Compassionate Use Program of Ipilimumab and Nivolumab in Intermediate or Poor Risk Metastatic Renal Cell Carcinoma: A Large Multicenter Italian Study
Abstract
:Simple Summary
Abstract
1. Introduction
2. Materials and Methods
2.1. Inclusion Criteria
- -
- Histological confirmation of RCC;
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- Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2;
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- Advanced (not amenable to curative surgery or radiation therapy)/metastatic RCC Intermediate or poor IMDC score;
- -
- No prior treatment for metastatic disease;
- -
- Prior treatment with checkpoint inhibitors as adjuvant therapy;
- -
- active or suspected autoimmune disease requiring the use of systemic immunosuppressive agents or steroids (>10 mg of prednisone or equivalents);
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- active (untreated) brain metastases requiring steroid therapy (>10 mg/day prednisone equivalents);
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- any other conditions requiring systemic treatment with corticosteroids (>10 mg daily of prednisone or equivalents) or other immunosuppressive medications within 14 days prior to the first dose of IPI-NIVO
- -
- any positive test result for hepatitis B or hepatitis C virus indicating presence of virus, e.g., Hepatitis B surface antigen (HBsAg) positive, or Hepatitis C antibody (anti-HCV) positive (except if HCV-RNA negative);
- -
- a known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS);
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- major surgery (e.g., nephrectomy) less than 28 days prior to the first dose.
2.2. Treatment Regimen and Evaluation of Response
2.3. Statistical Analysis
3. Results
3.1. Patients’ Charactheristics
3.2. Early Interruption of Treatment
3.3. Overall Survival
3.4. Progression-Free Survival
3.5. Response Rate
3.6. Safety
3.7. Second-Line Therapy
4. Discussion
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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n = 324 | |||
---|---|---|---|
Age, median (range) 70–79 years; ≥80 years | 62 years (24–87) 72 pts (22.5%)/14 pts (4.3%) | ||
Gender | 240 Males (74.1%)/84 Females (25.9%) | ||
n | % | ||
Symptoms | yes | 128 | 39.5 |
no | 196 | 60.5 | |
ECOG PS | 0 | 177 | 55 |
1 | 115 | 36 | |
2 | 32 | 10 | |
BMI | ≥25 kg/m2 | 143 | 44.1 |
<25 kg/m2 | 181 | 55.9 | |
Autoimmune disease | yes | 10 | 3.1 |
no | 314 | 96.9 | |
Nephrectomy | before treatment | 211 | 65.1 |
during treatment | 8 | 2.5 | |
None | 105 | 32.4 | |
Histology | clear cell | 269 | 83.0 |
papillary | 21 | 6.5 | |
chromophobe | 8 | 2.5 | |
unclassified | 26 | 8.0 | |
WHO grade | G1-2 | 48 | 14.8 |
G3-4 | 130 | 40.1 | |
NA | 146 | 45.1 | |
Metastases at diagnosis | yes | 200 | 61.7 |
no | 95 | 29.3 | |
undefined | 29 | 9 | |
Sites of metastases | lung | 231 | 71.3 |
bone | 100 | 30.9 | |
liver | 59 | 18.2 | |
brain | 26 | 8.0 | |
pancreas | 15 | 4.6 | |
other | 80 | 24.7 | |
IMDC risk score | Intermediate | 221 | 68.2 |
1 risk factor | 119 | 36.7 | |
2 risk factors | 102 | 31.5 | |
poor | 103 | 31.8 |
n = 324 | ||
---|---|---|
Number of cycles of IPI-NIVO received | n | % |
1 | 37 | 11.4 |
2 | 33 | 10.2 |
3 | 34 | 10.5 |
4 (as planned) | 220 | 67.9 |
Reason for early discontinuation | n | % |
Progression | 49 | 15.1 |
Adverse events | 55 | 17.0 |
First Evaluation after IPI-NIVO | Additional Responses during Nivolumab Monotherapy | Overall Response Rate | |
---|---|---|---|
Response | Patients (%) | Patients (%) | Patients (%) |
Complete response | 5 (1.9) | 3 (1.1) | 8 (2.8) |
Partial response | 76 (28.1) | 22 (7.8) | 98 (34.8) |
Stable | 96 (35.6) | - | 80 (28.4) |
Progression | 93 (34.4) | - | 96 (34.0) |
Total evaluable | 270 (100) | - | 282 (100) |
AE | n = 55 | % |
---|---|---|
Gastrointestinal | 18 * | 32.7 |
Hepatic | 8 † | 14.5 |
Pulmonary | 5 | 9.1 |
Pancreatic | 5 | 9.1 |
Neurological | 4 | 7.3 |
Asthenia | 2 | 3.6 |
Cardiac | 1 | 1.8 |
Endocrine | 1 | 1.8 |
Allergic event | 1 | 1.8 |
Skin toxicity | 1 | 1.8 |
Renal | 1 # | 1.8 |
Anemia | 1 | 1.8 |
Others | 12 | 21.8 |
irAE | Grade 1–2 (%) | Grade 3–4 (%) | Grade 5 (%) |
---|---|---|---|
Gastrointestinal | 39 (12.0) | 21 (6.5) | 2(0.6) |
Hepatic | 12 (3.7) | 16 (4.9) | 1 (0.3) |
Pulmonary | 4 (1.2) | 8 (2.5) | 0 |
Pancreatic | 4 (1.2) | 9 (2.8%) | 0 |
Neurological | 13 (4.0) | 6 (1.9) | 0 |
Asthenia | 15 (4.6) | 2 (0.6) | 0 |
Cardiac | - | 1 (0.3) | 0 |
Thyroid | 51 (15.7) | 4 (1.2) | 0 |
Hypophysitis | 5 (1.5) | 5 (1.5) | 0 |
Skin | 54 (16.7) | 5 (1.5) | 0 |
Anemia | 3 (0.9) | 2 (0.6) | 0 |
Others | 3 (0.9%) | 8 (2.5%) | 1 (0.3%) |
Total | 203 (62.7) | 67 (26.9%) | 4 (1.2%) |
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Basso, U.; Paolieri, F.; Rizzo, M.; De Giorgi, U.; Bracarda, S.; Antonuzzo, L.; Atzori, F.; Cartenì, G.; Procopio, G.; Fratino, L.; et al. Compassionate Use Program of Ipilimumab and Nivolumab in Intermediate or Poor Risk Metastatic Renal Cell Carcinoma: A Large Multicenter Italian Study. Cancers 2022, 14, 2293. https://doi.org/10.3390/cancers14092293
Basso U, Paolieri F, Rizzo M, De Giorgi U, Bracarda S, Antonuzzo L, Atzori F, Cartenì G, Procopio G, Fratino L, et al. Compassionate Use Program of Ipilimumab and Nivolumab in Intermediate or Poor Risk Metastatic Renal Cell Carcinoma: A Large Multicenter Italian Study. Cancers. 2022; 14(9):2293. https://doi.org/10.3390/cancers14092293
Chicago/Turabian StyleBasso, Umberto, Federico Paolieri, Mimma Rizzo, Ugo De Giorgi, Sergio Bracarda, Lorenzo Antonuzzo, Francesco Atzori, Giacomo Cartenì, Giuseppe Procopio, Lucia Fratino, and et al. 2022. "Compassionate Use Program of Ipilimumab and Nivolumab in Intermediate or Poor Risk Metastatic Renal Cell Carcinoma: A Large Multicenter Italian Study" Cancers 14, no. 9: 2293. https://doi.org/10.3390/cancers14092293