| 1 | ABL1 | BCR-ABL1 Fusion | Acute lymphoblastic leukaemia; Chronic myelogenous leukaemia | Dasatinib | 20525995 | TGA approved. PBS listed. Second or third-line agent. Requires presence of the BCR-ABL transcript in either peripheral blood or bone marrow. |
| 1 | ABL1 | BCR-ABL1 Fusion | Acute lymphoblastic leukaemia; Chronic myelogenous leukaemia | Imatinib | 12637609 | TGA approved. PBS listed. First-line treatment. Requires presence of the BCR-ABL transcript. |
| 1 | ABL1 | BCR-ABL1 Fusion | Chronic myelogenous leukaemia | Nilotinib | 20525993 | TGA approved. PBS listed. Second or third-line agent. Requires cytogenetic evidence of the Philadelphia chromosome, or RT-PCR level of BCR-ABL transcript greater than 0.1%. |
| 1 | ABL1 | BCR-ABL1 Fusion and T315I
| Acute lymphoblastic leukaemia; Chronic myelogenous leukaemia | Ponatinib | 23190221
24180494 | TGA approved. PBS listed for acquired T315I mutation. Fourth line treatment. Requires cytogenetic evidence of the Philadelphia chromosome, or RT-PCR level of BCR-ABL transcript greater than 0.1%. PACE2. |
| 1 | ALK | EML4-ALK Fusion, Fusions | Non-small cell lung cancer | Alectinib | 28586279
28501140 | TGA approved. PBS listed. Requires fluorescence in situ hybridisation (FISH) testing for ALK gene rearrangement, defined as 15% (or greater) positive cells. In first-line setting, alectinib had a superior 12 months EFS of 68% vs crizotinib 49% (ALEX trial). In J-ALEX trial, the median progression-free survival (PFS) was NR (alectinib) vs 10.2 months (crizotinib). |
| 1 | ALK | EML4-ALK Fusion, Fusions | Non-small cell lung cancer | Ceritinib | 24670165
28126333
28602779 | TGA approved. PBS listed. Requires fluorescence in situ hybridisation (FISH) testing for ALK gene rearrangement, defined as 15% (or greater) positive cells. ASCEND-5 – In post-crizotinib and chemotherapy setting, Ceritinib had superior median progression-free survival (PFS) than 5.4 v docetaxel 1.6 months. ASCEND-4 – In first-line setting, Ceritinib has superior PFS 16.6 vs platinum chemotherapy 8.1 months. |
| 1 | ALK | EML4-ALK Fusion, Fusions | Non-small cell lung cancer | Crizotinib | 20979469
25470694 | TGA approved. PBS listed. Requires fluorescence in situ hybridisation (FISH) testing for ALK gene rearrangement, defined as 15% (or greater) positive cells. PROFILE1014 trial – in the first-line setting, Crizotinib had a superior progression-free survival (PFS) 10.9 vs chemotherapy 7.0 months. In the second-line setting, Crizotinib had longer PFS 7.7 vs docetaxel 3.0 months. No overall survival (OS) difference shown in either trials due to crossover of subgroups. |
| 1 | ALK | EML4-ALK Fusion, Fusions | Non-small cell lung cancer | Brigatinib | 30280657
32780660 | TGA approved. PBS listed. FDA approved. Phase 3 ALTA-1L trial. NCT02737501. N=275. Brigatinib demonstrated superior progression-free survival (PFS) (24.0 vs 11.0 months) and improved health-related quality of life in ALK inhibitor-naive ALK-positive non-small cell lung cancer patients, with consistent results across independent and investigator assessments. |
| 1 | ALK | EML4-ALK Fusion, Fusions | Non-small cell lung cancer | Lorlatinib | 30413378
33207094
10.1016/j.annonc.2020.08.2282 | TGA approved. PBS listed after progression on ALK inhibitor other than Crizotinib. Requires fluorescence in situ hybridisation (FISH) testing for ALK gene rearrangement, defined as 15% (or greater) positive cells. In Phase 3 trial vs crizotinib (CROWN): Overall survival (OS) was superior at12 months 78% vs 39%. |
| 1 | BCL2 | Overexpression | Chronic lymphocytic leukaemia | Venetoclax | 26639348
27178240 | TGA approved for R/R CLL with Chr 17p deletion or for whom there are no other suitable treatment options. |
| 1 | BCL2 | Overexpression | Chronic lymphocytic leukaemia | Venetoclax + Rituximab | 29562156 | TGA approved. Phase 3 trial. NCT02005471. N=389. Venetoclax-rituximab demonstrates significantly improved 2-year progression-free survival (85% vs 36%) compared to bendamustine-rituximab in relapsed or refractory chronic lymphocytic leukemia, with BCL2 overexpression being a characteristic of CLL cells. |
| 1 | BRAF | V600E | Colorectal adenocarcinoma | Encorafenib + Cetuximab | 31566309
33503393 | PBS listed. TGA approved. FDA approved. In Phase 3 BEACON colorectal cancer, overall survival (OS) for the encorafenib and cetuximab doublet was 8.2 months. The objective response rate (ORR) was 26%. |
| 1 | BRAF | V600E | Melanoma | Dabrafenib | 22735384 | TGA approved. PBS listed. However, single-agent not recommended. Median progression-free survival (PFS) 5.1 months (NCT01227889) vs dacarbazine 2.7 months. Rate of cutaneous SCC 6%. |
| 1 | BRAF | V600E | Melanoma | Vemurafenib | 21639808 | TGA approved. PBS listed. However, single-agent not recommended. BRIM-3 – higher response rate 48% v dacarbazine 5% with superior overall survival (OS) (HR 0.37). Cutaneous SCC 12%. |
| 1 | BRAF | V600E, V600K | Melanoma | Binimetinib + Encorafenib | 30219628
10.1200/JCO.2021.39.15_suppl.9507 | TGA approved. PBS listed. Phase 3 COLUMBUS trial. NCT01909453. Median overall survival was significantly longer with encorafenib plus binimetinib (33.6 months) compared to vemurafenib (16.9 months) in patients with BRAF(V600)-mutant melanoma. |
| 1 | BRAF | V600E, V600K | Melanoma | Dabrafenib + Trametinib | 25265492 | TGA approved. PBS listed. COMBI-D – Addition of trametinib to dabrafenib prolonged median progression-free survival (PFS) at 3 years (44 vs 32%). |
| 1 | BRAF | V600E, V600K | Melanoma | Vemurafenib + Cobimetinib | 25265494 | TGA approved. PBS listed. CoBRIM – Addition of cobimetinib to vemurafenib prolonged median progression-free survival (PFS) 9.9 vs 6.2 months. |
| 1 | BRCA1 | Oncogenic mutations | Ovarian cancer; Peritoneal serous carcinoma; Fallopian tube carcinoma | Niraparib | 31562799
39284381 | TGA approved. PBS listed. PRIMA/ENGOT-OV26/GOG-3012. In an updated analysis at median follow-up of 73.9 months, 5-year progression-free survival (PFS) rates favored niraparib overall (22% vs 12%) and in HRd patients (35% vs 16%). In BRCA-mutated patients showed PFS HR of 0.43, with 5-year PFS rates of 37% vs 14%. |
| 1 | BRCA1 | Oncogenic mutations | Ovarian cancer; Peritoneal serous carcinoma; Fallopian tube carcinoma | Olaparib | 30345884
34715071 | TGA approved. PBS listed. Requires identification of class 4 or 5 mutation (germline and somatic). SOLO1 trial - after initial platinum response, maintenance olaparib therapy prolonged progression-free survival (PFS) at 3 years (60% vs placebo 27%). Median PFS was 56.0 months in the olaparib arm versus 13.8 months in the placebo arm. |
| 1 | BRCA1 | Oncogenic mutations | Prostate cancer | Olaparib | 32343890
32955174 | TGA Approved. PBS listed for class 4 or 5 BRCA1 or BRCA2 gene mutation. Phase 3 PROfound trial. NCT02987543. (cohort A, N=160): Image-based progression-free survival (PFS) 7.4 mo (olaparib) v 3.6 months (control). Olaparib was associated with longer rPFS over control (HR, 0.22) and overall survival (OS) (HR, 0.63). RPFS benefit found in all zygosity subgroups. Risk of disease progression was similar for patients with germline (n = 61; HR, 0.08) and somatic (n = 51; HR, 0.16). |
| 1 | BRCA1 | Oncogenic mutations (germline) | Ovarian cancer; Peritoneal serous carcinoma; Fallopian tube carcinoma | Olaparib | 28754483
33743851 | TGA approved. PBS listed. Phase 3 SOLO2/ENGOT-Ov21 trial. NCT01874353. N=295. Olaparib maintenance therapy significantly improved progression-free survival (PFS) (19.1 vs 5.5 months) and provided a clinically meaningful overall survival (OS) benefit (51.7 vs 38.8 months) in patients with platinum-sensitive relapsed ovarian cancer and a BRCA1/2 mutation. |
| 1 | BRCA1 | Oncogenic mutations, Oncogenic mutations (germline) | Ovarian cancer; Peritoneal serous carcinoma; Fallopian tube carcinoma | Olaparib + Bevacizumab | 31851799 | TGA approved; FDA approved as maintenance therapy after first-line platinum-based chemotherapy. PAOLA-1 trial. Companion diagnostic for olaparib: MyChoice CDX. |
| 1 | BRCA2 | Oncogenic mutations | Ovarian cancer; Peritoneal serous carcinoma; Fallopian tube carcinoma | Niraparib | 31562799
39284381 | TGA approved. PBS listed. PRIMA/ENGOT-OV26/GOG-3012. In an updated analysis at median follow-up of 73.9 months, 5-year progression-free survival (PFS) rates favored niraparib overall (22% vs 12%) and in HRd patients (35% vs 16%). In BRCA-mutated patients showed PFS HR of 0.43, with 5-year PFS rates of 37% vs 14%. |
| 1 | BRCA2 | Oncogenic mutations | Ovarian cancer; Peritoneal serous carcinoma; Fallopian tube carcinoma | Olaparib | 30345884 | TGA approved. PBS listed. Requires identification of class 4 or 5 mutation (germline and somatic). SOLO1 trial - after initial platinum response, maintenance olaparib therapy prolonged progression-free survival (PFS) at 3 years (60% vs placebo 27%). |
| 1 | BRCA2 | Oncogenic mutations | Prostate cancer | Olaparib | 32343890
32955174 | TGA Approved. PBS listed for class 4 or 5 BRCA1 or BRCA2 gene mutation. Phase 3 PROfound trial. NCT02987543. (cohort A, N=160): Image-based progression-free survival (PFS) 7.4 mo (olaparib) v 3.6 months (control). Olaparib was associated with longer rPFS over control (HR, 0.22) and overall survival (OS) (HR, 0.63). RPFS benefit found in all zygosity subgroups. Risk of disease progression was similar for patients with germline (n = 61; HR, 0.08) and somatic (n = 51; HR, 0.16). |
