January 2015 Edition Vol.9, Issue 1

Phase 3 Hits and Misses for 2014

Phase 3 Hits and Misses of 2014

By Nancy Ciancaglini

We conducted an informal OBR ‘audit’ based on our news archives of phase 3 cancer trial results announced this past year and were amazed at how many headlines we had. Then the tough question was: Which winners and losers make the cut for our list?  Excuse us if we didn’t include every one of your most memorable late-stage trials in our round-up below—for one thing, we tried to include a variety of cancer types. We’ve included a total of 30 hits and misses, and have included some honorable mentions in each category too.  


1) Two years follow up of the AETHERA study (n=327) showed 65% of “high risk” Hodgkin lymphoma patients receiving Seattle Genetics’ Adcetris® (brentuximab vedotin) had no evidence of disease progression compared with 45% of patients treated with placebo. It was the first trial in lymphoma to show that adding a maintenance drug after stem cell transplant could markedly improve patient outcomes. (Dec. 6, 2014)

2) In the large ASPIRE study (n=792), patients with relapsed multiple myeloma had a 9-month improvement in progression-free survival (PFS) when Amgen’s Kyprolis® (carfilzomib) was added to a standard two-drug regimen of Revlimid® (lenalidomide) and dexamethasone (KRd) compared with Revlimid and dexamethasone (Rd) alone. (Dec. 6, 2014)

3) The CheckMate -066 study (n=418), which compared Opdivo™ (nivolumab) with the chemotherapy dacarbazine (DTIC) in patients with treatment naïve BRAF wild-type advanced melanoma, was the first time a PD-1 immune checkpoint inhibitor showed a survival benefit in a randomized phase 3 trial. Opdivo demonstrated superior overall survival versus dacarbazine with a one-year survival rate of 73% versus 42% and a 58% decrease in the risk of death. (Nov. 16, 2014)

4) The coBRIM study (n=495) combined the BRAF inhibitor Roche/Plexxikon’s Zelboraf® (vemurafenib) with the Roche/Exelixis investigational MEK inhibitor cobimetinib in patients with BRAF-mutation positive advanced melanoma.  Patients in the combination arm showed 9.9 months of PFS compared with 6.2 months for those in the Zelboraf plus placebo arm. Experts said the combination of a BRAF with a MEK inhibitor should become the new standard of care for first-line therapy in this patient population. (Sept. 29, 2014)

5) In CHECKMATE -037 (n=370), Bristol-Myers Squibb presented the first phase 3 results for a PD-1 immune checkpoint inhibitor, Opdivo, versus investigator’s choice chemotherapy (ICC) in patients with advanced melanoma who were previously treated with Yervoy® (ipilimumab).  The objective response rate (ORR) was 32% in Opdivo treated patients and 11% in the reference arm of chemotherapy-treated patients (32% of patients saw their tumors shrink versus 11% of those treated with conventional chemotherapy drugs).  The duration of response was also much longer for those patients in the Opdivo arm. (Sept. 29, 2014) 

6) Final survival results announced from the CLEOPATRA study (n=808) showed that adding Perjeta®  (pertuzumab) to Herceptin® (trastuzumab) and docetaxel chemotherapy extended the lives of women with previously untreated HER2-positive metastatic breast cancer (MBC) by 15.7 months compared with Herceptin and chemotherapy (median OS: 56.5 vs. 40.8 months).  Experts hailed the results as “a new paradigm” for the treatment of first-line HER2-positive MBC. (Sept. 28, 2014)

7) In the 1,000-patient global RAISE study, Eli Lilly and Co.’s Cyramza® (ramucirumab) plus chemotherapy (FOLFIRI) prolonged the survival of patients with metastatic colorectal cancer (mCRC) who had previously failed to benefit from Avastin® (bevacizumab) and other first-line treatments. There was also a statistically significant improvement in progression-free survival in the ramucirumab-plus-FOLFIRI arm compared to the placebo-plus-FOLFIRI arm.  Data from the trial will be presented at a 2015 scientific meeting. (Sept. 12, 2014)

8) Puma Biotechnology’s stock soared as its experimental breast cancer drug neratinib met its main goal in the ExteNET trial (n=2,821) when it was used as an adjuvant treatment in women with early stage HER2-positive breast cancer who had first been treated with Herceptin.  Neratinib showed a statistically significant improvement in disease-free survival of 33% versus patients on placebo. (July 22, 2014)

9) In the RESPONSE trial (n=222) of Novartis’ Jakavi® (ruxolitinib) in patients with polycythemia vera (PV), nearly half of the ruxolitinib-treated patients had a 50% or more reduction in debilitating PV symptoms compared to 5% on best available therapy.  Seventy-seven percent of patients on ruxolitinib versus 20% on best available therapy achieved hematocrit control or spleen reduction, key treatment goals in PV, a rare blood cancer. (June 3, 2014)

10) At ASCO, results of a study of 768 patients with relapsed or relapsed/refractory multiple myeloma found those taking Novartis’ LBH589 in combination with Velcade® (bortezomib) and dexamethasone went an extra four months on average without a worsening of the disease, compared with those taking bortezomib and dexamethasone alone. (June 2, 2014)

11) A joint analysis of data from the TEXT and SOFT trials presented at ASCO showed that post-surgery (adjuvant) exemestane was more effective at preventing breast cancer recurrences than tamoxifen when given with ovarian function suppression in young women with hormone receptor-positive, early breast cancer, reducing the relative risk of developing a recurrent cancer by 28%. (June 1, 2014)

12) In the REVEL study (n=12,530), the addition of Lilly's Cyramza to standard chemotherapy reduced the risk of death by 14% compared with standard chemotherapy alone in NSCLC patients no longer responding to initial, or first-line therapy. (May 31, 2014)

13) Johnson & Johnson/Pharmacyclics’ blood-cancer drug Imbruvica® (ibrutinib) reduced the risk of dying by 57% and reduced the risk of tumor progression by 80% compared to GlaxoSmithKline's Arzerra® (ofatumumab) when used to treat elderly patients with relapsed chronic lymphocytic leukemia (CLL) in results from RESONATE (n=391). (May 30, 2014)

14) Merrimack Pharmaceuticals said the combination of its investigational injectable drug, MM-398, and two others (5-fluorouracil, or 5-FU, and leucovorin) showed an overall survival of 6.1 months, compared with 4.2 months shown by the other two drugs alone in a trial of patients with metastatic pancreatic cancer who had already been treated with gemcitabine. (May 1, 2014)

15) In the PREVAIL trial (n=1700), Medivation/Astellas Pharma’s Xtandi® (enzalutamide) reduced the risk of death by 29% compared with placebo in men with chemotherapy-naïve metastatic prostate cancer that progressed despite androgen deprivation therapy. In the other co-primary endpoint of the study, radiographic progression-free survival (rPFS), Xtandi reduced the risk of radiographic progression by 81%. (Jan. 29, 2014) 

Hits—Honorable Mentions:

  • COMBI-v, Roche/Plexxikon’s Zelboraf® (vemurafenib) plus GlaxoSmithKline’s Tafinalar® (dabrafenib) and Mekinist® (trametinib) in BRAF-mutation positive melanoma (Sept. 29, 2014)
  • ROMANA 1 and ROMANA 2, Helsinn Group’s anamorelin in cancer cachexia (Sept. 27, 2014) 
  • LUX-Lung 3 and LUX-Lung 6, Boehringer Ingelheim’s Gilotrif® (afatinib) in NSCLC (June 2, 2014)
  • SQUIRE, Lilly’s necitumumab (IMC-11F8) in NSCLC (May 14, 2014)
  • Tesaro’s rolapitant in chemotherapy-induced nausea and vomiting (CINV) (May 12, 2014)
  • PROFILE 1014, Pfizer’s Xalkori® (crizotinib) in ALK-positive advanced non-squamous NSCLC (March 25, 2014)

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