Table 3.
Patients with disease control under off-label treatment since 2017.
| Cancer Type | Rational for Treatment Recommendation | Board Recommendation | EL | L | R | PFS2 (Week) | PFS1 (Week) | PFSr | Outcome |
|---|---|---|---|---|---|---|---|---|---|
| Adrenocortical Carcinoma | Positive IO-Panel (TPS 2%, CPS 3, IC-Score 0). Chromosomal instability (CNV in 16 oncogenes and 28 tumor suppressor genes) | Study: Nivolumab for rare cancers (NCT02832167) | m2C | off | SD | 36 | 37 | 1.0 | SD for 36 weeks |
| Tumor mutational burden high (11.07/Mb) | Pembrolizumab | m2C | off | SD | 53 | 3 | 17.5 | SD for 53 weeks | |
| CRC | Positive IO-Panel (TPS 5%, CPS 10, IC-Score 1). | Combination of atezolizumab and cobimetinib | m2C | off | PR | 76 | 11 | 6.9 | PR for 76 weeks then switch to best supportive care |
| CUP | Signet ring cell carcinoma of unknown primary site with chromosomal Instability incl. a high copy number gain in EGFR (×338). | Combination of cetuximab and FOLFIRI | m2A | off | SD | 25 | 31 | 0.8 | SD for 25 weeks the PD with new ascites. Switch to Combination of paclitaxel and ramucirumab |
| Histiocytosis | Erdheim Chester disease with BRAF-V600E mutation. | BRAF-inhibition with vemurafenib or dabrafenib | m1B | off | PR | >133 | 51 | >2.6 | Initial treatment with vemurafenib. Due to toxicity switch to dabrafenib after 10 weeks. Very good PR in cMRI after 39 weeks therefore switch to maintenance therapy with peg-INF. PR still ongoing |
| Meningioma | Anaplastic meningioma. IHC shows strong staining for somatostatin on 100% of tumor cells | Octreotide | m3 | off | SD | 18 | n.a. | n.a. | SD for 18 weeks then PD with new resection. PFS1 n.a. since no prior systemic therapy received. Only surgery and radiation therapy |
| Mesothelioma | Despite negative IO-Panel (TPS < 1%, CPS 10, IC-Score 1) data show response to checkpoint-Inhibition [62] | Pembrolizumab | m1C | off | SD | 32 | 56 | 0.6 | SD for 32 weeks then patient death |
| PXA | Pleomorphic xanthoastrocytoma with BRAF V600E mutation | BRAF-Inhibition with combination of dabrafenib and trametinib | m1C | off | CR | >64 | n.a. | n.a. | CR for 64 weeks and ongoing. PFS1 n.a. since no prior systemic therapy received. Only surgery and radiation therapy. |
| Prostate | Deleterious BRCA2 mutation. | Platinum-based chemotherapy followed by olaparib | m2A | off | SD | 31 | 7 | 4.5 | SD for 31 weeks then PD |
| Salivary | IHC shows strong androgen receptor staining in 90% of tumor cells. | Combination of degarelix and bicalutamide | m1C | off | CR | 66 | n.a. | n.a. | CR for 66 weeks then PD with new metastasis. PFS1 n.a. after resection (R0) and adjuvant radiochemotherapy |
| Sarcoma | WES shows BRCAness of 29% | Combination of olaparib and trabectedine | m3 | off | SD | 6 | 4 | 1.3 | SD in first staging after 2 weeks. Due to pain initiation of palliative radiation therapy with consecutive esophagitis and pancytopenia resulting in death at 6 weeks |
| Thyroid (anaplastic) |
Positive IO-Panel (TPS 5%, CPS 9, IC-Score 1). Study availability | Combination of pembrolizumab and lenvatinib | m2C | off | PR | >53 | 16 | >3.3 | PR for 53 weeks and ongoing |
| (anaplastic) | Positive IO-Panel (TPS > 80%, intratumoral TILs) | Pembrolizumab | m2C | off | CR | 25 | 7 | 3.0 | CR but died due to pulmonary bleeding at 21 weeks |
| (anaplastic) | Positive IO-Panel (TPS 5%, intratumoral TILs). Chromosomal instability with strong amplification of PDGFRA (×28) and PDGFB (×29) | Combination of pembrolizumab and lenvatinib | m2C | off | CR | 83 | 16 | 3.9 | CR for 83 weeks and ongoing. Lenvatinib was discontinued after 52 weeks. |
| (anaplastic) | RNA-Seq shows upregulation of FGFR3 signaling pathway | FGFR3-Inhibition with lenvatinib | m3 | off | SD | 11 | n.a. | n.a. | Good clinical response with regressive local relapse and significant clinical improvement. Therapy was discontinued after 14 weeks due to weight loss, then PD and death. |
| (medullary) | RET Met918Thr Mutation | Selpercatinib | m1A | off | PR | 35 | 15 | 2.3 | Radiologic PR. Serologic decrease of calcitonin from 8554 pg/mL to 12 pg/mL. Response ongoing. |
Forty-one out of 488 patients showed disease control under the recommended treatment. Progression free survival (PFS1, PFS2) was determined according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Median PFS2 (53 weeks; range 6–238 weeks) was significantly longer than median PFS1 (16 weeks; range 3–16 weeks; p = 0.003). Here we list the yet unpublished off-label responders (16 patients) that were discussed between March 2017 and December 2018. Relevant diagnostic results leading to a board recommendation, level of evidence (EL), label (L), treatment response (R), progression free survival (PFS1, PFS2), progression free survival ratio (PFS2/PFS1 = PFSr) and outcome are shown. PFS1 and PFSr could not be evaluated for four patients since they did not receive a prior systemic treatment. PR: partial response. SD: stable disease. n.a.: not applicable. CUP: cancer of unknown primary. IO-Panel: Immuno-oncology panel. TPS: Tumor Proportion Score. CPS: Combined positive score. IC-Score: Immune cell score. TILs: Tumor infiltrating lymphocytes. CNV: Copy number variation. PXA: Pleomorphic xanthoastrocytoma.