Dr. Vishwanath Sathyanarayanan, a noted Medical Oncologist provides key takeaways from prominent breast and ovarian cancer trials and studies relevant to Indian practice, presented at European Society of Medical Oncology Clinical Congress this year. 

Breast Cancer

PALOMA-3 trial

PALOMA-3 is probably the most important trial (relevant to Indian patients) presented at ESMO 2018. Cyclin-dependent kinase (CDK) 4/6 inhibitor palbociclib in combination with fulvestrant achieves an improvement in overall survival in patients with hormone receptor positive (HR+) human epidermal growth factor receptor-2 negative (HER2-) advanced breast cancer that has relapsed or progressed on hormonal therapy, according to the final analysis of overall survival results from the PALOMA-3 study.

The final analysis assessed overall survival (OS), a key secondary endpoint of PALOMA-3, after a median follow-up of 44.8 months in 521 patients with HR+/HER2- advanced breast cancer.

Finding: The median overall survival improved by 6.9 months with palbociclib plus fulvestrant (median OS 34.9 months, 95% confidence interval [CI] 28.8-40.0) compared to placebo plus fulvestrant (median OS 28.0 months, 95% CI 23.6-34.6, p=0.043).

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Short-HER trial

The Short-HER study randomised 1,254 patients with HER2-positive early breast cancer to either 9 weeks or 1 year of treatment with trastuzumab, with both groups also receiving chemotherapy. It was a negative trial and did not meet the noninferiority. At ESMO 2018, the authors presented data of certain subsets which was interesting.

Findings:

1. Low-risk (pathologic tumor size [pT] < 2 cm and N0) and intermediate-risk (pT < 2 cm and any N category) patients achieved a similar 5-year disease-free survival with a 9-week course of trastuzumab (88%) as with 1 year (89%; hazard ratio [HR] = 1.02, 95% confidence interval [CI] = 0.78–1.33).
2. The patients' risk of cardiac events was nearly three times lower (4.5% vs 12.8%, relative risk = 2.88, 95% CI = 1.85–4.47).

However, the study was underpowered to draw reasonable conclusions.

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IMpassion 130 trial

Immunotherapy is being used in several cancers in India and finally, we have some good news in metastatic triple negative breast cancer (mTNBC). The IMpassion 130 was a phase III trial which enrolled 902 patients with TNBC who had not received prior treatment for metastatic disease. Patients were randomly randomised to receive standard chemotherapy (nab-paclitaxel) plus the PDL1 blocker-atezolizumab, or to standard chemotherapy plus placebo. The median follow-up was 12.9 months.

Findings:

1. In the entire study population, the median progression-free survival was 7.2 months with the combination and 5.5 months with chemotherapy alone (hazard ratio [HR] = 0.80, P = .0025).
2. In the PD-L1–positive group, the median progression-free survival was 7.5 months with the combination and 5.0 months with chemotherapy alone (HR = 0.62, P < .0001).
3. In patients with PD-L1–positive tumors, the median overall survival was 25.0 months with the combination compared to 15.5 months with standard chemotherapy alone (HR = 0.62).

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Lisinopril or Carvedilol for preventing cardiotoxicity in HER2-Positive Breast Cancer

Munster and colleagues presented the results of a very practical prospective study on the prophylactic use of angiotensin-converting enzyme inhibitors or beta blockers may prevent cardiotoxicity associated with chemotherapy and trastuzumab. The rates of pre-specified cardiotoxicity and trastuzumab interruptions were evaluated in 468 patients with early-stage HER2 positive breast cancer treated with one year of trastuzumab. Patients were randomised to simultaneously receive either the ACE inhibitor, lisinopril, or beta-blocker, carvedilol, or placebo and were stratified by anthracycline use.

Finding: The authors noted that in the arm which had trastuzumab and anthracyclines, the interventions reduced trastuzumab interruptions, lesser cardiac event, and better cardiotoxicity-free survival.

However, the cardiac events for patients treated with non-anthracycline containing regimens were similar for all groups with no difference in the number of trastuzumab interruptions.

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HOBOE-2 trial

It is the first study to test the adjuvant treatment of zoledronic acid plus letrozole and the improvement in disease-free survival compared to tamoxifen in premenopausal women with hormone receptor-positive (HR) early breast cancer.

Finding: Disease-free survival was significantly improved in patients randomised to zoledronic acid plus letrozole compared to those treated with tamoxifen, with an absolute advantage of 8% in 5-year DFS.

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Ovarian Cancer

Phase III SOLO-1 trial

The trial studied the use of PARP inhibitor, olaparib, used as a maintenance for 24 months in newly-diagnosed, advanced BRCA-mutated (BRCAm) ovarian cancer who were in complete or partial response following 1st-line standard platinum-based chemotherapy.

Findings:

1. Improvement in progression-free survival (PFS) was seen for olaparib compared to placebo, reducing the risk of disease progression or death by 70% (HR 0.30 [95% CI 0.23-0.41], p<0.001).
2. At 41 months of follow-up, the median PFS for patients treated with olaparib was not reached compared to 13.8 months for patients treated with placebo.

Disclaimer- The views and opinions expressed in this article are those of the author's and do not necessarily reflect the official policy or position of M3 India.

The writer, Dr. Vishwanath Sathyanarayan is a Medical Oncologist from Apollo Hospitals, Bangalore with a fellowship from MD Anderson Cancer Center.