The American Society of Clinical Oncology (ASCO) recently wrapped up its annual meeting in Chicago, IL. This year’s meeting gathered approximately 40,000 attendees; and featured thousands of presentations showcasing the newest developments in cancer research. According to ASCO, there were more than 7000 abstracts/sessions, 3400+ of which were posters (including TPS), and 300+ were oral.

The highlights and top stories

What’s currently hot in clinical oncology? Unsurprisingly, immune checkpoint inhibitors—as monotherapy or in combination—were high on the list, accounting for more than 150 abstracts. KEYNOTE-001 5-year data in patients with advanced non-small cell lung carcinoma (NSCLC) further solidify the confidence in and utility of checkpoint inhibitors. Encouraging data from the CheckMate studies were also on display, including promising efficacy and safety results in hepatocellular carcinoma (-040) and renal cell carcinoma (-920), as well as favorable long-term survival data in melanoma (-067 and -069). The recent successes seen from PD-1/PD-L1 combination therapies were echoed in abstracts that ranged the gauntlet from NSCLC to melanoma, to many other solid tumors, as well as lymphoma. Also notable, breast cancer enters the immunotherapy era. This trend can also be seen on ClinicalTrials.gov. Immune checkpoint inhibitor combination ‘partners’ appear to include PARP inhibitors (PARPi) and various TKIs.

The first PARPi, olaparib, was approved in 2014 for BRCA-mutated advanced ovarian cancer. In the intervening years, rucaparib, niraparib, and talazoparib have also been approved for multiple tumor types (eg, epithelial ovarian, fallopian tube, primary peritoneal, and breast cancer). PARPis have been approved for tumors that bear either germline or somatic BRCA mutations and made noticeable noise at ASCO 2019, for both ovarian and breast cancer. Throughout more than 50 abstracts, PARPi use in adjuvant or neoadjuvant therapies was popular, as were PARPi combinations with molecular targeted agents, other DDR agents, and immune checkpoint inhibitors. One PARPi abstract of note was that of the phase 3 POLO trial of olaparib as maintenance therapy for patients with gBRCAm and metastatic pancreatic cancer, which showed promising results—nearly doubling progression-free survival (PFS).

Breast cancer (~401 abstracts), NSCLC (~392 abstracts), and prostate cancer (~188 abstracts) were also very hot this year, as can be expected. In breast cancer, an abstract on the phase 3 MONALEESA-7 trial showed that adding a CDK4/6 inhibitor (to hormone therapy) in premenopausal patients with advanced HR+/HER2- tumors produced a significant increase in PFS. These results are particularly impactful because this demographic (premenopausal, or younger women) is seeing an increase in the incidence of advanced breast cancer.

In NSCLC, an emphasis was on driver mutations, with one third of the NSCLC abstracts dealing with driver mutations, and almost half of those abstracts focused on EGFR-mutations. One presentation highlighted the results of a phase 3 trial, showing the addition of chemotherapy to gefitinib (a TKI) doubled PFS and significantly improved overall survival in patients with newly diagnosed EGFRm NSCLC.

One of the most anticipated announcements at ASCO 2019 was the preliminary clinical results from a phase 1 trial investigating AMG 510, the first KRASG12C inhibitor to reach clinical studies. KRAS was identified more than 30 years ago as an oncogene but had elusively remained “undruggable.” Early data from the study showed favorable results in NSCLC and colorectal cancer, with tumor shrinkage seen in 5/10 NSCLC patients.

The use of targeted therapies was also seen in pediatric cancer, including results for trials of LOXO-292 and entrectinib. LOXO-292 targets mutated RET, which is found in many solid tumors, and was shown to have encouraging results in a small number of pediatric patients. Hence, a newly initiated trial in progress was announced. Entrectinib, which targets TrkA/B/C, ROS1, and ALK displayed very encouraging results, including rapid and durable responses in all pediatric patients enrolled with recurrent or refractory CNS or solid tumors that harbor the aforementioned targeted mutations. Several other abstracts investigating targets that we will be keeping our eyes on include: APRIL; BET; CDKs; ErbB3; FGFR3; FLT3; IDH1/2; IL2; JAK2; mTOR; NaPi2b, Notch; RET; ROR1; selectins; TIE2; and Tsp1.

Conference attendees were also excited for news on cellular therapies. Advances in CAR T cell therapy in hematological cancers were big again this year. Data of trials of CAR T cell therapy targeting CD19 in chronic lymphocytic leukemia (JCAR017) and acute lymphoblastic leukemia (KTE-X19) showed good results. In addition, positive results were also seen with CAR T cells in solid tumors (small-cell lung, gastric, pancreatic, and liver).

Other intriguing abstracts on new cellular-based therapies included bispecific T cell engagers (BiTE) and the individually engineered tumor infiltrating lymphocytes (TIL). BiTEs are bispecific molecules that bind to cytotoxic T cells on one arm and tumor proteins on the other arm. Once bound to both targets, the T cell can recognize the tumor cell. BiTEs were showcased across nearly half a dozen abstracts (8007, e19041, TPS2071, TPS8577, 5034) in hematologic malignancies and solid tumors, including multiple myeloma, B-cell non-Hodgkin lymphoma, glioblastoma, small-cell lung cancer, and prostate cancer. TIL therapy relies on removing a portion of a patient’s tumor, isolating lymphocytes within the tumor for ex vivo expansion, and infusing the expanded TIL into the patient. TIL abstracts included preliminary results from clinical trials of their safety and efficacy in cervical cancer and melanoma. Preliminary results of TIL treatment for melanoma, lifileucel, showed that after nine-months of follow-up, median duration of response had not yet been determined.

What comes next?

ASCO 2019 may be over, but there are still plenty of related events happening around the country. Check out the 2019 Best of ASCO Meetings to see if any are taking place near you, and check out this calendar for other oncology-related meetings!

In addition, keep checking wiesenmed.com for more coverage from events like ASH, ESMO, EHA, and more!

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