May 29, 2019 - 11:05 am Posted in ASCO Conference Coverage Posted in Breast Posted in Cervical Posted in Immuno-oncology (includes cancer vaccines) Posted in Liver (includes HCC, Billiary Tract) Posted in Lung (includes NSCLC, SCLC, Mesothelioma) Posted in Multiple Myeloma Posted in Pancreatic Posted in Prostate Posted in Stomach (Gastric) Cancer 0 Comments
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
As the Genitourinary Cancers (GU) Symposium gets under way in San Francisco February 13-16 2019, at a pre-meeting Presscast, ASCO experts singled out three abstracts to be presented at the meeting as of special interest: two on prostate cancer and one on kidney cancer. As would be expected, these three abstracts are just the tip of the iceberg among many important studies to be discussed at the 3-day meeting.
Prostate Cancer – Racial Disparity in Survival?
A large retrospective study to be presented at the meeting suggests that African-American men with chemotherapy-naïve metastatic castrate-resistant prostate cancer (mCRPC) have improved survival on the newer androgen-directed therapies abiraterone or enzalutamide compared with Caucasians (Abstract 212). This is the first study to suggest a survival benefit for both drugs in African-American men, and further study is needed to validate this finding.
“We’ve historically seen that prostate cancer is more common, more aggressive, and more lethal in African Americans compared with men of other racial groups. Balancing against other health-related risks, we found that treatment with newer hormonal medicines led to a significantly greater survival for African-American men in this analysis, compared with white men,” said lead study author Megan Ann McNamara, MD, Assistant Professor of Medicine, Duke University School of Medicine, Durham, NC.
“These findings provide important evidence that African-American men with metastatic prostate cancer, who have long had among the highest incidence and poorest outcomes of this disease, may now have better survival when treated with newer prostate cancer medications as compared with other men,” said ASCO Expert Robert Dreicer, MD, moderator of the Presscast.
The study was based on the Veterans Health Administration database from April 1, 2013 to March 31, 2018. Researchers identified 787 African American men and 2123 Caucasians aged 18 or older with prostate cancer and disease progression after surgical or medical castration; all men received either abiraterone or enzalutamide, but no chemotherapy. Patients were followed until death or disenrollment in their VA health plan. Median follow-up was 570 days for African-American men and 561 days for Caucasians.
African-American men were more likely than Caucasians to have the following co-morbidities: hypertension (77.1% versus 67.1%, respectively, P<.0001); type II diabetes (38.1% versus 29.3%, respectively, P<.0001); and liver damage or abnormality (8.8% versus 5.2%, respectively, P=.0003).
In an analysis adjusted for demographic and clinical characteristics, median overall survival was 30 months for African-American men compared with 26 months for Caucasians.
“This study was conducted in men with access to care through a single-payer system. The evidence suggests that African-American men have improved survival on standard of care treatments. Prospective trials are needed to validate these findings,” Dr. McNamara said.
Prostate Cancer – Radioligand Therapy
A novel approach using a tumor-specific radioligand therapy that binds to prostate specific membrane antigen (LuPSMA) had a strong showing in an expanded Phase II study of men with metastatic castrate-resistant prostate cancer (mCRPC) who progressed on standard therapies (Abstract 228). The study showed high rates of PSA response with low toxicity, and high response rates were also seen in men who subsequently progressed on LuPSMA and were treated with further LuPSMA, the authors said.
Moreover, men treated with LuPSMA lived a median of 13.3 months after treatment, surpassing expected survival of 9 months for this stage of disease.
The study, the first prospective study of LuPSMA, is based on an expanded cohort of 50 patients; results in the first 30 patients treated were reported previously in The Lancet Oncology in June of 2018. The present study confirms earlier findings using LuPSMA, and two randomized controlled trials will compare LuPSMA versus cabazitaxel and LuPSMA versus best standard of care, respectively.
“For men with localized prostate cancer, brachytherapy, or radioactive seeds implanted by needle directly into the tumor, as well as external beam radiotherapy, have been effective forms of treatment. However, for men in this trial with cancer cells spread throughout the body, LuPSMA provides a new approach to a form of the disease that has been difficult to treat,” said lead author Michael Hofman, MBBS, professor of nuclear medicine at the Peter MacCallum Cancer Centre, Melbourne, Australia.
“In this trial, we treated men who would have otherwise been directed to palliative care. It’s exciting to see that LuPSMA can potentially offer benefits for many men with these very aggressive cancers, with few side effects and significant improvements in quality of life. Importantly, we saw continued benefit with LuPSMA retreatment in some men whose cancer progressed,” Dr. Hofman said.
Patients enrolled in the Phase II study were diagnosed with PSMA-positive mCRPC by upfront PET scan and were treated with up to 4 cycles of LuPSMA every 6 weeks. The primary endpoints were PSA response and toxicity. In the 50 patients enrolled in the trial, median PSA doubling time was 2.6 months. The majority of patients received prior treatment (docetaxel, 84%; cabazitaxel (48%), and abiraterone or enzalutamide (90%).
A PSA decline of >50% was observed in 32 of 50 patients (64%), including 22 patients (44%) with a PSA decline >80%. Among 27 patients with soft tissue disease at baseline, 56% had a partial or complete response according to RECIST criteria. Fourteen patients who progressed on LuPSMA received a median of 2 more cycles of LuPSMA; PSA >50% decline was observed in 9 patients (64%).
Adverse events were similar to those reported earlier in 30 patients: transient grades 1-2 dry mouth (68%), nausea (48%),and fatigue (36%).
Grades 3 to 4 toxicities were thrombocytopenia and anemia (10% for each). Median PSA progression-free survival was 6.9 months and median overall survival was 13.3 months.
“Survival rates are low for patients with prostate cancer that has spread to distant parts of the body, and providing effective treatments for this type of cancer has been an ongoing challenge. For this group of patients in dire need of new options, using an entirely new approach provides hope that we can start to change their outcomes,” said ASCO Expert Robert Dreicer, MD, Presscast moderator.
Immunotherapy Combo in RCC
Immunotherapy is making inroads in the treatment of metastatic renal cell carcinoma (mRCC), according to promising results of the phase III KEYNOTE-426 study. The global, open-label phase III study demonstrated the superiority of the combination of pembrolizumab plus axitinib versus standard of care sunitinib as first-line therapy for mRCC (Abstract 543).
Pembrolizumab plus axitinib showed significant improvements in overall survival (OS), progression-free survival (PFS), and objective response rate (ORR) at a median follow-up of 12.8 months (P<.0001 for all three comparisons with suninitib). Twelve-month OS was 89.9% for the combination versus 78.3% for sunitinib (P= .0001). Median PFS was 15.1 months versus 11.1 months, respectively, and ORR was 59.3% versus 35.7%, respectively. Duration of response was not yet reached for the combination therapy arm versus a median of 15 months for sunitinib.
“These results are exciting. By adding pembrolizumab to a VEGF-targeted TKI we are seeing powerful anticancer responses, including improved survival, and importantly, results are seen across broad subgroups of patients. These data suggest that pembrolizumab plus axitinib should be a new standard of care for this population, in my opinion,” said lead author Thomas Powles, MD, Professor of Urology Oncology, Barts Cancer Institute, London, U.K.
Following promising results of a phase Ib study, the phase III KEYNOTE-426 trial randomized 861 patients with clear-cell RCC and no previous systemic therapy for mRCC to either arm. Pembrolizumab was given 200 mg IV every 3 weeks for a maximum of 35 cycles plus oral axitinib 5 mg b.i.d. versus oral sunitinib 50 mg every day on a 4 week on/2 week off schedule. Patients were treated until disease progression, unacceptable toxicity, or investigator’s decision.
“There have been few significant advances in treating this advanced form of disease. These findings may help provide an important new option for patients with mRCC,” said ASCO Expert Robert Dreicer, MD, Presscast moderator.
By Adrian Barfield, President, Medallion Healthcare