Recent advances and updates in oncology and cancer drug development.
Cabozantinib Approved for RCC
The FDA approved cabozantinib as a treatment for patients with advanced renal cell carcinoma following prior antiangiogenic therapy, based on findings from the 658-patient phase III METEOR trial. After a minimum of 11 months of follow-up, median progression-free survival with cabozantinib was 7.4 months compared with 3.8 months with everolimus (HR, 0.58; 95% CI, 0.45-0.75; P <.001).
Cabozantinib also reduced the risk of death by 34% in the intent-to-treat population. Median overall survival was 21.4 months for patients receiving cabozantinib versus 16.5 months for those receiving everolimus (HR, 0.66; 95% CI 0.53-0.83; P = .0003). The median duration of treatment with cabozantinib was 7.6 versus 4.4 months with everolimus.
The confirmed response rate, as reported by the FDA in a statement, was 17% in the cabozantinib arm versus 3% in the everolimus arm. Grade 3/4 AEs occurred in 68% of patients treated with cabozantinib versus 58% in those who received everolimus.
Nivolumab Granted Breakthrough Status for Head and Neck Cancer
The FDA granted a breakthrough therapy designation to nivolumab as a potential treatment for patients with recurrent or metastatic squamous cell carcinoma of the head and neck following a platinum-based therapy. The designation was based on findings from the open-label phase III CheckMate-141 study, which demonstrated an improvement in overall survival with nivolumab versus investigator's choice of therapy.
Median OS with nivolumab was 7.5 months compared with 5.1 months with investigator's choice of therapy (HR, 0.70; 95% CI, 0.51-0.96). The 1-year OS rates were 36% with nivolumab compared with 16.6% for investigator’s choice. In the HPV-positive group, the median OS was 9.1 months with nivolumab compared with 4.4 months with investigator's choice (HR, 0.56; 95% CI, 0.32-0.99). In the HPV-negative arm, the median OS with nivolumab was 7.5 versus 5.8 months (HR, 0.73; 95% CI, 0.42-1.25).
Those with PD-L1 expression on ≥1% of cells experienced a median OS of 8.7 months with nivolumab compared with 4.6 months in the control arm (HR, 0.55; 95% CI, 0.36-0.83). In those with PD-L1 expression of <1%, the median OS was 5.7 versus 5.8 months, for nivolumab and the control arm, respectively (HR, 0.89; 95% CI, 0.54-1.45).
Palbociclib Improves PFS in Phase III Study
The phase III PALOMA-2 trial showed a significant improvement in progression-free survival for the frontline combination of palbociclib and letrozole compared letrozole alone for patients with ER-positive, HER2-negative advanced or metastatic breast cancer. The combination of palbociclib and letrozole was granted an accelerated approval in February 2015, based on the phase II PALOMA-1 study.
Data from the phase III study provide confirmation of the combination's benefits in the frontline setting. Pfizer plans to submit the data to the FDA and other global regulatory agencies for a full approval. In the phase II study, which led to approval, the median PFS with palbociclib was 20.2 versus 10.2 months for letrozole alone (HR, 0.488; P = .0004). The combination resulted in a response rate of 55.4% compared with 39.4% for the monotherapy. Findings from the phase III study will be submitted for presentation at the 2016 ASCO Annual Meeting, according to Pfizer.
Neoadjuvant T-DM1 Plus Pertuzumab Highly Effective
The combination of T-DM1 and pertuzumab was superior to the combination of paclitaxel and trastuzumab as a neoadjuvant treatment for women with HER2-positive breast cancer, according to an analysis the adaptively randomized I-SPY 2 Trial. For all HER2-positive patients, the pCR rate in the control group was estimated at 22% compared with 52% in the patients assigned to T-DM1/pertuzumab.
This represented a probability that T-DM1/pertuzumab was superior to paclitaxel/trastuzumab of 99.5%. Additionally, the probability that the T-DM1 regimen would be successful in a subsequent phase III trial was 94%. Among HR-positive patients, estimated pCR rates were 17% and 46% for control and T-DM1, respectively, with a 99% probability that T-DM1/pertuzumab was superior to control in this subgroup, and a 93% probability of success in phase III.
The toxicity profiles favored the T-DM1/pertuzumab combination versus paclitaxel/trastuzumab, with hypertension, neuropathy, and alopecia occurring much less frequently in patients assigned to T-DM1/pertuzumab. Based on the findings from the study, the T-DM1 combination should now advance into a phase III study.