The OBR Blog

Today, four plenary sessions dropped at the 2019 American Society of Clinical Oncology (ASCO) Annual Meeting featured results from three phase 3 trials: ENZAMET, ANNOUNCE, and POLO as well as encouraging data about the impact of Medicaid expansion under the Affordable Care Act (ACA).

Medicaid Expansion Closes Racial Disparities Gap (Abstract LBA1)

When the ACA was implemented in 2010, states were permitted to expand Medicaid access. A retrospective study found that states that expanded Medicaid had a reduction in racial disparities in time to cancer treatment.

Using data from electronic health records, researchers observed timely treatment (ie, treatment initiation within 30 days of diagnosis) for adult patients younger than 65 with a diagnosis of advanced or metastatic cancer. The study population included more than 30,000 patients, and depending on the Medicaid expansion status of the state in which they lived, patients were labeled as participating in Medicaid expansion or not.

When Medicaid was not expanded, a significantly lower percentage of African American patients received timely treated compared with white patients (43.5% vs 48.3%; P<0.001). When Medicaid was expanded, this racial disparity gap did not exist (49.6% vs 50.3%; P=0.63).

“The disparities disappeared under the expansion,” summed up study presenter Amy Davidoff, PhD, Yale University.

Enzalutamide for the Win in Metastatic Prostate Cancer (Abstract LBA2)

Enzalutamide outperformed standard non-steroidal anti-androgens for men with metastatic hormone-sensitive prostate cancer, according to data from an interim analysis of the randomized, phase 3 ENZAMET trial.

Patients (n=1,125) received a testosterone-suppressing medicine followed by treatment with enzalutamide or a standard of care non-steroidal anti-androgen: bicalutamide, nilutamide, or flutamide.

For the overall patient population, the 3-year overall survival (OS) rate was 79% for men treated with enzalutamide; 72% for men treated with bicalutamide, nilutamide, or flutamide. This resulted in a 33% reduced likelihood in risk of death for men treated with enzalutamide (HR=0.67; 95% CI, 0.52-0.86; P=0.002).

In particular, an OS benefit for enzalutamide was seen among men with high volume disease (HR=0.74; 95% CI, 0.55-1.01) or no planned early docetaxel (HR=0.51; 95% CI, 0.36-0.73), but not for those with planned early docetaxel (HR=0.90; 95% CI, 0.62-1.31).

“There is a delay in progression with an improvement in overall survival, but there is toxicity,”  cautioned study presenter Christopher Sweeney, MBBS, a medical oncologist at the Lank Center for Genitourinary Oncology, Dana-Farber Cancer Institute. “Ezalutamide actually increased the docetaxel-related toxicity.”

Olaratumab Flops in Phase 3 for Advanced Soft Tissue Sarcomas (Abstract LBA3)

Despite encouraging survival data in the previous phase 1b/2 trial, olaratumab in combination with doxorubicin failed to improve survival in patients with advanced soft tissue sarcomas in the phase 3 ANNOUNCE trial. Olaratumab in combination with doxorubicin was granted accelerated approval in 2016, but in light of the ANNOUNCE trial results, olaratumab is in the process of being withdrawn from the market.

No clear reason was offered for the failure of olaratumab in the phase 3 trial, but a few possibilities were floated, such as the control arm having a particularly high OS and not limiting study entry to treatment-naïve patients.

Offering a partial explanation for the initial survival benefit seen in the early-phase trial, study discussant Jaap Verweij, MD, PhD, Erasmus University Medical Center, said, “A critical issue in phase 2 studies, certainly in a group of diseases as heterogenous as soft tissue sarcomas, are small numbers of patients.”

Olaparib Hits its Target in BRCA-Positive Metastatic Pancreatic Cancer (Abstract LBA4)

Maintenance therapy with olaparib, a PARP inhibitor, after first-line, platinum-based chemotherapy extended progression-free survival (PFS) for patients with germline BRCA-positive metastatic pancreatic cancer, according to the results of the phase 3 POLO trial. Final OS results are still maturing.

The trial included metastatic pancreatic cancer patients with a BRCA1 or BRCA2 germline mutation who received chemotherapy for at least 16 months and then were randomly assigned maintenance therapy with either olaparib or placebo.

The median PFS was 7.4 months for the olaparib arm and 3.8 months for the placebo arm, resulting in a 47% reduced risk of progression for patients receiving olaparib (HR=0.53; 95% CI, 0.35 – 0.82; P=0.0038).

The objective response rate was 23.1% (18 of 78 patients) for the olaparib arm and 11.5% (6 of 52 patients) for the placebo arm, with two patients on olaparib achieving a complete response; both complete responses are ongoing. The median duration of response was 24.9 months for the olaparib arm and 3.7 months for the placebo arm.

“We conclude that a strategic approach of first-line, platinum-based chemotherapy followed by maintenance olaparib treatment should become a new standard of care for patients with metastatic pancreatic cancer who have a germline BRCA mutation,” said the study presenter Hedy Kindler, MD, Professor of Medicine, University of Chicago Medicine.

by Christina Bennett, MS

One of biggest challenges in attending an annual ASCO meeting is time management. With over 2,000 abstracts submitted this year and a wide variety of new drugs and therapeutic targets, ASCO 2019 will be no different.

During a webinar last week sponsored by E-Squared Communications (a Conisus company), OBR and three renowned cancer experts helped identify some of the “high impact studies” that are sure to gain a lot of attention at this year’s ASCO Annual Meeting. For those of you who missed this increasingly popular annual webinar, the experts not only covered the important data but also provided some suggestions on where to go if you happen to play hooky for a day at ASCO. Don Sharpe, President and Founder of OBR, moderated the session, and the primary areas of focus included cervical, prostate, pancreatic, breast, lung, and advanced gastric/gastroesophageal junction cancers as well as multiple myeloma and hepatocellular carcinoma (HCC).

Pending its final outcome, the first trial highlighted in the webinar could well be a practice-changing study. This phase 3 Intergroup trial (E3A06) in patients with asymptomatic intermediate- or high-risk smoldering multiple myeloma is the largest randomized trial in this setting to date. The 182 patients who participated in this study were randomized to either receive lenalidomide alone or observation, with progression-free survival (PFS) being the primary endpoint. At a median of 28 months of follow-up, the 3-year PFS rate in the lenalidomide arm seems to be numerically trending in the right direction (91% vs. 66%). This data will be highlighted in an oral abstract (8001) session on Sunday, June 2nd.

Following an interesting review of a phase 2 study highlighting the use of LN-145 tumor infiltrating lymphocytes in patients with cervical cancer, the next phase 3 study highlighted by the experts was a late-breaking abstract. This Australian and New Zealand Urogenital (ANZUP) Cooperative Group trial (ENZAMET) evaluated enzalutamide as first-line androgen-deprivation therapy for metastatic hormone-sensitive prostate cancer. The abstract LBA2 will be presented at the plenary session on Sunday, June 2nd and is sure to draw comparisons to the earlier LATITUDE study of abiraterone in this setting.

Pancreatic cancer seems to be climbing into the spotlight as well this year, as the OBR experts identified the Adjuvant Treatment in Pancreatic Cancer Study (APACT) as an important one to watch. This study evaluated nab-paclitaxel plus gemcitabine versus gemcitabine alone for patients with surgically resected pancreatic cancer. With 866 patients enrolled, this large clinical trial had a primary endpoint of disease-free survival; however, the authors noted that the overall survival (OS) results seen in this study may better support the rationale of using this combination in the adjuvant setting, especially for patients who are ineligible for FOLFIRINOX.

The PARP inhibitor olaparib was also discussed in the webinar as a potentially new therapeutic option for patients with pancreatic cancer. The phase 3 POLO trial of olaparib versus placebo as maintenance therapy in patients with germline BRCA-mutated metastatic pancreatic cancer whose disease had not progressed following first-line platinum-based chemotherapy will be highlighted during the plenary session on Sunday, June 2nd (LBA4). This study is the first positive phase 3 trial of any PARP inhibitor in germline BRCA-mutated metastatic pancreatic cancer.

Pembrolizumab was highlighted as well in two studies looking at gastric cancer and GEJ adenocarcinoma (KEYNOTE-062) and advanced HCC (KEYNOTE-240). In KEYNOTE-062, pembrolizumab met its primary endpoint by demonstrating OS noninferiority compared to chemotherapy in the intent-to-treat population. In KEYNOTE-240, pembrolizumab showed positive numerical trends but did not meet statistical significance for its co-primary endpoints of OS and PFS; however, it did show an improved response rate versus placebo (ORR 16.9% vs. 2.2%), and it will be interesting to see what impact this might have going forward.

Another important KEYNOTE study is KEYNOTE-189: Updated OS and progression after the next line of therapy (PFS2) with pembrolizumab (pembro) plus chemo with pemetrexed and platinum vs placebo plus chemo for metastatic nonsquamous NSCLC. KEYNOTE-001 is also a late-breaking abstract looking at 5-year long-term OS for patients with advanced non-small cell lung cancer treated with pembrolizumab.

There are certainly other important abstracts at this year’s ASCO Annual Meeting, but at the very least, this review should help narrow down your choices.

By Adrian Barfield, President, Medallion Healthcare

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