Table 4.
Selected ongoing clinical trials of PI3K/AKT/mTOR inhibitors involving PIK3CA mutation as a selection population biomarker.
| Drug | Target(s) | Trial | Population (n) | Results | Toxicities (Most Common) |
Ref. |
|---|---|---|---|---|---|---|
| Temsirolimus | mTORC1 | Global ARCC (vs. INF-α vs. combination) |
Untreated, mRCC (n = 626) |
↑ OS (10.9 vs. 7.3 months; p = 0.008) ↑ PFS in the temsirolimus monotherapy (p < 0.001) |
Rash, HG, HL; mild | [5] |
| Everolimus | mTORC1 | RECORD-I (vs. placebo) |
Previously treated, mRCC (n = 272) |
↑ PFS (4.0 vs. 1.9 months; p < 0.0001) No significant improvement in OS or in ORR |
Stomatitis, rash, fatigue, pneumonitis, diarrhea | [6] |
| RADIANT-3 (vs. placebo) |
Advanced pancreatic NET (n = 410) |
↑ PFS (mPFS 11.0 vs. 4.6 months; p < 0.001) No clear ORR benefit |
Stomatitis, rash, fatigue, pneumonitis, diarrhea | [7] | ||
| RADIANT-4 (vs. placebo) |
Other NET (n = 302) |
↑ PFS (11.0 vs. 3.9 months; p < 0.00001) No clear ORR benefit |
Stomatitis, rash, fatigue, pneumonitis, diarrhea | [8] | ||
| +AI | BOLERO-2 (vs. placebo + AI) |
HR+/HER2− breast cancer (n = 724) |
↑↑ ORR (9.5% vs. 0.5% p < 0.001) ↑ mPFS (6.9 vs. 2.8 months; p < 0.001) |
Stomatitis, rash, fatigue, pneumonitis, diarrhea | [9] | |
| Copanlisib | Pan-PI3K | CHRONOS-1 (vs. placebo) | r/r B-NHL, Macroglobulinemia (n = 142) |
ORR of 59% (12% CR and 47% PR), with a mPFS of 11.2 months | HG, nausea | [12] |
| Idelalisib + rituximab |
PI3K-δ |
NCT01539512 (vs. placebo+ rituximab) |
Relapse CLL (n = 220) |
ORR (81% vs. 13%), ↑ PFS at 24 weeks (93% vs. 46%; p < 0.001), ↑ 1-year OS (92% vs. 80%; p = 0.002). |
Diarrhea, rash, immune-mediated hepatitis/ pneumonis |
[14] |
|
NCT01282424 (vs. placebo) |
r/r B-NHL (FL) and SLL (n = 125) |
ORR: 54% in FL patients and 58% in SLL (p < 0.001) | Diarrhea, rash, immune-mediated hepatitis, and pneumonitis | [15] |
mRCC: Metastatic renal cell carcinoma; OS: Overall survival; PFS: Progression-free survival; mPFS: median PFS; ORR: Objective Response Rate; r/r: Recurrent/relapsed; NET: Neuroendocrine tumors; CLL: Chronic lymphocytic leukemia; SLL: Small lymphocytic leukemia; B-NHL: B-non Hodgkin lymphoma; HR: Hormone receptor; FL: Follicular lymphoma.