AstraZeneca PLC's failed Mystic trial cast a long shadow over second-quarter earnings, spawning more questions than answers on what the future holds for immuno-oncology.

Analysts, however, see the trial outcome as just a bump in the road and await the full results expected sometime in the first half of 2018.

In the Mystic trial, a combination of two types of treatments that fight cancer by boosting the immune system failed to beat the existing standard of care for treating a type of lung cancer called non-small cell lung cancer, or NSCLC. The combination, which included Imfinzi, a drug that blocks a protein on the surface of tumor cells called PD-L1, and tremelimumab, which targets another protein called CTLA-4, was not any better than chemotherapy in preventing the cancer from progressing.

During AstraZeneca's conference call on July 27, CEO Pascal Soriot said the trial will continue to assess the drugs' impact on overall survival despite the setback in progression free survival.

"We were, of course, disappointed by today's Mystic progression free survival readout, and we now have to wait for the overall survival data in the first half of 2018," Soriot said during the earnings call.

The trial's topline results were released early on July 27 and the news sent shares toppling 15% at market open.

Analysts quizzed the biggest players in the field — Pfizer Inc., Merck & Co. Inc. and Bristol-Myers Squibb Co., among others — about the impact the results might have on their development plans for similar drugs and the vast array of immuno-oncology combinations being studied. None of the companies hinted at changes, although they stressed the dynamic and fast-moving nature of the research.

"These developments underscore that the field is still in the very early stages of fully understanding how to exploit and optimize the power of immuno-oncology," Regeneron Pharmaceuticals Inc.'s President and Chief Scientific Officer George Yancopoulos said on the company's conference call.

"While the Mystic results are important data, and we look forward to seeing more, it's very difficult to read across trials," Bristol-Myers CEO Giovanni Caforio said during the July 27 earnings call.

"I think Mystic certainly indicated that the immuno-oncology [combination] may be more problematical in the near term. It certainly, I think, reinforces the value of PD-L1 franchises and where they stand in the different therapies, in which order they stand," Pfizer Chairman and CEO Ian Read said.

The U.S.-based drugmaker is developing a PD-L1 inhibitor drug called Bavencio with Merck KGaA. Inhibitor drugs target immune checkpoints such as PD-L1 and CTLA-4 to prevent cancer cells from downregulating and hiding from the body's immune system.

Other similar inhibitor drugs are Bristol-Myers' PD-1 inhibitor Opdivo, which is the first immunotherapy approved by the U.S. Food and Drug Administration to treat lung cancer; Merck & Co.'s Keytruda; and Roche Holding AG's Tecentriq.

AstraZeneca's Mystic trial, however, is the first phase 3 immuno-oncology combination study to have failed one of its endpoints. A phase 3 lung cancer trial for Keytruda in combination with chemotherapy is still underway and is expected to be completed by September.

Too soon to tell

As full results of the trial have not yet been published, analysts said it was too soon to tell what it meant for the immuno-oncology field.

"It's hard to make conclusions for the whole immuno-oncology landscape without looking at the [full] data," said Khurram Nawaz, a director of oncology at research and consulting company Decision Resources Group.

"A lot of people believed [Imfinzi] was dead in the water at this point. I can't help but feel it's a little too early to say that," said Dustin Phan, an analyst at Datamonitor Healthcare.

"If we look at other PD-1/PD-L1 inhibitors in NSCLC — Opdivo in its second-line study, and Tecentriq in its second-line study — both failed to demonstrate a progression free survival advantage over chemotherapy. Both ended up getting approved on overall survival," he said.

For a late stage lung cancer approval, Imfinzi will need to meet its overall survival endpoint, which is considered a more reliable indicator of efficacy.

"From a broader standpoint, it's kind of the gold standard," said Phan. "I think progression free survival is a bit trickier … [it's] also a little hard to measure. It's not always clear when you can say a patient has progressed or not."

Also, other drugs may face similar failures, Nawaz said.

Bristol-Myers in fact reported Aug. 15 that one of its Checkmate trials for the Opdivo-Yervoy combination failed to improve progression-free survival for kidney cancer patients.

"It's probably not the first failure we'll see. There's bound to be other setbacks because there are so many combinations being tested," he said. "It's really hard to see where the field is going to go."

"In many ways I think it shows there's probably a limit to these PD-1/PD-L1 inhibitors. But at the same time, they've shown an incredible amount of growth across a variety of indications in a variety of settings," said Phan.

"If this is a setback, it's a rather minor one for PD-1/PD-L1 inhibitors as a whole," Phan added.