October 20, 2020 Nichole Tucker
Several late-phase results were shared during the European
Society of Medical Oncology Virtual Congress in gynecologic malignancies, but
the data presented generated excitement about the number of novel options for
patients after initial treatment.
Several late-phase
results were shared during the European Society of Medical Oncology (ESMO)
Virtual Congress in gynecologic malignancies, but the data presented generated
excitement about the number of novel options for patients after initial
treatment.
Updated findings in
ovarian cancer demonstrated continued benefit for PARP inhibition as
maintenance therapies following frontline treatment in advanced ovarian cancer
in the phase 3 SOLO-1 trial (NCT01844986) using the PARP inhibitor olaparib
(Lynparza) and in the phase 2 PRIMA/ENGOT-OV26/GOG-3012 ([PRIMA], NCT02655016),
which utilized the PARP inhibitor niraparib (Zejula).
Enthusiasm also
surrounded a potential new approach in cervical cancer from the phase 2
innovaTV 204/GOG-3023/ENGOT-cx6 study ([innovaTV], NCT03438396), which explored
treatment with the investigational antibody-drug conjugate tisotumab vedotin.
The SOLO-1 Study
The longest duration
of follow-up for any PARP inhibitor in the previously untreated advanced
ovarian cancer setting was performed in the phase 3, randomized, double-blind,
placebo-controlled, multicenter SOLO-1 trial, in which olaparib maintenance was
given to patients with BRCA mutations. The 5-year follow-up
results were presented at ESMO by Susan Banerjee, MD, PhD, FRCP, consultant
medical oncologist and research lead for the Gynecology Unit at The Royal
Marsden.1
“The updated analysis
after 5 years of follow-up shows that the benefit of olaparib continues
substantially beyond the end of treatment,” Banerjee told Targeted
Oncology in an interview.
Out of the 391
patients assessed, 260 received olaparib maintenance and 131 received placebo
for up to 2 years or until progressive disease (PD). Olaparib maintenance first
demonstrated an improvement in progression-free survival (PFS) in the primary
analysis with the median PFS not yet reached in the olaparib arm at this
timepoint compared with 13.8 months in the placebo arm (HR, 0.30; 95% CI,
0.23-0.41).
The median follow-up
for the updated analysis was 4.8 years in the olaparib arm compared with 5.0
years in the placebo arm. The results showed PFS events in 45% of the
olaparib-treated population versus 76% of the placebo population. The median
PFS observed with olaparib maintenance was 56.0 months compared with 13.8
months in the placebo arm (HR, 0.33; 95% CI, 0.25-0.43).
“These are very
encouraging results that will help us explain the potential benefits of maintenance
olaparib in patients with BRCA mutations,” said Banerjee.
The PRIMA Study
A new analysis of the
phase 3 randomized, double-blind, placebo-controlled, multicenter PRIMA trial
presented during ESMO by Giorgio Valabrega, MD, investigated the potential
difference in efficacy and safety by age of niraparib maintenance after
chemotherapy in patients with advanced ovarian cancer.
“The key findings of
our trial were that there is no difference in terms of safety and efficacy by
adding niraparib to chemotherapy. Also, the [adverse events] that were observed
in patients above 65 and 75 [years of age] in comparison to younger patients
are not different,” Valabrega, associate professor, University of Torino School
of Medicine, told Targeted Oncology in an interview.
The subanalysis
included 444 patients from the original PRIMA study who were 65 years of age or
younger. Of the patients included in this analysis, 297 received niraparib and
147 received placebo.2
A second cohort from
the analysis included 289 patients aged 65 or older. Among this group, 76
patients were 75 years or older. One hundred ninety of the patients received
niraparib maintenance while 99 received placebo in the younger cohort and of
those 75 years or older, 54 patients received niraparib and 22 received
placebo.
Demonstrating
consistency with the primary analysis which showed a median PFS on 13.8 months
with niraparib compared with 8.2 months in the placebo arm, niraparib
maintenance prolonged PFS compared with placebo in this subanalysis. In the
patients under the age of 65, the median PFS was 13.9 months with niraparib
versus 8.2 months with placebo (HR, 0.61; 95% CI, 0.47-0.81). Patients aged 65
or older had a median PFS of 13.7 months with niraparib versus 8.1 months with
placebo (HR, 0.53; 95% CI, 0.39-0.74). In the 75 years of age or below group,
niraparib led to a median PFS of 13.8 months compared with placebo, which had a
median PFS of 8.2 months (HR, 0.62; 95% CI, 0.50-0.77). Finally, in patients
aged 75 of older, the median PFS was 13.8 months with niraparib versus 5.6
months with placebo (HR, 0.37; 95% CI, 0.17-0.81).
Both ages groups were
similar in terms of the number percentage of treatment-emergent adverse events
(TEAEs) observed. The most common treatment-emergent TEAEs were anemia,
leukopenia and hypertension. Notably, patients aged 65 years or older
experienced a small increase in thrombocytopenia during treatment as did those
aged 75 years of age or older. The rates of ≥3 TEAEs were also similar between
the age groups.
The innovaTV 204/GOG-3023/ENGOT-cx6 Study
Results from the
single-arm, multicenter, international phase 2 study innovaTV were presented
during ESMO by Robert Coleman, MD, FACOG, FACS, chief scientific officer of
The US Oncology Network. The result of the study
was that treatment with tisotumab vedotin led to antitumor activity in patients
with previously treated recurrent or metastatic cervical cancer.3
“We basically
confirmed the responses that we saw in the first-in-human phase 1 and 2 study
with a 24% response rate,” Coleman told Targeted Oncology.
“Importantly, 7% of
those patients had complete response, which, for those of who have treated this
disease, these are not common findings,” he added.
As Coleman shared, the
objective response rate observed in the trial was 24% (95% CI, 15.9%-33.3%),
with complete responses in 7% of the population, partial respondes in 17%, and
stable disease in 49%. In terms of PD, 24% of patients progressed on treatment.
The median duration of response observed with tisotumab vedotin was 8.3 months
(95% CI, 4.2 to not reached). Notably, the treatment also led to a decrease in
target lesion size in 79% of the patients who received tisotumab vedotin when
compared with their baseline measurements.
Among the confirmed
responders, the median time to response was 1.4 months (range, 1.1-5.1). It was
also noted during Coleman’s ESMO presentation that responses were seen across
the subgroup populations explored, regardless of tumor histology, lines of
prior therapy, or responses to prior treatment.
The median PFS
achieved with tisotumab vedotin was 4.2 months (95% CI, 3.0-4.4). At 6 months,
the PFS rate was 30% (95% CI, 20.8%-40.1%). The median overall survival with
the agent was 12.1 months (95% CI, 9.6-13.9) and the 6-month OS rate was 79%
(95% CI, 69.3%-85.6%).
Treatment-related AEs
(TRAEs) occurred in greater than 10% of the study population. The majority of
the (TRAEs) observed in this study were grade 1 and 2 in severity. The most
TRAEs of any grade were alopecia (38%), epistaxis (30%), nausea (27%),
conjunctivitis (26%), and fatigue (24%). One patient in the died as a results
of treatment-related septic shock.
Ocular, bleeding, and
neuropathy TRAEs were also assessed in the study and bleeding TRAES were most
prevalent, with grade 1 events having observed in 34% of patients. Ocular TRAEs
were the second most prevalent with grade 1 events having occurred in 25% of
patients. Finally, grade 1 peripheral neuropathy occurred in 17% of patients.
Data from this study
led to the conclusion that tisotumab vedotin is a potential new treatment
option for patients with previously treated recurrent of metastatic cervical
cancer.
References:
1. Banerjee S, Moore KN,
Colombo N, et al. Maintenance olaparib for patients (pts) with newly diagnosed,
advanced ovarian cancer (OC) and a BRCA mutation (BRCAm): 5-year (y) follow-up
(f/u) from SOLO1. Presented at: 2020 ESMO Virtual Congress; September 19-21,
2020. Virtual. Abstract 811M0.
2. Valabrega G, Pothuri
B, Oaknin A, et al. Efficacy and safety of niraparib in older patients (pts)
with advanced ovarian cancer (OC): Results from the PRIMA/ENGOT-OV26/GOG-3012
trial. Presented at: 2020 ESMO Virtual Congress; September 19-21, 2020;
Virtual. Abstract 819P.
3. Coleman RL, Larusso
D, Gennigens C, et al. Tisotumab vedotin in previously treated recurrent or
metastatic cervical cancer: results from the phase 2 innovaTV
204/GOG-3023/ENGOT-cx6 study. Presented at: 2020 ESMO Virtual Congress;
September 19-21, 2020; Virtual. Abstract LBA32.
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