Notable Study Results Presented at ESMO Congress 2019

Encouraging advancements in the oncology space took center stage at the European Society for Medical Oncology Congress 2019, where new and ongoing practice-changing data were presented.

The meeting, held in Barcelona, Spain, from September 27 to October 1, highlighted findings from a plethora of studies across the cancer spectrum that could potentially have an impact on patient care. This year, particular clinical advancements in breast, lung, and ovarian cancers were heavily represented among the late-breaking abstract presentations.

Although many developments were highlighted, these were some of the most notable study results to come out of the conference.

Significant Benefit With CDK4/6 Inhibitors in Advanced Breast Cancer^1,2

The MONALEESA-3 and MONARCH 2 studies demonstrated improved overall survival (OS) in women with hormone receptor—positive, HER2-negative advanced breast cancer.

MONALEESA-3

Compared with fulvestrant (Faslodex) alone, the cyclin-dependent kinase (CDK) 4/6 inhibitor ribociclib (Kisqali) plus fulvestrant significantly improved OS in the first and second lines in postmenopausal patients with hormone receptor—positive, HER2-negative advanced breast cancer. Investigators observed the benefits with ribociclib plus fulvestrant in women previously untreated with hormonal therapy as well as in those who had become resistant to endocrine therapy.

According to Dennis J. Slamon, MD, PhD, director of clinical/translational research, Revlon/University of California, Los Angeles, and the Women’s Cancer Research Program, Jonsson Comprehensive Cancer Center, the combined data set of MONALEESA-3 and -7, which included approximately 1400 patients, represents the largest body of evidence of OS benefit for any CDK4/6 inhibitor.

MONARCH 2

Results of MONARCH 2 showed statistically and clinically meaningful improvement in OS with the CDK4/6 inhibitor abemaciclib (Verzenio) plus fulvestrant in pre-, peri-, and postmenopausal women with hormone receptor—positive, HER2-negative advanced breast cancer resistant to hormonal therapy.

The study, presented by lead author George W. Sledge Jr, MD, professor of medicine (oncology) and chief of the Division of Oncology at Stanford University Medical Center in California, included a median OS benefit of 9.4 months. This benefit was consistent across subgroups, including patients with poor prognostic factors, such as visceral metastasis and primary endocrine therapy resistance, Sledge reported.

Additionally, 17% of patients in the abemaciclib arm remained on treatment versus 4% in the placebo arm after a median follow-up of 47.7 months at the time of analysis.

Nivolumab/Low-Dose Ipilimumab: A Potential Chemotherapy-Sparing Option in Lung Cancer³

Referred to as “practice-changing” data, results from the CheckMate 227 trial showed that the combination of nivolumab (Opdivo) and low-dose ipilimumab (Yervoy) may offer a chemotherapy-free, first-line option for patients with advanced non—small cell lung cancer (NSCLC).

The phase 3 study included patients with stage IV or recurrent NSCLC who had received no previous treatment. According to the data, patients with PD-L1 ≥1% treated with nivolumab plus ipilimumab had a median OS of 17.1 months (95% CI, 15.0-20.1) compared with 14.9 months (95% CI, 12.7-16.7) in the chemotherapy group (HR, 0.79; 97.72% CI, 0.65- 0.96; P = .007).

The study also found an OS benefit with nivolumab plus ipilimumab versus chemotherapy in patients with PD-L1 <1% and in all randomized patients.

Niraparib in Frontline Maintenance Setting for Ovarian Cancer⁴

Results of the PRIMA/ENGOT-OV26/GOG-3012 phase 3 study showed that poly—(ADP-ribose) polymerase (PARP) inhibitor niraparib (Zejula) monotherapy significantly improved progression-free survival (PFS) in patients with advanced ovarian cancer following response to first-line chemotherapy.

Niraparib treatment resulted in a 38% reduction in the risk of disease progression or death in the overall population (HR, 0.62; 95% CI, 0.50-0.75; P <.001). The data demonstrated a clinically meaningful reduction in risk of progression in women with BRCA mutation—positive tumors, homologous recombination–deficient BRCA wild-type tumors, and homologous recombination–proficient tumors.

In an interview with Pharmacy Times®, Mansoor Raza Mirza, MD, chief oncologist at Copenhagen University Hospital in Denmark, described the data on PARP inhibitors from several studies presented at the congress as “unprecedented,” adding, “We have not seen such results in the last 30 years, so this is really changing the history.”

First Targeted Therapy to Improve Outcomes in Cholangiocarcinoma⁵

For the first time, a targeted therapy has improved outcomes in patients with cholangiocarcinoma, a rare, aggressive, and often fatal subtype of bile duct cancer.

Ivosidenib (Tibsovo), an oral isocitrate dehydrogenase 1 (IDH1) inhibitor, showed clinical benefit in the phase 3 ClarIDHy trial, significantly improving PFS and demonstrating a promising OS trend. This study is the first to demonstrate clinical benefit of targeting mutant IDH1 in patients with advanced IDH1-mutated cholangiocarcinoma, said the authors.

According to the results, the median PFS was 2.7 months for patients treated with ivosidenib compared with 1.4 months with placebo (HR, 0.37; 95% CI, 0.25-0.54; P <.001). At 6 months, the median PFS rate was 32% with ivosidenib, whereas no patients who received placebo were free from progression at this point.

Additionally, the data pointed to a trend favoring ivosidenib in OS, with a median OS of 10.8 months for ivosidenib versus 9.7 months for placebo (HR, 0.69; 1-sided P = .06). After adjusting the OS results to account for 57% of patients in the placebo arm who crossed over to the ivosidenib cohort, patients on placebo showed an OS of 6 months.

REFERENCES

• MONARCH 2: overall survival of abemaciclib plus fulvestrant in patients with HR+, HER2- advanced breast cancer. Presented at: European Society for Medical Oncology Congress 2019; September 29, 2019; Barcelona, Spain. Abstract LBA6_PR.
• Overall survival results from the phase 3 MONALEESA-3 study of fulvestrant ± ribociclib in postmenopausal patients with HR+/HER2- advanced breast cancer. Presented at: European Society for Medical Oncology Congress 2019; September 29, 2019; Barcelona, Spain. Abstract LBA7_PR.
• Peters S, Ramalingam SS, Paz-Ares L, et al. Nivolumab (NIVO) + low-dose ipilimumab (IPI) vs platinum-doublet chemotherapy (chemo) as first-line (1L) treatment (tx) for advanced non-small cell lung cancer (NSCLC): CheckMate 227 part 1 final analysis. Presented at: European Society for Medical Oncology Congress 2019; September 27-October 1, 2019; Barcelona, Spain. Abstract LBA4_PR.
• González Martin A, Pothuri B, Vergote IB, et al. Niraparib therapy in patients with newly diagnosed advanced ovarian cancer (PRIMA/ENGOT-OV26/GOG-3012 study). Presented at: European Society for Medical Oncology Congress 2019; September 27-October 1, 2019; Barcelona, Spain.
• Abou-Alfa GK, Mercade M, Javie M, et al. ClarIDHy: a global, phase 3, randomized double-blind study of ivosidenib (IVO) vs placebo in patients with advanced cholangiocarcinoma (CC) with an isocitrate dehydrogenase 1 (IDH1) mutation. Presented at: European Society for Medical Oncology Congress 2019; September 27-October 1, 2019; Barcelona, Spain.