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June 01, 2019 - 06:06 pm Posted in ASCO Conference Coverage Posted in Breast Posted in Lung (includes NSCLC, SCLC, Mesothelioma) Posted in Ovarian Posted in Stomach (Gastric) Cancer comments0 Comments

Several late-breaking studies made a splash today at the 2019 American Society of Clinical Oncology (ASCO) Annual Meeting. During the press conference this morning, results from the phase III MONALEESA-7 and KEYNOTE-062 trials were presented as well as long-term survival data from the KEYNOTE-001 trial. In the afternoon, a poster session featured a late-breaking study about the impact of the Affordable Care Act (ACA) in ovarian cancer.

Adding Ribociclib to Endocrine Therapy Improves Survival (Abstract LBA1008)

The addition of ribociclib, an oral CDK 4/6 inhibitor, to frontline endocrine therapy significantly extended overall survival (OS) for premenopausal women with advanced hormone receptor-positive/HER2-negative breast cancer, according to data from the phase III MONALEESA-7 trial.

Participants (N=672) were randomly assigned to received endocrine therapy plus ribociclib or endocrine therapy plus placebo. At a median follow-up of 34.6 months, 35% of patients in the ribociclib arm and 17% in the placebo arm were still receiving the assigned treatment.

The median OS was not yet reached for the ribociclib arm and 40.9 months for the placebo arm, resulting in a 29% relative reduction in risk of death for the ribociclib arm (HR=0.712; 95% CI, 0.535 – 0.948; P=0.00973). At 42 months of follow-up, the estimated OS rate was higher for the ribociclib arm compared with the placebo arm (70.2% vs 46.0%).

“This is the first time a statistically significant improvement in overall survival has been observed with a CDK 4/6 inhibitor in combination with endocrine therapy in patients with hormone receptor-positive advanced disease,” said study presenter Sara A. Hurvitz, MD, Director of the Breast Cancer Clinical Research Program at UCLA Jonsson Comprehensive Cancer Center.

Pembrolizumab in Gastric Cancer May be Safer Than Chemo (Abstract LBA4007)

Compared with chemotherapy, pembrolizumab alone had similar survival and less toxicity in the first-line setting for patients with PD-L1−positive, HER2-negative, advanced gastric or gastroesophageal junction (G/GEJ) cancer in the phase III KEYNOTE-062 trial. A survival benefit with pembrolizumab was seen in patients with tumors that had high PD-L1 expression—defined as a combined positive score of at least 10.

In terms of toxicity, 54.3% of patients who received pembrolizumab had a treatment-related adverse event and 16.9% had a grade 3 or higher adverse event. In contrast, 91.8% of patients who received chemotherapy had a treatment-related adverse event and 69.3% had a grade 3 or higher adverse event.

“For patients with advanced gastric or gastroesophageal cancer, pembrolizumab should really, in many cases, replace chemotherapy as a first-line treatment for this population,” said ASCO Expert Richard L. Schilsky, MD, Senior Vice President and Chief Medical Officer of ASCO.

5-Year Survival Rates for NSCLC Leap Forward with Pembrolizumab (Abstract LBA9015)

Pembrolizumab improved 5-year survival rates for advanced non-small cell lung cancer patients (NSCLC), according to long-term data from the multicohort phase Ib KEYNOTE-001 trial. At 5 years of follow-up, 18% of trial participants (100 of 550) were still alive. By comparison, before the advent of pembrolizumab, the average 5-year survival rate for advanced NSCLC was 5.5%.

Higher PD-L1 tumor proportion score (TPS) was linked to better survival, particularly among treatment-naïve patients—29.6% with a PD-L1 TPS of 50% or greater were still alive 5 years later compared with 15.7% with a PD-L1 TPS between 1% and 49%.

Among patients who received at least 2 years of pembrolizumab treatment and were still alive at data cutoff (n=46), the 5-year OS rate was 78.6% for treatment-naïve patients and 75.8% for previously treated patients. The objective response rate was 86% for treatment-naïve patients and 91% for previously treated patients.

ACA Linked to Better Diagnosis and Treatment of Ovarian Cancer (Abstract LBA5563)

After the implementation of the ACA in 2010, women with ovarian cancer had an increased likelihood of being diagnosed at an early stage and receiving treatment within 30 days of diagnosis, a poster reported.

The study researchers used data from the National Cancer Database and assessed early stage at diagnosis (I/II vs III/IV) and time to treatment (<30 days vs ≥30 days) in women aged 21 to 64 with ovarian cancer (n=72,987) and compared that to women aged 65 or older with ovarian cancer (N=59,499). The study time period defined 2006 to 2009 as before the ACA and 2011 to 2014 as after the ACA.

A difference-in-differences (DD) approach showed a trend toward increased diagnosis among younger women (DD=1.7%; 95% CI, 0.7 – 2.7; P=0.001) and reduction in delays in treatment of 30 days or greater (DD=−1.6%; 95% CI, −0.7 to −2.7; P=0.001) after the ACA was implemented.

“As stage and treatment are major determinants of survival, these gains under the ACA may have long-term impacts on women with ovarian cancer,” concluded the investigators.

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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