Table 1.
Summary of All Patients Who Received One or More Targeted Therapeutic Agents
| Patient 1 | Patient 2 | Patient 3 | Patient 4 | Patient 5 | Patient 6 | Patient 7 | Patient 8 | Patient 9 | Patient 10 | Patient 11 | Patient 12 | |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age at FD | 74 | 42 | 58 | 46 | 57 | 37 | 61 | 26 | 64 | 58 | 49 | 52 |
| First-line therapy/prior treatment before targeted treatment | 1. Surgery, adj. RT; 2. Adj. RCTX; 3. CTX |
1. Surgery, adj. RCTX; 2. Surgery, RCTX | 1. Surgery; 2. RT; 3. CTX |
1. Surgery, adj. RT; 2. Surgery; 3. CTX |
1. Surgery, adj. RT; 2. Surgery, RCTX; 3. CTX |
1. Surgery, RCTX; 2. Surgery; 3. Surgery; 4. CTX |
1. Surgery; 2. CTX | 1. Surgery, RCTX; 2. Surgery; 3. CTX |
1. Surgery; 2. Surgery; 3. CTX |
1. Surgery; 2. RCTX; 3. Surgery + CTX; 4. Surgery; 5. RCTX 6. CTX |
1. Surgery, adj. local ablative RT; 2. RT; 3. stereotactic irradiation; 4. CTX |
1. Surgery; 2. RCTX; 3. CTX |
| Targeted therapeutic agents (in applied order) | 1. Bevacizumab 2. Erlotinib |
1. Erlotinib 2. Bevacizumab |
Erlotinib | Erlotinib | Erlotinib | 1. Bevacizumab 2. Pembrolizumab |
1. Bevacizumab 2. Pembrolizumab |
1. Bevacizumab 2. Pembrolizumab |
Bevacizumab | Bevacizumab | Bevacizumab | Bevacizumab |
| HPV status/EGFR Mut/PDL-1 status | HPV unknown/EGFR unknown | HPV unknown/EGFR wild type (PCR) | HPV unknown EGFR wild type (PCR) | HPV negative EGFR wild type (PCR) | HPV negative (p16−)/EGFR wild type (PCR) | HPV negative; PD-L1: CPS 1-5 | HPV unknown/PD-L1 CPS 60 | HPV negative/PD-L1 CPS unknown | HPV negative | HPV unknown | HPV unknown | HPV unknown |
| Best response | Bevacizumab: PR Erlotinib: SD |
Erlotinib: PR; Bevacizumab: PD | SD | PD | PR | Bevacizumab and pembrolizumab: PD | Bevacizumab: CR Pembrolizumab: SD |
Bevacizumab: PD Pembrolizumab: PD |
SD | CR | SD | SD |
| Side effects |
Bevacizumab: grade 3 CTCAE: high blood pressure Erlotinib: grade 1 CTCAE: exanthema |
Bevacizumab: no Erlotinib: grade 2 CTCAE: diarrhea, elevated liver enzymes, skin alterations (facial comedo) |
Grade 2 CTCAE: Skin problems, elevated liver enzymes | Grade 3 CTCAE: diarrhea with C. difficile infection, elevated liver enzymes Grade 2 CTCAE: skin problems (cutaneous rhagades) |
None |
Bevacizumab: grade 2 CTCAE: high blood pressure Pembrolizumab: grade 2 CTCAE: fatigue, lymphedema |
Bevacizumab: pericardial effusion Pembrolizumab: none |
Bevacizumab: grade 3 CTCAE: deep vein thrombosis Pembrolizumab: grade 2 CTCAE: lymphedema, hypothyroidism |
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| Grade 2 CTCAE: diarrhea, lymphedema, high blood pressure | Grade 3 CTCAE: arterial bleeding right groin 2 months after end of bevacizumab | None | None | |||||||||
| Dose reduction |
Bevacizumab: yes, due to high blood pressure resistant to therapy; Erlotinib: no |
Erlotinib and Bevacizumab: no | No | Yes, from 150 to 100 mg due to elevated liver enzymes | No | Bevacizumab and pembrolizumab: no | Bevacizumab and pembrolizumab: no |
Bevacizumab: yes, end of bevacizumab due to deep vein thrombosis Pembrolizumab: no |
No | No | No | No |
| Time to progression (months) |
Bevacizumab: 4 Erlotinib: 2 |
Erlotinib: 3; Bevacizumab: 4 | 6 | 2 | 4 | Bevacizumab and pembrolizumab: 4 |
Bevacizumab: 13
Pembrolizumab: 3 |
Bevacizumab: 6 Pembrolizumab: 3 |
Ongoing treatment | 12 | Ongoing treatment | 6 |
| Time to death from FD (months) | Unknown | 36 | 19 | 47 | Unknown | Unknown | Unknown | 40 | NA | 48 | NA | Unknown |
| Cause of death | Unknown | Tumor progression | Tumor progression | Kidney failure, tumor progression | Unknown | Unknown | Unknown | Tumor progression | NA | Tumor progression | NA | Unknown |
adj., adjuvant; CPS, combined positive score; CTCAE, Common Terminology Criteria for Adverse Events; EGFR, epidermal growth factor receptor; HPV, human papilloma virus; loc, local, dist, distant; rec, recurrence; PD, progressive disease; RD, recurrent disease; SD, stable disease; PR, partial response; FD, first diagnosis; CTX, chemotherapy; RT, radiotherapy; CRTX, chemoradiation.