 mg/m2 on days 1 and 8) + C (AUC 4 on day 1) + Bev (15 mg/kg on day 1), q3w | Cycles 1-PD: Chemotherapy + Bev (15 mg/kg q3w or 10 mg/kg), q2w | Bev (15 mg/kg) + P (175 mg/m2) + Carboplatin (AUC5), followed by Bev maintenance. With or without SCS |
References | Line of Treatment | Primary Endpoint | PFS | OS | ORR (%) | ||||
---|---|---|---|---|---|---|---|---|---|
Median (Months) | HR | HR, 95% CI | Median (Months) | HR | HR, 95% CI | ||||
GOG218 | 1st line | PFS | 10.3 | 0.770 | 0.681– 0.870 | 39.3 | 0.885 | 0.750– 1.040 | NR |
14.1 | 39.7 | NR | |||||||
ICON7 | 1st line | PFS | 17.5 | 0.930 | 0.830– 1.050 | 58.6 | 0.990 | 0.850– 1.140 | 48.0 |
19.9 | 58.0 | 67.0 | |||||||
OCEANS | 2nd line | PFS | 8.4 | 0.484 | 0.388– 0.605 | 32.9 | 0.952 | 0.771– 1.176 | 57.4 |
12.4 | 33.6 | 78.5 | |||||||
AURELIA | 2nd line | PFS | 3.4 | 0.480 | 0.380– 0.600 | 13.3 | 0.850 | 0.660– 1.080 | 12.6 |
6.7 | 16.6 | 30.9 | |||||||
GOG213 | 2nd line | OS | 10.4 | 0.614 | 0.522– 0.722 | 37.3 | 0.827 | 0.683– 1.005 | NR |
13.8 | 42.2 | NR |
References | Line of Treatment | Patient Characteristics | Primary Endpoint | PFS | ||
---|---|---|---|---|---|---|
Median (Months) | HR | HR, 95% CI | ||||
SOLO1 olaparib | 1st line | FIGO III or IV (17%); BRCA mut-100%; PDS/IDS—63%/35%; R = 0 cm—76% | PFS | 13.8 | 0.33 | 0.25–0.43 |
56 | ||||||
PRIMA niraparib | 1st line | FIGO III or IV (35%); BRCA mut-30%; PDS/IDS—33%/67%; R = 0 cm—excluded | PFS | 8.2 | 0.62 | 0.50–0.76 |
13.8 | ||||||
PRIME niraparib | 1st line | FIGO III or IV (28%); BRCA mut-33%; PDS/IDS—53%/47%; R = 0 cm—75% | PFS | 8.3 | 0.45 | 0.34–0.60 |
24 | ||||||
ATHENA MONO rucaparib | 1st line | FIGO III or IV (24%); BRCA mut-22%; PDS/IDS—49%/51%; R = 0 cm—62% | PFS | 9.2 | 0.52 | 0.40–0.68 |
20.2 | ||||||
SOLO2 olaparib | 2nd line | Relapsed platinum-sensitive FIGO III or IV, BRCA mut—79% | PFS | 5.5 | 0.30 | 0.22–0.41 |
19.1 | ||||||
NOVA niraparib | >2rd line | Relapsed platinum-sensitive FIGO III or IV, BRCA wt—n = 350 | PFS | NR | 0.35 | 0.230–0.532 |
NR | ||||||
NOVA niraparib | >2rd line | Relapsed platinum-sensitive FIGO III or IV, BRCA mut—n = 203 (100%) | PFS | NR | 0.24 | 0.131–0.441 |
NR | ||||||
ARIEL3 rucaparib | >2rd line | Relapsed platinum-sensitive FIGO III or IV, BRCA mut—35%; | PFS | 5.4 | 0.36 | 0.30–0.45 |
10.8 | ||||||
ARIEL4 rucaparib | >2rd line | BRCA mut 100% Relapsed platin sensitive or platin resistant FIGO III or IV | PFS | 5.7 | 0.67 | 0.52–0.86 |
7.4 |
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Sznurkowski, J.J. To Bev or Not to Bev during Ovarian Cancer Maintenance Therapy? Cancers 2023, 15, 2980. https://doi.org/10.3390/cancers15112980
Sznurkowski JJ. To Bev or Not to Bev during Ovarian Cancer Maintenance Therapy? Cancers. 2023; 15(11):2980. https://doi.org/10.3390/cancers15112980
Chicago/Turabian StyleSznurkowski, Jacek Jan. 2023. "To Bev or Not to Bev during Ovarian Cancer Maintenance Therapy?" Cancers 15, no. 11: 2980. https://doi.org/10.3390/cancers15112980